Category Archives: Psoriasis

Nick Stucky, MD, PhD, continued his discussion of his teams findings on rates of prescription of oral minoxidil following the publication of an article by The New York Times, noting the biggest implications of the findings.1

Stucky is vice president of research at Truveta, working also as a physician-scientist and bioengineer. Additionally, he is known for being a start-up founder, faculty teaching, and having been research director.

After having described the findings, Stucky in this interview segment first described the studys limitations in general.

One thing is that we get data from our member healthcare systems, so they provide care to a certain population, he explained. We have 17% of the US healthcare daily delivered care within our dataset, so it's quite large. But there are always potential biases if you're not actually surveying the whole US population.

Stucky also added that there may be a skew toward insured patients, for example. He added that there were certain questions by reviewers regarding whether the article led to increased prescribing for all hair loss medications.

And so we added kind of a control armwhich was another hair loss medication that wasn't mentioned in that article, Stucky explained, adding that this group had no changes in prescribing.

He then highlighted some of the biggest implications from his teams findings, noting that they did not know for sure whether the article had a direct impact on the providers or the patients who read the single media publication.

But yes, I mean, I think it definitely says that we're all human, and we all are sort of influenced by our environment, Stucky said. And certainly, this indicates that either practitioners or patients can be profoundly impacted in terms of how they interact with the healthcare system, by a single article.

Additionally, Stucky mentioned that he believes there are other important implications for his teams findings.

I think many providers probably had concerns about whether it was safe, whether there'd be any adverse effects, but those had mostly been put to rest by these handful of studies that have come out, he said. But nobody was aware of them and so by, in this case, a New York Times article, but really any other media that we're consuming, we can learn really valuable (insights).

The interview segments quotes were edited for clarity. For more information on the research described here, view the full video above.

See the article here:
Nick Stucky, MD, Phd: Implications for Media Influence on Minoxidil ... - MD Magazine

Treatment with tildrakizumab improved health-related quality of life (HRQoL) and patient-reported symptoms in those with psoriasis in a real-world setting, according to a new study published in The Journal of Dermatological Treatment.

The antiinterleukin-23 p19 monoclonal antibody is approved for treatment of adults with moderate to severe plaque psoriasis.

Psoriasis and its symptoms, which can include itch, pain and scaling, have substantial negative effects on patients QOL. Previous research shows patients report negative effects on sleep and rest, limitations on daily activities, and disruption to social interactions. Many also experience depression, anxiety or addiction.

The chronic multisystem disease manifests most noticeably as skin inflammation, the study authors said. Plaque psoriasis, the most common form of the condition, often appears on the skin of the knees, elbows, scalp, buttocks and trunk.

Of all the symptoms of psoriasis, itch has been reported to contribute the most to reductions in patients emotional well-being, sleep, and daily activity.

However, in general, the relationship between clinical treatment of psoriasis and patients HRQoL is poorly understood and may be underestimated by clinicians, the researchers wrote. There is therefore an unmet need for greater understanding of this relationship to inform the choice of therapeutic intervention.

To address the knowledge gap, the investigators carried out a phase 4 study under real-world conditions. The current research outlines results after 28 weeks of treatment with tildrakizumab.

All participants received tildrakizumab 100mg at weeks 0 and 4, and every 12 weeks thereafter. The researchers measured progress via the Psychological General Well-Being Index (PGWBI), Dermatology Life Quality Index (DLQI), and Itch-, Pain-, and Scaling-Numerical Rating Scale scores. Of the 55 enrolled patients, 53 were evaluated at week 28.

Data showed:

Just over half of patients included were male and the majority were White. The mean patient age was 48.6 years.

Despites PGWBI score improvements seen for general health and positive well-being, no statistically significant improvements were seen from baseline to week 28 for anxiety, vitality, depressed mood, and self-control.

However, the treatment did result in improvements in reported itching, pain, and scaling beginning at week 4 and these were maintained throughout the study window.

Clinical trials have often focused on the effects of skin clearance on the HRQOL of patients with psoriasis. Complete skin clearance has been associated with higher scores on measures of HRQOL compared with almost complete clearance, the authors explained.

Previous research on theimpact of the efficacy of tildrakizumab treatment has shown absolute Psoriasis Area Severity Index scores correlated with DLQI total scores.

In controlled clinical trials, strict inclusion and exclusion criteria may preclude findings from fully representing or characterizing the patient population in real-world clinical practice, the researchers said.

To date, there has been little published real-world evidence regarding HRQOL in patients with moderate to severe plaque psoriasis treated with tildrakizumab, they added.

The relatively small sample size marks a limitation to the current study, and it remains unclear whether tildrakizumab treatment may affect patients HRQOL over a longer period of time.

Additional research is recommended to further guide clinicians in choosing optimal treatment strategies to improve HRQOL in patients with moderate to severe psoriasis, the authors concluded.

Reference

Bhatia N, Heim J, Schenkel B, Vasquez JG. Quality of life and patient-reported symptoms in a phase 4, real-world study of tildrakizumab in patients with moderate-to-severe psoriasis: week 28 interim analysis. J Dermatolog Treat. Published online May 11, 2023. doi:10.1080/09546634.2023.2200872

Read more from the original source:
Tildrakizumab Linked With HRQOL Improvement in Psoriasis in a Real-World Setting - AJMC.com Managed Markets Network

1School of Medicine, University of California at San Francisco, San Francisco, CA, USA; 2Department of Dermatology, University of California at San Francisco, San Francisco, CA, USA

Correspondence: Joy Q Jin, Box 1212, Floor 01, Room 101, 2340 Sutter Street, San Francisco, CA, 94115, USA, Tel +1 415-353-7800, Fax +1 415-502-4126, Email [emailprotected]

Introduction: Psoriasis is a chronic, immune-mediated skin condition with significant detriments to physical/mental health. While systemic therapies are available for the treatment of moderate-to-severe psoriasis, patients can experience therapeutic failure, loss of efficacy, or medical contraindications that require other therapeutic options.Objective: With the recent approval of deucravacitinib, a first-in-class TYK2 small molecule inhibitor administered orally for psoriasis patients, we reviewed data from randomized controlled trials (RCTs) to synthesize its clinical utility. To our knowledge, this is the first systematic review and meta-analysis of deucravacitinib comparing its clinical efficacy to placebo in psoriasis.Methods: A literature search was conducted in PubMed (MEDLINE), Embase, and the Cochrane Central Register of Controlled Trials to identify RCTs studying deucravacitinib in human patients with moderate-to-severe psoriasis.Results: One placebo-controlled Phase II RCT and two placebo-controlled/active-comparator Phase III RCTs were included for review. Patients (N=1953) treated with deucravacitinib 6 mg daily showed marked improvement in disease severity (Psoriasis Area and Severity Index (PASI), static Physician Global Assessment (sPGA) and quality-of-life outcomes compared to patients administered comparator (apremilast) and placebo. Clinical improvement given deucravacitinib was noted for scalp psoriasis but not fingernail psoriasis. Meta-analysis (deucravacitinib, n=888; placebo, n=466) comparing rates of clearance (sPGA 0/1) demonstrated superior efficacy of deucravacitinib compared to placebo (odds ratio, 12.87; 95% confidence interval, 8.97 18.48; 2=4.08, I2=51%). Deucravacitinib was well-tolerated, with similar rate of occurrence and type of adverse events reported among patients treated with placebo or apremilast at Week 12 16. No cardiovascular events, serious infections, or lab abnormalities were noted.Conclusion: Deucravacitinib possesses good efficacy, with no report of safety concerns associated with prior JAK inhibitors used for psoriasis. Meta-analysis demonstrated deucravacitinibs superiority compared to placebo, indicating its promising clinical utility. Further studies are needed to observe long-term safety and efficacy, and to compare deucravacitinib to existing treatments.

Keywords: apremilast, deucravacitinib, meta-analysis, placebo, plaque psoriasis, systematic review

Psoriasis is a chronic inflammatory disorder of the skin and joints that affects 8 million Americans and 23% of the population globally.1 Psoriasis has a profound impact on both the physical and psychosocial health of those affected. Patients are subject to increased risk of developing comorbid systemic disease, including cardiovascular disease, diabetes, anxiety, depression, and all-cause mortality.2

A variety of therapies are available for the treatment of psoriasis, including topical medications, phototherapy, oral and biologic agents. Oral immunosuppressants such as methotrexate and cyclosporine may be highly effective for some patients, but such treatments have significant potential for adverse effects.3 For individuals with a more severe psoriatic disease course, treatment with a systemic therapy such as a biologic agent is often required. Recent advancements surrounding new targeted agents have yielded promising results; here, we review the clinical potential of deucravacitinib (ie, BMS-986165, SotyktuTM), a new oral small molecule approved by the US Food and Drug Administration (FDA) in September 2022 for the treatment of moderate-to-severe psoriasis.

The pathogenesis of psoriasis is characterized by aberrant keratinocyte differentiation and excessive growth of the epidermis, leading to the formation of erythematous patches and plaques with thick overlying scale.4 Psoriasis pathogenesis involves a complex interplay of genetic (eg, susceptibility alleles) and environmental factors, which can combine to trigger systemic inflammatory cascades leading to disease presentation.4 While psoriatic immune dysregulation is complex and not fully elucidated, T helper 17 (Th17) cells are known to be a central component that, when aberrantly activated, produce important effector cytokines acting in a positive feedback loop to recruit additional immune cells and accelerate psoriasis development.5,6

Involvement of the interleukin (IL)-23/IL17 pathway mediates psoriasis via the activation and promotion of keratinocyte proliferation.5 Cytokines like TNF-, IL-17, and IL-23 are the targets of biologic agents used in psoriasis.7,8 Many of these same cytokines, including IL-23, bind to type I and II cytokine receptors, which possess no inherent catalytic activity and must rely on Janus kinase (JAK) proteins to mediate their effects.7 Tyrosine kinase 2 (TYK2) is one of four members of the JAK family of proteins.7

JAK/STAT signaling refers to a system comprised of a dimeric transmembrane cytokine receptor, a pair of intracellular JAKs, and a family of Signal Transducers and Activators of Transcription (STATs).7 Upon binding of a cytokine to its receptor, a conformational change in the receptor proteins occur, leading to autophosphorylation of intracellular JAKs.7 This enables another conformational change leading to the phosphorylation of STATs, which then dissociate from the receptor complex before translocating to the nucleus and acting as transcription factors.7

TYK2 pairs with other JAK family members to mediate the signaling of IL-12 and IL-23 receptors, as well as type I IFN receptors; TYK2 inhibition leads to reduced Th17 cell polarization, increased suppressive functions of regulatory T cells, and additional downstream effects protective against psoriasis development.912 Given TYK2s role downstream of current biologic targets such as IL-12 and IL-23, TYK2 inhibition may serve as a promising strategy that can address existing challenges in the treatment of moderate-to-severe psoriasis.12

In September 2022, deucravacitiniban oral, first-in-class, small molecule, selective allosteric inhibitor of TYK2was approved by the FDA for the treatment of psoriasis in the U.S.13 Deucravacitinib binds to the catalytically inactive pseudokinase regulatory domain of TYK2 and stabilizes an inhibitory interaction between the regulatory and catalytic domains.13 Through this method, TYK2 is inactivated and cannot interact with other receptors to lead to downstream signal transduction.11,14 In preclinical studies, deucravacitinib was revealed to inhibit TYK2 with high selectivity and minimal off-target effects on other JAK family members,11,14 suggesting that deucravacitinib may possess an improved safety profile compared to less specific JAK inhibitors, which have been associated with hyperlipidemia, increased risk of infections, and other systemic changes.1416

Given recent FDA-approval and promising clinical data, we aimed to investigate deucravacitinibs clinical utility for the treatment of moderate-to-severe psoriasis. To our knowledge, no systematic review has been conductedhere, we performed a systematic review with meta-analysis to synthesize the findings from randomized controlled trials (RCTs) studying deucravacitinib for psoriasis.

As a review, all data used were non-identifiable and publicly available; institutional review board approval was not required at the University of California, San Francisco. The study protocol and design are reported according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2020 guidelines.17 A literature search was conducted in PubMed (MEDLINE), Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) in March 2023 using a combination of the terms (deucravacitinib OR sotyktu) AND (psoriasis).

The efficacy of new psoriasis treatments is measured in clinical trials via standardized, objective disease severity metrics, including the Psoriasis Area and Severity Index (PASI) and Physician Global Assessment (PGA).18,19 These tools utilize grading scales to stratify disease severity based on clinical characteristics including body surface area involvement and degree of erythema, induration, and scaling. Given the impact psoriatic disease has on patients psychosocial health and quality of life, concomitant assessment of these domains with tools such as the Dermatology Life Quality Index (DLQI) is appropriate and often co-reported in clinical trials or post hoc studies.19

Studies included in this review were RCTs investigating human subjects with moderate-to-severe psoriasis (thus, only Phase II trials and above, as Phase I trials were conducted in healthy participants),20 defined in clinical trials as static PGA (sPGA) 3, PASI 12, and body surface area (BSA) 10%, treated with deucravacitinib. RCTs that studied psoriatic arthritis but not psoriasis were excluded.21 Study characteristics including clinical trial name/number, number of patients, intervention dose and frequency, treatment duration, clinical efficacy, and safety outcomes were obtained using a standardized table tailored to this review.

Initial screening of studies was performed manually by two independent reviewers (J.Q.J., R.K.S.). Any queries in eligibility criteria were resolved via adjudication by an additional reviewer (W.L.). Data abstraction was performed by two independent reviewers (J.Q.J., R.K.S.). All randomized studies included for analysis were assessed for risk of bias by two independent authors (J.Q.J., R.K.S.) using the Critical Appraisal Skills Programme (CASP) checklist for RCTs.22

Primary outcomes sought for the purpose of this review included an sPGA of 0 or 1 (indicating clear or almost clear disease). Secondary outcomes included an sPGA of 0, a 75%, 90%, or 100% improvement in the PASI score (ie, PASI 75, PASI 90, or PASI 100), a DLQI score of 0 or 1, scalp-specific PGA (ss-PGA) of 0 or 1, and a PGA of Fingernail Psoriasis (PGA-F) of 0 or 1. The final endpoint was determined to be Week 1216, as all included studies reported efficacy measures within this timepoint.

Meta-analysis was performed using the Cochrane Review Manager 5.4 application comparing the sPGA 0/1 rates of deucravacitinib versus placebo. Only data from patients receiving the FDA-approved dose of deucravacitinib (6 mg per day) or placebo were included for meta-analysis. An odds ratio (OR) was calculated using the Mantel-Haenszel fixed-effects method, which was chosen over the Peto method as the latter is better suited for rare event occurrences.23 Significance of heterogeneity was assessed using the 2 test (P<0.1 set as statistically significant) and presented as the I2 test (I2>50% indicates significant heterogeneity, I2<25% indicates non-significant heterogeneity).

Following the application of inclusion and exclusion criteria (PRISMA diagram shown in Figure 1), three RCTs were included for review, including one Phase II placebo-controlled trial (NCT02931838)24 and two Phase III placebo-controlled and active-comparator (apremilast) RCTs (POETYK PSO-1, POETYK PSO-2).25,26 The three RCTs were composed of a total of 1953 patients with moderate-to-severe psoriasisincluding 1065 treated with deucravacitinib, 422 treated with apremilast, and 466 who received placebo. Overall, deucravacitinib patients showed marked improvement in disease severity and quality-of-life outcomes compared to apremilast and placebo groups; deucravacitinib patients with scalp psoriasis demonstrated marked improvement compared to apremilast and placebo groups, but improvements in fingernail psoriasis measures were not significant (Table 1). The risk of bias assessment of all studies is presented in Table 2.

Table 1 Clinical Outcomes Reported in Deucravacitinib Randomized Controlled Trials for Moderate-to-Severe Psoriasis

Table 2 Risk-Bias Assessment of Included Studies

Figure 1 PRISMA diagram showing study selection.

NCT02931838 was a 12-week, randomized, placebo-controlled, dose-ranging Phase II clinical trial that included 267 adults with moderate-to-severe plaque psoriasis (sPGA 3, PASI 12, and BSA 10%; mean baseline PASI was 18).24 The primary clinical outcome assessed was PASI 75 at Week 12 compared to baseline. Patients were randomly assigned to one of six groups to receive placebo medication or deucravacitinib orally at the following frequencies: 3 mg every other day (QOD), 3 mg daily (QD), 3 mg twice daily (BID), 6 mg BID, or 12 mg QD. Detailed clinical outcomes can be found in Table 1; improvements in PASI scores were associated with higher doses of deucravacitinib and were improved compared to placebo groups. Nearly 70% of the cohort that received deucravacitinib 3 mg BID (closest to the FDA-approved dosage of 6 mg once daily) achieved PASI 75 at Week 12, compared to 6.7% of the placebo cohort. Improvements in clinical outcomes were correlated with biomarker changes and patient-reported quality-of-life (percent of patients who achieved DLQI 0/1).27

POETYK PSO-1 (NCT03624127) and POETYK PSO-2 (NCT03611751) were randomized, double-blind, double-dummy Phase III trials that compared the efficacy and safety of deucravacitinib versus an active-comparator (apremilast) and placebo.25,26 A total of 666 patients (PSO-1) and 1020 patients (PSO-2) were randomized 2:1:1 to deucravacitinib 6 mg QD, apremilast 30 mg BID, or placebo. All participants receiving placebo were crossed over to receive deucravacitinib at Week 16; patients receiving apremilast who did not achieve PASI 50 (PSO-1) or PASI 75 (PSO-2) by Week 16 were also switched to the deucravacitinib group. In PSO-2, deucravacitinib patients achieving PASI 75 at Week 24 were re-randomized 1:1 to deucravacitinib at the same dosing schedule or placebo for the remainder of the study. If the newly switched placebo patients exhibited disease relapse, they were re-started on deucravacitinib.

Detailed clinical outcomes for both studies are reported in Table 1; briefly, deucravacitinib was shown to be more effective than both comparator and placebo at Week 16 for both primary endpoints assessed (PASI 75 and sPGA 0/1). The percent of patients who achieved PASI 75 in PSO-1 and PSO-2 (vs apremilast, placebo) were 58.7% (vs 35.1%, 12.7%) and 53.6% (vs 40.2%, 9.4%), respectively. The percent of patients who achieved sPGA 0/1 in PSO-1 and PSO-2 (vs apremilast, placebo) were 53.6% (vs 32.1%, 7.2%) and 50.3% (34.3%, 8.6%), respectively.

In all included studies, deucravacitinib was well-tolerated, with similar percentages and types of adverse events (AEs) reported among patients treated with placebo or comparator drugs at Week 12 or 16.2426 The occurrence of any AE by Week 12 or 16 in NCT02931838, POETYK PSO-1, and POETYK PSO-2 were 64% (vs 51% in placebo group), 53.0% (vs 42.4% in placebo group, 55.4% in apremilast group), and 57.5% (vs 54.3% in placebo group, 59.1% in apremilast group), respectively. In all trials, the most frequently reported AEs associated with deucravacitinib were nasopharyngitis (6.311%) and upper respiratory tract infection (26.3%). Other common AEs reported in the POETYK trials included headache (4.34.8% vs 3.05.5% in placebo group vs 10.111.0% in apremilast group), diarrhea (3.94.7% vs 3.67.5% in placebo group vs 10.113.0% in apremilast group), and nausea (1.22.1% vs 1.42.4% in placebo group vs 9.111.3% in apremilast group), which occurred at similar frequencies to placebo and generally decreased frequencies compared to the apremilast treatment group. Across the three studies, no significant changes in mean blood counts (including neutrophil and platelet levels), serum lipids (including total cholesterol), creatinine, creatine phosphokinase, liver enzymes, or immunoglobulins were reported. Among all patients treated with deucravacitinib, no serious cases of herpes zoster leading to discontinuation occurred; additionally, no opportunistic infections or tuberculosis were reported.

Meta-analysis of the three placebo-controlled RCTs comparing the rates of clearance (sPGA 0/1) in patients with moderate-to-severe psoriasis (N = 1354; deucravacitinib, n = 888; placebo, n = 466) demonstrated superior efficacy of deucravacitinib compared to placebo (OR, 12.87; 95% confidence interval (CI), 8.9718.48) (Figure 2). Heterogeneity was determined as significant (2 = 4.08, I2 = 51%) (Figure 2).

Figure 2 Forest plot of deucravacitinib versus placebo in the treatment of moderate-to-severe psoriasis. The primary outcome assessed was achievement of static Physician Global Assessment (sPGA) 0 or 1 at Week 12 (NCT02931838) or Week 16 (POETYK trials) in deucravacitinib- versus placebo-treated patients.

Abbreviations: CI, confidence interval; df, degrees of freedom; M-H, Mantel-Haenszel fixed-effects method.

Psoriasis is a systemic, immune dysregulatory condition that has a significant detrimental impact on a patients overall health and quality of life. While a range of biologic therapies are available for the treatment of more severe diseaseincluding agents that target TNF-, IL-12/IL-23, IL-17, and IL-23certain biologics can be contraindicated for individuals based on comorbid conditions, safety concerns, or insurance coverage issues. Furthermore, patients with more severe psoriasis are more likely to experience biologic failure, including the sequential failure of multiple biologics, despite adequate time attempting each agent.2830 Thus, there remains a need to develop new targeted therapeuticsparticularly those that can act via a different mechanism of action than existing systemic agentsto treat patients with moderate-to-severe psoriasis.

While the development of psoriasis is complex and involves an interplay between multiple immune signaling pathways, JAK/STAT signaling has been shown to hold a central dysregulatory role in psoriasis pathogenesis for years.16 The importance of such signaling in psoriasis was further emphasized after a recent study found methotrexate to inhibit the JAK/STAT pathway as a potential secondary mechanism of action, particularly relevant in psoriatic arthritis.31 Unfortunately, first-generation JAK inhibitors targeting JAK2 and JAK3 (eg, tofacitinib, baricitinib) experienced limited success for psoriasis as a disease indication due to safety concerns, despite effective associated clinical outcomes (eg, PASI reduction).32,33 For example, incidence of major adverse cardiovascular events and cancer were found to be higher in tofacitinib-treated groups in a dose-dependent fashion for rheumatoid arthritis patients.34 Thus, JAK inhibitors were previously approved only for psoriatic arthritis or for off-label use in certain psoriasis patients who had not responded to conventional systemic therapies.33

Deucravacitinib represents a major advancement as a first-in-class systemic therapy that differs from prior JAK inhibitors and other psoriasis biologics in several ways. First, deucravacitinib is a small molecule, meaning it can be administered by a variety of routes, including orallyas opposed to injected or infused, as many psoriasis biologics are.35 Because of deucravacitinibs oral bioavailability and simpler dosing regimens, adherence to the intended treatment plan may be easier to achieve for patients, and access to first-line therapy for moderate-to-severe psoriasis may be expanded due to lower drug costs.35 Additionally, small molecules may also hold a reduced risk of immunogenicity compared to biologics, which can translate to a longer period of efficacy in individual patients.35 Finally, our systematic review of RCTs found that psoriasis patients treated with deucravacitinib did not experience major AEs at rates significantly different from patients treated with apremilast or placebo.26,36 In our review of the three included RCTs, the most frequently reported AEs tended to occur at similar rates compared to the placebo group and at lower frequencies compared to apremilast treatment. None of the three included RCTs reported significant changes in blood count, cholesterol levels, or opportunistic infections among patients treated with deucravacitinib, which were all concerns that hampered the approval of JAK inhibitors for psoriasis treatment in the past.37,38 Taken together, these results suggest that deucravacitinib may have favorable safety features as a selective inhibitor of TYK2 in the JAK familyalthough results should be interpreted with caution due to the limited follow-up periods reported. Further head-to-head comparative studies should be conducted.

The meta-analysis conducted in our study is, to our knowledge, the first performed that compares plaque psoriasis patients treated with deucravacitinib versus placebo. The results (Figure 2) indicate that the primary endpoint of sPGA 0/1, a validated tool providing a global estimate of a patients psoriatic disease severity, was achieved significantly more frequently in deucravacitinib compared to placebo treatment groups.18 These promising results of clinical efficacy bode well for other TYK2 inhibitors in clinical development for psoriasis, including rapsacitinib, brepocitinib, NDI-034858, and ESK-001.33 Overall, our systematic review and meta-analysis found deucravacitinib to yield positive improvements for multiple efficacy endpoints, including clinical outcomes (eg, sPGA, PASI) and patient-reported quality of life (via DLQI).

Deucravacitinib is an effective, oral small molecule that possesses good efficacy and safety features, indicating its potential to serve as a first-line treatment for moderate-to-severe psoriasis. Patients with plaque psoriasis showed significant improvements in objective, disease-specific clinical parameters, with meta-analysis of Phase II and III RCTs demonstrating the superiority of deucravacitinib compared to placebo. Within individual RCTs, deucravacitinib was also found to yield increased rates of disease improvement and reduced AE incidence compared to apremilast. Thus, deucravacitinib achieved clinical efficacy while maintaining a favorable safety profilean important barrier to prior JAK inhibitor use in psoriasisconsistent with its unique mechanism of action and selectivity for TYK2. While further studies should be conducted to evaluate the long-term safety and efficacy of deucravacitinib and compare it to existing biologics, deucravacitinib holds promising clinical utility and represents an important step forward as a first-in-class treatment option for psoriasis patients.

AE, adverse event; BID, twice daily; CASP, Critical Appraisal Skills Programme; DLQI, Dermatology Life Quality Index; FDA, Food and Drug Administration; IL, interleukin; JAK, Janus kinase; PASI, Psoriasis Area and Severity Index; PGA, Physician Global Assessment; PGA-F, PGA of Fingernail Psoriasis; QD, daily; QOD, every other day; RCT, randomized controlled trial; sPGA, static PGA; ss-PGA, scalp-specific PGA; STAT, Signal Transducers and Activators of Transcription; Th17, T helper 17; TYK, tyrosine kinase.

All data analyzed in this systematic review can be searched in publicly available databases including PubMed and Embase.

This is a review article of published studies; ethics approval was not required by our Institutional Review Board.

No identifiable patient information was included in this article.

We are thankful to all the reviewers who contributed to this article.

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this manuscript. All authors contributed to data analysis, drafting or revising the article, have agreed on the journal to which the article will be submitted, gave final approval of the version to be published, and agree to be accountable for all aspects of the work. Conception: JQJ, VR, WL. Methodology: all authors. Formal analysis and investigation: JQJ, RKS. Writingoriginal draft preparation: JQJ, RKS. Writingreview and editing: all authors. Supervision: WL.

This study was not funded.

J.Q.J. has received research grant funding from the National Psoriasis Foundation and institutional funding from the University of California, San Francisco. T.B. has received research grant funding from Novartis and Regeneron and is a principal investigator for trials sponsored by Abbvie, Castle, CorEvitas, Dermavant, Galderma, Mindera, and Pfizer. T.B. has also served as an advisor for Abbvie, Arcutis, Boehringer-Ingelheim, Bristol Myers Squibb, Janssen, Leo, Lilly, Novartis, Pfizer, Sun, and UCB. W.L. has received research grant funding from Abbvie, Amgen, Janssen, Leo, Novartis, Pfizer, Regeneron, and TRex Bio. The authors report no other conflicts of interest in this work.

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17. Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372. doi:10.1136/BMJ.N71

18. Robinson A, Kardos M, Kimball AB. Physician Global Assessment (PGA) and Psoriasis Area and Severity Index (PASI): why do both? A systematic analysis of randomized controlled trials of biologic agents for moderate to severe plaque psoriasis. J Am Acad Dermatol. 2012;66(3):369375. doi:10.1016/J.JAAD.2011.01.022

19. Mattei PL, Corey KC, Kimball AB. Psoriasis Area Severity Index (PASI) and the Dermatology Life Quality Index (DLQI): the correlation between disease severity and psychological burden in patients treated with biological therapies. J Eur Acad Dermatol Venereol. 2014;28(3):333337. doi:10.1111/JDV.12106

20. Catlett IM, Aras U, Hansen L, et al. First-in-human study of deucravacitinib: a selective, potent, allosteric small-molecule inhibitor of tyrosine kinase 2. Clin Transl Sci. 2023;16(1):151164. doi:10.1111/CTS.13435

21. Mease PJ, Deodhar AA, Van Der Heijde D, et al. Efficacy and safety of selective TYK2 inhibitor, deucravacitinib, in a phase II trial in psoriatic arthritis. Ann Rheum Dis. 2022;81(6):815822. doi:10.1136/ANNRHEUMDIS-2021-221664

22. CASP CHECKLISTS - CASP - critical appraisal skills programme. Available from: https://casp-uk.net/casp-tools-checklists/. Accessed September 21, 2022.

23. Cochrane Training. Chapter 10: analysing data and undertaking meta-analyses. Available from: https://training.cochrane.org/handbook/current/chapter-10. Accessed March 15, 2023.

24. Papp K, Gordon K, Thai D, et al. Phase 2 trial of selective tyrosine kinase 2 inhibition in psoriasis. N Engl J Med. 2018;379(14):13131321. doi:10.1056/NEJMOA1806382/SUPPL_FILE/NEJMOA1806382_DATA-SHARING.PDF

25. Armstrong AW, Gooderham M, Warren RB, et al. Deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: efficacy and safety results from the 52-week, randomized, double-blinded, placebo-controlled Phase 3 POETYK PSO-1 trial. J Am Acad Dermatol. 2023;88(1):2939. doi:10.1016/J.JAAD.2022.07.002

26. Strober B, Thai D, Sofen H, et al. Deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: efficacy and safety results from the 52-week, randomized, double-blinded, phase 3 program for evaluation of TYK2 inhibitor psoriasis second trial. J Am Acad Dermatol. 2023;88(1):4051. doi:10.1016/J.JAAD.2022.08.061

27. Thai D, Strober B, Gordon KB, et al. Deucravacitinib in moderate to severe psoriasis: clinical and quality-of-life outcomes in a phase 2 trial. Dermatol Ther (Heidelb). 2022;12(2):495510. doi:10.1007/S13555-021-00649-Y

28. Mastorino L, Roccuzzo G, Dapavo P, et al. Patients with psoriasis resistant to multiple biological therapies: characteristics and definition of a difficult-to-treat population. Br J Dermatol. 2022;187(2):263265. doi:10.1111/BJD.21048

29. Hadeler E, Kumar S, Yeroushalmi S, et al. Factors associated with multi-biologic use in psoriasis patients at an academic medical center and review of biologic survival. J Psoriasis Psoriatic Arthritis. 2022. doi:10.1177/24755303221131259

30. Shalom G, Cohen AD, Ziv M, et al. Biologic drug survival in Israeli psoriasis patients. J Am Acad Dermatol. 2017;76(4):662669.e1. doi:10.1016/J.JAAD.2016.10.033

31. Gremese E, Alivernini S, Tolusso B, Zeidler MP, Ferraccioli G. JAK inhibition by methotrexate (and csDMARDs) may explain clinical efficacy as monotherapy and combination therapy. J Leukoc Biol. 2019;106(5):10631068. doi:10.1002/JLB.5RU0519-145R

32. Jo CE, Gooderham M, Beecker J. TYK 2 inhibitors for the treatment of dermatologic conditions: the evolution of JAK inhibitors. Int J Dermatol. 2022;61(2):139147. doi:10.1111/IJD.15605

33. Loo WJ, Turchin I, Prajapati VH, et al. Clinical implications of targeting the JAK-STAT pathway in psoriatic disease: emphasis on the TYK2 pathway. J Cutan Med Surg. 2022. doi:10.1177/12034754221141680/ASSET/IMAGES/LARGE/10.1177_12034754221141680-FIG2.JPEG

34. Ytterberg SR, Bhatt DL, Mikuls TR, et al. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis. N Engl J Med. 2022;386(4):316326. doi:10.1056/NEJMOA2109927/SUPPL_FILE/NEJMOA2109927_DATA-SHARING.PDF

35. Makurvet FD. Biologics vs. small molecules: drug costs and patient access. Med Drug Discov. 2021;9:100075. doi:10.1016/J.MEDIDD.2020.100075

36. Armstrong AW, Gooderham M, Warren RB, et al. Deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: efficacy and safety results from the 52-week, randomized, double-blinded, placebo-controlled phase 3 POETYK PSO-1 trial. J Am Acad Dermatol. 2022. doi:10.1016/J.JAAD.2022.07.002

37. Canada.ca. Health Canada safety review finds link between the use of Xeljanz and Xeljanz XR (tofacitinib) and increased risk of serious heart-related issues and cancer. Available from: https://recalls-rappels.canada.ca/en/alert-recall/health-canada-safety-review-finds-link-between-use-xeljanz-and-xeljanz-xr-tofacitinib. Accessed March 15, 2023.

38. FDA. FDA requires warnings about increased risk of serious heart-related events, cancer, blood clots, and death for JAK inhibitors that treat certain chronic inflammatory conditions. Available from: https://www.fda.gov/drugs/drug-safety-and-availability/fda-requires-warnings-about-increased-risk-serious-heart-related-events-cancer-blood-clots-and-death. Accessed March 15, 2023.

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Clinical Utility of Deucravacitinib for the Management of Moderate to ... - Dove Medical Press

Psoriasis flares have long been associated with bacterial and viral infections

ISLAMABAD, (ONLINE) - New research is shedding light on how an infection with Covid-19 may reactivate, or even cause, psoriasis. The skin condition affects about 7.5 million adults in the United States, according to the National Psoriasis Foundation. Psoriasis has several well-established triggers, including stress, skin injury, cold or warm air, and allergies. Illnesses like strep throat can also cause a psoriasis flare in some people and it appears Covid may also do so.

Psoriasis flares have long been associated with bacterial and viral infections, particularly a form of psoriasis called guttate, which is characterized by tons of tiny red scaly bumps all over the body, said Joel M. Gelfand, MD, a professor of dermatology and epidemiology at the University of Pennsylvanias Perelman School of Medicine in Philadelphia. Infection with Covid-19 has been associated with flares of guttate and pustular psoriasis, and even psoriasis that affects 100% of the skin, which is called erythroderma, in many published case reports.

What Makes Your Psoriasis Severe?Your immune system is actually to blame for those itchy, sore patches of skin. Its considered severe when it covers what percentage of your body?

A study from Albany Medical College/Weirton Medical Center found that people in the study who were already diagnosed with the skin condition had an unexpected flare within a week to a month after testing positive for Covid. New psoriasis after a Covid infection was also found. The researchers think this could be because Covid causes inflammation in the body, which negatively affects previously well-controlled psoriasis. They also think its possible that Covid-related inflammation could trigger a genetic tendency to have psoriasis, which may explain why it can appear for the first time after a positive test.

Inflammation in the body commonly manifests itself through skin conditions.

The skin is the largest organ in the body, said Robert O. Carpenter, MD, director of wellness at Texas A&M College of Medicine in Bryan, TX. A viral infection like Covid-19 can signal the release of pro-inflammatory factors that can appear as rashes, such as with psoriasis.What are the Symptoms of Covid-Related Psoriasis?

The signs are the same as those of any form of psoriasis. According to the Mayo Clinic, these signs can include:

A patchy, scaly, raised red rash. Psoriasis can also be purple, pink, gray, brown or silver. The rash can appear anywhere on the body. Psoriasis can also look like dandruff.

Dry, cracking skin that sometimes peels

Itching, burning, or painful skin

If I Have Psoriasis, Will COVID Automatically Make It Worse?

Not necessarily.

Psoriasis is a common condition, so people should be aware that new psoriasis that develops may not be related to Covid-19, said Esther Freeman MD, PhD, director of global health dermatology at Massachusetts General Hospital in Boston.

As with every aspect of Covid, doctors and scientists are still learning about how serious and widespread a problem psoriasis after Covid-19 may be. We have seen case reports that psoriasis can flare after Covid-19, said Freeman, who is also an associate professor of dermatology at Harvard Medical School. I will say, this has not been a tidal wave more like sporadic cases here and there. So I do not think psoriasis flares are a major post-Covid finding, nor do they necessarily mean you have long Covid. That being said, we know that many different infections can cause psoriasis flares, and so in that respect, it's not that surprising that SARS-CoV-2, like other infections, could trigger a psoriasis flare.

Could getting Covid more than once cause psoriasis to flare? Its possible.

Your body can change after having Covid-19, said Carpenter. We dont know the long-term implications, but having Covid-19 repeatedly can increase the risk of long Covid, which can cause many systemic changes in your body."

Another important point: If you take biologics, the immune-modulating therapy to treat psoriasis, getting vaccinated and boosted for Covid is an important step to take to help protect yourself.

Is Psoriasis Itself a Potential Symptom of Covid?

Yes, but we dont know the frequency at which this may occur, and a causal relationship is difficult to establish from just case reports, said Gelfand, whos also medical director of the Clinical Studies Unit in the Department of Dermatology at his university. Typically, if a patient presents with a flare of psoriasis, particularly guttate, pustular, or erythrodermic forms, an infectious trigger should be considered, and testing for strep and possibly Covid-19 may be appropriate.

If you do have a flare of psoriasis, or get one for the first time after testing positive for Covid, you should also ask your dermatologist about new treatment options.

Original post:
Covid-19 and Psoriasis: Is there a link? - Dunya News

A new systematic review has identified common strategies for and gaps in ensuring adherence to self-monitoring for early detection of new or recurrent melanoma, a complex challenge affected by various interacting factors.

The study, using an adaption of the World Health Organization (WHO) framework for adherence, characterized strategies built into the design, conduct, and reporting of melanoma trials, offering insights into potential improvements for these strategies in research. Currently, few high-risk patients routinely perform skin self-examination (SSE) frequently or thoroughly.

There is currently limited practical guidance for the best practices to maximize adherence to SSE in research or practice, wrote the researchers in JAMA Dermatology. Assessment of adherence to an intervention in a trial may provide valuable insights on the ease with which it can be translated into routine clinical practice. Trialists may consider developing a comprehensive adherence plan as part of the study protocol, including strategies for dealing with nonadherence, and may find our adaptation of the WHO adherence framework helpful for this. However, care is needed to ensure strategies are achievable in everyday routine care.

The 18 randomized controlled trials included in the analysis ranged from 40 to over 700 patients. Various approaches to bolster adherence to SSE were leveraged in the trials, including trial design, social support, intervention design, intervention and condition support, and participant support.

Intervention design was used by all trials to increase adherence, 13 of which used theories of health behavior change, 2 of which reported on patient and public involvement in the study design and materials, and 1 of which reported codesign of the intervention with potential recipients.

The most common trial design strategy was eligibility criteria limits, used by 14 of the studies. These criteria typically limited eligibility to patients who spoke English and who were more likely to adhere to self-monitoring practices, assessed with pretests for adherence.

Social support was offered in 5 trials, all of which provided access to health care professionals and services. In some trials, research staff helped with urgent clinical appointments, while in others, information was provided on how to access care and calendar scheduling was enabled for scheduling doctor appointments. Some of these trials offered information on melanoma risk within families through an internet-based education tool.

The researchers noted that no trials used economic support to cover additional costs nor ensured materials were sensitive to health literacy. As a result, they wrote, diversity in the trials may have unintentionally been hindered, leading to underrepresentation of certain groups of patients.

Research is needed to identify adherence interventions that are low cost and can be easily integrated into the workflow of routine clinical practice, including automated digital interventions, explained the researchers. Interventions that require the active participation of health care professionals or large administrative support may be difficult to implement in busy clinical contexts. Evaluation of individual components of a complex intervention may be undertaken using a SWAT [Studies Within A Trial] repository within the host randomized clinical trial: a self-contained study that has been embedded within a host trial with the aim of evaluating or exploring alternative ways of delivering or organizing a particular trial process.

The researchers noted that SWAT may have direct effects on adherence in the host trial while offering generalizable results for other trials and guiding implementation post trial.

Reference

Ackermann D, Bracken K, Janda M, et al. Strategies to improve adherence to skin self-examination and other self-management practices in people at high risk of melanoma: a scoping review of randomized controlled trials. JAMA Dermatol. 2023;159(4):432-440. doi:10.1001/jamadermatol.2022.6478

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Improvement Needed in Study Interventions to Better Skin Self ... - AJMC.com Managed Markets Network

Brilaroxazine topical liposomal-gel formulation (brilaroxazine lipogel) demonstrated proof-of-concept efficacy in the imiquimod-induced psoriatic mouse model

IND submission for brilaroxazine lipogel in psoriasis expected in 2024

Reviva has filed composition of matter patent for brilaroxazine-lipogel and a separate patent for use in the treatment of psoriasis

Preclinical efficacy data presented at the ISID 2023 meeting

CUPERTINO, Calif., May 11, 2023 (GLOBE NEWSWIRE) -- Reviva Pharmaceuticals Holdings, Inc. (NASDAQ: RVPH) (Reviva or the Company), a clinical-stage pharmaceutical company developing therapies that seek to address unmet medical needs in the areas of central nervous system (CNS), respiratory and metabolic diseases, has presented promising preclinical data on the potential of novel serotonin-dopamine stabilizer brilaroxazine for the treatment of psoriasis at the First International Societies for Investigative Dermatology (ISID) Meeting in Tokyo, Japan, May 10-13, 2023. The ISID poster is available at revivapharma.com/publications.

The multifaceted activity of brilaroxazine offers the promise to improve the quality of life and provide a novel treatment option for patients with psoriasis, an inflammatory condition stemming from serotonin and dopamine dysfunction, said Laxminarayan Bhat, Ph.D., Founder, President, and CEO of Reviva. We were excited to present encouraging preclinical data at ISID 2023 highlighting the therapeutic potential of brilaroxazine lipogel, a novel, proprietary lipogel formulation for the topical treatment of psoriasis. We have filed a composition of matter patent for brilaroxazine-lipogel and a separate patent for its use in psoriasis. Mental illness, including schizophrenia and depression, is a major comorbidity in patients with psoriasis. Brilaroxazine has established a well-tolerated safety profile with robust efficacy in about 300 patients with schizophrenia from Phase 1B and Phase 2 studies. To further explore this therapeutic potential, we intend to submit an investigational new drug application (IND) for brilaroxazine lipogel in psoriasis in 2024.

Psoriasis is a chronic dermal inflammatory disease with a global prevalence of ~125 million. Dopamine (D) and serotonin (5-HT) signaling pathways play an important role in the pathobiology of psoriasis, and lead to increased inflammatory mediators (TNF-, IFN-, IL-1, IL-6, IL-8), keratinocyte activation and deterioration, and worsening symptoms. Current treatments include multiple modalities but are limited by long-term side effects (topicals), toxicities (orals) or risk of immunogenicity, serious infection, and malignancy (biologics). Brilaroxazine (RP5063) is a modulator of D and 5-HT receptors with multifaceted activity that may affect underlying psoriasis pathology. Preclinical studies in the imiquimod-induced psoriatic mouse model (BALB/c) were used to evaluate the potential of topical liposomal-gel formulation of brilaroxazine for the treatment of psoriasis.

Key poster highlights support the therapeutic potential of brilaroxazine lipogel in psoriasis:

2023 GlobeNewswire, Inc., source Press Releases

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Reviva Pharmaceuticals Announces Intent to File an IND for Brilaroxazine in Psoriasis After Promising Preclinical Data - Marketscreener.com

During this HCPLive interview, Adam Friedman, MD, spoke on concerns about disparities between different groups with atopic dermatitis and the ways in which he hopes to address them.

Friedmans discussion was the result of his presentation from the Revolutionizing Atopic Dermatitis (RAD) 2023 Annual Meeting in Washington, DC., during which he presented on Using teledermatology to reduce disparities in atopic dermatitis care.

He is known for his work as Professor and Chair of Dermatology in the Department of Dermatology at the George Washington University School of Medicine & Health Sciences.

I think there's certainly more global disparities, he explained. And there are a lot of different reasons for them. I think that they range from when we say access, that can mean a lot of things. It can mean having a physician or a specialist in your area that you can physically access or even if you do, can you even get into see that person because they're so overwhelmed with patients, does it mean that you can physically get there, (or) whether you have the means to get to a visit?

He added that there are disparities between different populations, noting that there are many different subgroups and variables.

But we do see with atopic dermatitis, for example, those who identify as black depending on certain studies or African Americanoften those terms are put side by side and they're not the same, but that's what we seethat there is a higher prevalence of disease, more severe disease, he said. But those individuals make up a very small subset of those who are actually being seen by dermatologists.

Friedman added that dermatologists know that socioeconomic status is an independent risk factor for more severe and uncontrolled diseases.

So I think there's a lot more to learn and I think the way we solicit information will ultimately lend itself to better understanding the needs of specific communities and populations, he explained. But certainly from the information we have, there are those who seem to be at higher risk for all the horrific primary and secondary things that atopic dermatitis can cause and lead to down the road.

For more information about Friedmans presentation, view the full interview segment above.

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Adam Friedman, MD: Addressing Disparities in Care for Patients ... - MD Magazine

Epilepsy should be added to the list of neurological outcomes following an infection of invasive Group BStreptococcus(iGBS)particularly meningitisin early infancy, new study results suggest.

Findings from a population-based cohort study, published in JAMA Network Open, revealed iGBS disease was linked with a higher incidence of epilepsy in later childhood, notably after meningitis. The risk of epilepsy in later childhood was higher among those born prematurely, males, or those born to a mother belonging to a low socioeconomic position (SEP).

iGBS disease is a leading cause of neonatal and young infant mortality around the world. In 2020, it was estimated that 500,000 cases of iGBS disease occurred within the first 3 months after birth, the authors wrote.

Although epilepsy has been reported as an outcome following iGBS disease, particularly meningitis, the risk of the condition after neonatal iGBS disease has yet to be investigated further, the researchers said. To address this knowledge gap, they studied children with iGBS born in Denmark between 1997 and 2017. Follow-up continued until the end of 2018.

A total of 1432 children with iGBS disease (sepsis, n = 1264; meningitis, n = 168) were included in the study and compared with 14,211 unaffected children. All participants were aged between 0 and 89 days, 55.3% were male, and nearly 79% had a gestational age of at least 37 weeks. The mothers SEP was determined via income and education level.

Analyses revealed:

Overall, we found a significantly higher risk of epilepsy in children with iGBS meningitis in later childhood compared with children not exposed to iGBS, the authors wrote. The risk of epilepsy for iGBS sepsis was not significant.

Compared with those without iGBS, the cumulative incidence of epilepsy was higher within the first 5 years after diagnosis of iGBS.

To the authors knowledge, the study is the first to examine the long-term risk of epilepsy as an individual outcome after iGBS sepsis or meningitis.

The large cohort of children with iGBS disease and comparison group, in addition to long-term follow-up until adolescence, mark strengths of the current investigation. Researchers were also able to match groups on all matching variables with small differences between cohorts, helping to reduce residual confounding.

However, data for iGBS onset were defined based on admission date, meaning the study may have excluded iGBS infections from the day of birth. Results should also be interpreted with caution, due to the small size of the iGBS meningitis cohort, the authors noted. Data also did not account for childhood accidents, infectious diseases, or head trauma that took place after the index date.

Our findings have implications for estimating the global burden of iGBS and should be considered in relation to the cost-effectiveness of interventions, such as intrapartum antibiotic prophylaxis and maternal vaccination, the authors concluded. Importantly, these data also have implications for affected individuals and underline the need for better long-term follow-up and care.

Reference

Lykke MR, Srensen HT, Lawn JE, Horvth-Puh E. Long-term risk of epilepsy following invasive group B Streptococcusdisease in neonates in Denmark. JAMA Netw Open. Published online April 21, 2023. doi:10.1001/jamanetworkopen.2023.9507

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Early-Infancy Meningitis Infection Linked With Increased Risk of ... - AJMC.com Managed Markets Network

By John Vandermosten, CFA

NASDAQ:NOVN

READ THE FULL NOVN RESEARCH REPORT

1Q:23 Financial and Operational Results

On May 15th, 2023, Novan Inc. (NASDAQ:NOVN) reported 1Q:23 financial and operational results in a press release and in the filing of Form 10-Q. A conference call and webcast were subsequently held to update investors on recent developments. The call highlighted the performance of the EPI Health assets and efforts related to SB206s New Drug Application (NDA) which has been assigned a target action date of January 25th, 2024. Novan is increasingly focused on potential funding or strategic arrangements and alternatives to address short-term cash needs and access to capital is necessary to progress development of SB206. Since the report of 2022 results in late March, Novan held an analyst and investor day and announced a publication supportive of patient use of Wynzora.

Highlights for 2023 include:

SB206 NDA submitted for molluscum contagiosum January 2023

NDA accepted for SB206 assigning 5JAN24 PDUFA date March 2023

$6 million registered direct offering March 2023

Investor KOL event with Dr. Sugarman on molluscum unmet need April 2023

Publication of survey on patient needs for psoriasis medication April 2023

With respect to financial performance, Novan generated $3.2 million in 1Q:23 revenues versus $1.9 million in 1Q:22, and posted a net loss of ($14.1) million or ($0.54) per share compared to a loss of ($13.4) million or ($0.71) per share in the prior year period.

For the quarter ending March 31, 2023 and versus the same prior year period:

Revenues were $3.2 million, up 64% from $1.9 million. The increase is predominantly due to revenue contribution from sales of dermatology products Wynzora, Rhofade, Minolira and Cloderm and recognition of a full quarter of sales in 1Q:23 compared with 20 days of sales in 1Q:22. Year over year increases were tempered by Rhofade suffering a manufacturing delay which led to a to lack of inventory and loss of sales in 1Q:23; however, management noted that a rebound in orders was experienced in the second quarter as units were restocked. Furthermore, deductible resets for 2023 contributed to the sequential slowdown in scripts and revenues for Novans three leading products.

Story continues

License and collaboration revenues of $585,000 were down 50% due to the absence of revenues from the distribution and supply agreement for Cloderm. Research and grant revenues were up 370% to $170,000 from $36,000 on recognition of multiple federal grants;

Cost of goods sold was $1.3 million vs. $0.2 million;

Research & development expenses totaled $4.8 million, essentially flat with prior year levels. Declines in spending on the SB206 program were offset by increases in other research and development expenses related to a $1 million milestone payment to Ligand;

Selling, general & administrative expenses were $10.0 million, also flat with prior year amounts. 1Q:22 expenses related to the EPI acquisition were replaced by greater commercialization spending for the product portfolio in 1Q:23;

Net loss was ($14.1) million, or ($0.54) per basic and diluted share, compared to ($13.4) million, or ($0.71) per share.

As of March 31, 2023, cash and equivalents on the balance sheet totaled $12.5 million. This compares to cash holdings of $12.3 million at the end of 2022. Cash burn was ($4.3) million which was partially offset by $4.1 million of net contributions from financing. $6.0 million of this amount was from the direct offering which was executed in mid-March. $5.0 million was also received from Sato related to the license agreement for Rhofade. $1.25 million of the Sato/Rhofade upfront is owed to a third party tempering the impact from this cash flow. Novan anticipates that there is sufficient liquidity to support operations until late second quarter 2023.

Corporate Updates

Psoriasis Publication

Findings from a National Psoriasis Foundation study were published in the Journal of Drugs in Dermatology which surveyed more than 400 US patients on patient adherence to topical psoriasis medications. The title of the April 2023 publication is Patient Preferences in Topical Psoriasis Treatment by Curcio, et al.1 The 17-question survey was administered in March 2022 and queried participants on psoriasis severity, bothersome signs and symptoms, current treatment modalities, frequency of topical therapy use, and vehicle preferences.

84% of the participants reported moderate psoriasis with 72.5% of participants using oral medication and 8% topical treatment alone. 76% used topical therapy at least once weekly and 80% reported that they would wait two weeks after starting a new topical treatment before considering discontinuation. Participants preferred water-based creams (75.7%), followed by oil-based foam (70.8%), gel (48.7%), solution (42.8%), lotion (21.2%), non-oil-based foam (17.5%), ointment (16.5%), and spray (6.3%). Other desirable features were formulas that did not stain, were absorbed quickly, were not sticky and were easy to apply. 75% said they would continue to use a psoriasis medication for a week before stopping if they didnt like its topical formulation.

Novans press release continued with a summary of Wynzoras features. Novans product, which is commercialized jointly with MC2 Therapeutics, offers a rapid onset of action with results seen in efficacy, scale and itch as early as one week after application and continued improvement at 8 weeks. Additional detail on Wynzoras profile are included in an analysis by Han, et al.2 and in the products label.

A Discussion of Molluscums Unmet Need

Novan held a stakeholder event on April 25th, 2023 featuring pediatric dermatologist Jeffrey Sugarman, MD, PhD to discuss molluscums unmet need with investors and analysts. The presentation began with an introduction by CEO Paula Brown Stafford who summarized the companys pipeline and the status of lead candidate SB-206, which is now being considered for approval by the FDA. She was followed by Chief Commercial Officer Brian Johnson who quantified the unmet need for molluscum patients. Existing options for patients include potentially painful in-office procedures and non-approved approaches that have limited efficacy. Health care providers (HCPs) want to see solutions for MC and are willing to prescribe an effective medicine if available.

To provide the HCP perspective, pediatric dermatologist Dr. Jeffrey Sugarman was featured who also served as the safety monitor for the Phase III clinical trials for SB-206. MC is commonly seen in children from 3 to 8 years of age, but does move outside of this range. Children with MC frequently also experience eczema, which can make the disease uncomfortable in addition to unsightly and contagious. Dr. Sugarman identified some of the features that physicians would like to see in an MC treatment. These include a safe, effective and well-tolerated product that is convenient to use. SB-206 achieves these objectives for patients, including convenience as it is a prescribed product that can be used at home.

Further discussion detailed the manufacturing and commercialization activities that have been taking place and that will take place over the next quarters. Pediatric dermatologists and primary care pediatricians will be the target audience for the anticipated marketing effort. The panel participants brought up the pending target action date for Verricas cantharidin treatment for MC which is in late July. Having two companies commercializing simultaneously could be beneficial for educating providers on the available options.

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DISCLOSURE: Zacks SCR has received compensation from the issuer directly, from an investment manager, or from an investor relations consulting firm, engaged by the issuer, for providing research coverage for a period of no less than one year. Research articles, as seen here, are part of the service Zacks SCR provides and Zacks SCR receives quarterly payments totaling a maximum fee of up to $40,000 annually for these services provided to or regarding the issuer. Full Disclaimer HERE.

________________________

1. Curcio, A., et al. Patient Preferences in Topical Psoriasis Treatment. Journal of Drugs in Dermatology, April 2023.

2. Han, G., Feldman, S., Bhatia, N., & Prstegaard, M. (2022). Dipropionate (Bdp) Cream (Cal 0.005%/Bdp 0.064% W/W) Improves Plaque Psoriasis At Week One In A Phase 3 Trial. SKIN The Journal of Cutaneous Medicine, 6(4), s42. https://doi.org/10.25251/skin.6.supp.42

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NOVN: Counting Down to PDUFA - Yahoo Finance

In 2022, the global Psoriatic Arthritis (PsA) Treatment Market sales is expected to exceed US$ 10.3 billion. The market is expected to reach US$ 15.6 billion by 2028, growing at a strong 7.1% CAGR.

According to Future Market Insights, the Psoriatic Arthritis (PsA) Treatment Market would grow at a 7.1% CAGR between 2022 and 2028, up from a 6.7% CAGR between 2013 and 2021.

According to the Arthritis Foundation, nearly 70% of psoriasis patients are predisposed to psoriatic arthritis, and up to 20% of arthritis patients are predisposed to psoriasis.

For more insights into the market, request a sample of this report@ https://www.futuremarketinsights.com/reports/sample/rep-gb-2718

In recent years, the increasing burden of psoriasis and psoriatic arthritis on the healthcare industry has boosted clinical research in the field of psoriatic arthritis.

Sustained adoption of conventional disease modifying anti-rheumatic drugs (DMARDs), especially in cost sensitive regions, is projected to push the demand forpsoriatic arthritis treatmentin coming years.

Role of Strong Product Pipeline & Mounting Clinical Research Investments

According to the National Psoriasis Foundation, around 20 medicines for psoriasis and psoriatic arthritis are now in phase II clinical trials, with another 28 in phase III. However, around 24 medicines have already been approved by the FDA for use in the treatment of psoriasis and psoriatic arthritis.

While a solid product pipeline continues to boost demand for psoriasis and psoriatic arthritis treatment, recent data indicates that numerous drug manufacturers are moving their focus to competitive pricing methods in an effort to achieve general adoption in the future years. Future Market Insights recently published new insight based on its analysis of the worldwide psoriatic arthritis therapy market. According to the analysis, the market would grow at a rate of more than 7% per year by 2022.

Industry Behemoths Cover More than 55% Market Value Share

In a largely consolidated worldwide landscape of psoriatic arthritis treatment market, industry giants such as Novartis AG and AbbVie Inc., which include biologics in their core portfolio, account for more than 55% of total revenue. While market leaders continue to focus on FDA clearances and clinical trials, data indicates that different pricing strategies are becoming increasingly important.

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Moreover, prominent players in psoriatic arthritis treatment market are likely to augment investments in R&D of biosimilars, biologics, and TNF (tumor necrosis factor) inhibitors to target regional markets. A number of leading drug manufacturers are also maintaining sizable investments in DMARDs that are scheduled for market entry in next few years. This is perceived as a strong factor improving growth prospects of psoriatic arthritis treatment market, according to the report.

Besides all these, strategic acquisitions, partnerships, and collaborations will remain the preferred expansion strategies adopted by a majority of prominent operators in psoriatic arthritis treatment landscape, says a senior research analyst at the company.

Demand for Biologics & DMARDs Gaining Momentum

Research-driven understanding of the pathophysiology of psoriatic arthritis is fueling the introduction of innovative therapies in psoriatic arthritis treatment market, triggering innovations among the market participants thereby supporting the growth of psoriatic arthritis treatment market. Targeted biological therapy has been demonstrating a decent success rate in terms of inducing temporary pain relief resultant of psoriatic arthritis, and thus continues to represent an attractive position in the psoriatic arthritis treatment market.

The report says that the demand for biologics accounts for more than 55% share of the global market revenue, whereas DMARDs demand makes up for more than 3/4thof the total market value. Although a majority of psoriatic arthritis patients opt for injectable as a preferred route of administration of psoriatic arthritis treatment, increasing introduction of innovative oral drugs is uplifting the popularity of orally administered psoriatic arthritis treatment.

Development of novel oral treatments for psoriatic arthritis is likely to favor the growth of North Americas market. Growing availability of combination therapies and relatively economical biosimilar antibody therapeutics are identified to be the primary boosters for the growth of Europes market. Collectively, North America and Europe account for over 60% share in the global value of psoriatic arthritis treatment market. The report indicates that the psoriatic arthritis market in Asia Pacific is likely to display high growth potential in the course of next few years.

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Psoriatic Arthritis (PsA) Treatment Market by Category

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Future Market Insights, Inc. (ESOMAR certified, Stevie Award recipient market research organization and a member of Greater New York Chamber of Commerce) provides in-depth insights into governing factors elevating the demand in the market. It discloses opportunities that will favor the market growth in various segments on the basis of Source, Application, Sales Channel and End Use over the next 10-years.

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Psoriatic Arthritis (PsA) Treatment Market is likely to register CAGR ... - Future Market Insights