Safety and effectiveness of apremilast in Japanese patients with psoriatic disease: Results of a post-marketing surveillance study.

The safety and efficacy of apremilast in psoriatic disease has been demonstrated in clinical trials, including in Japanese patients. This post-marketing surveillance study was conducted after approval of apremalast in Japan in 2016 to evaluate the safety and effectiveness of the drug in Japanese patients with plaque psoriasis (PsO) and psoriatic arthritis (PsA) in routine clinical practice. Patients (enrolled between September 1, 2017, and August 31, 2019), were observed for 12 months after apremilast treatment initiation or until discontinuation or withdrawal. Safety was assessed by evaluating adverse reactions (ARs) and serious ARs. Effectiveness measures in PsO included the proportion of patients who achieved global improvement and Physician's Global Assessment (PGA) scores of 0/1 and the change from baseline in the Dermatology Life Quality Index (DLQI) after 6 and 12 months treatment. The safety analysis set included 1063 patients (PsO, n = 992; PsA, n = 127). ARs and serious ARs were reported in 29.4% and 0.7% of patients, respectively; most occurred <1 month after apremilast initiation. There were no reports of fatal ARs, serious infections, hypersensitivity, or vasculitis. No new safety signals were identified. Among the key survey items, gastrointestinal disorders were the most common ARs (21.3%). In patients with PsO, after 6 and 12 months of treatment, effectiveness rates of achieving highly effective or effective global improvement of were 90.9% and 93.8%; PGA 0/1 was achieved by 42.7% and 58.1% of patients; mean decrease from baseline in total DLQI score was 4.2 (p < 0.0001) and 5.7 (p < 0.0001), respectively. Effectiveness was evaluated in a small number of patients with PsA for some measures; after 6 and 12 months of treatment, improvements were observed in global improvement effectiveness rates, Disease Activity Score in 28 Joints score, Visual Analog Scale score, and DLQI score. We conclude that orally administered apremilast was well tolerated and effective in Japanese patients with PsO and/or PsA enrolled in this post-marketing surveillance study.

Dose escalation of biologic treatment in patients with moderate-to-severe psoriasis in Japan.

Patients receiving interleukin (IL)-inhibiting biologics for moderate-to-severe psoriasis (PsO) may be treated with escalated doses to optimize outcomes. This study evaluated escalation prevalence in a Japanese claims analysis of patients with PsO diagnosis preceding IL-inhibiting biologic treatment and ≥1 post-induction maintenance claim (index date) with sufficient data availability from January 2014 to May 2022. Patients with non-persistence were excluded. Expected daily dose (EDD) was calculated as the recommended maintenance dose divided by the treatment interval. Dose escalation was defined as ≥2 claims showing a ≥20% increase in the observed average daily dose (ADD) over the EDD (with sensitivities requiring ≥1 claim and ≥30%). Significant differences were tested using multivariable regressions. The study included 982 unique patients treated with brodalumab (BRO; n = 104), guselkumab (GUS; n = 207), ixekizumab (IXE; n = 159), risankizumab (RIS; n = 135), secukinumab (SEC; n = 215) and ustekinumab (UST; n = 196). Within 12 months, dose escalation was observed for all IL-inhibiting biologics other than GUS and RIS: 44.4% for UST, 37.2% for IXE, 3.4% for SEC and 1.4% for BRO. In multivariable-adjusted analyses, odds of dose escalation were significantly lower for all products relative to UST. In sensitivities, escalation was observed for all products except RIS.

Systemic therapy for psoriasis and the risk of cutaneous infections.

Systemic treatments are important for patients with moderate-to-severe psoriasis; however, they may occasionally cause adverse infectious events. Although the risk of severe infections with psoriatic treatments is well established, little is known about cutaneous infections. Therefore, we studied the frequency of cutaneous infections in patients with psoriasis who underwent biologic treatment. A total of 878 patients (237 females and 641 males) were analyzed in this follow-up survey conducted in 2020 and based on the Western Japan Psoriasis Registry. The observed skin phenotypes were psoriasis vulgaris (83.3%), pustular psoriasis (7.5%), and psoriatic arthritis (28.9%). The most frequently prescribed systemic drug was apremilast (11.3%), followed by ixekizumab (11.0%), risankizumab (10.9%), and secukinumab (10.4%). The incidence of cutaneous bacterial infections was 12 (1.37% of the total patients), with cellulitis being the most common (8/12, 67%). The incidence of viral infections was 11 (1.25%) including the most common, herpes zoster (9/11, 82%); and that of fungal infections was 45 (5.13%) including 33 (73%) and seven (16%) patients with trichophytosis and oral candidiasis, respectively. Multivariate analysis revealed that cutaneous bacterial infections were frequently observed in patients receiving tumor necrosis factor-α (odds raio [OR] 9.917, 95% confidence interval [CI] 2.069-47.572, p = 0.004) and interleukin (IL)-17 (OR 10.798, 95% CI 2.35-49.616, p = 0.002) inhibitor treatments. A history of otitis media and treatment with oral medications (OR 4.50, 95% CI 1.281-15.804, p = 0.019 and OR 3.80, 95% CI 1.141-12.679, p = 0.03 respectively) were associated with a higher ORs for cutaneous viral infections. Furthermore, age and use of IL-17 inhibitors were associated with elevated ORs for fungal infections. In conclusion, our study reveals that systemic therapies may increase the risk of cutaneous viral infections. Therefore, dermatologists should exercise caution in this regard.

A case of bullous pemphigoid following administration of anti-IL-31 receptor A antibody.

Bullous pemphigoid (BP), an autoimmune bullous dermatosis, occurs predominantly in older individuals. Nemolizumab, a humanized monoclonal antibody against the interleukin (IL)-31 receptor A, is used to treat severe atopic dermatitis (AD) in Japan. However, it can cause several adverse events, such as exacerbation of AD, erythema, and eosinophilia. Herein, we describe a case of prurigo-type AD developing BP after nemolizumab administration. A 62-year-old man with prurigo-type AD and asthma presented with serious, refractory itching. After nemolizumab injection, his pruritus was relieved for 2 days. However, on day 3, erythema with blisters and erosions suddenly appeared throughout his body. Pathological examination showed typical BP and the patient's serum anti-BP180-NC16a antibody level was 882.5 U/mL. Oral prednisolone (PSL) was initiated and nemolizumab was never used again. Despite high-dose PSL, new blisters continued to develop, with a rapid elevation of anti-BP180-NC16a antibodies to 6930 U/mL. Adding high-dose cyclosporine and intravenous gamma globulin reduced new blister formation after 9 weeks, and PSL and cyclosporine were gradually tapered. Dupilumab, an anti-IL-4 receptor antibody, was initiated after 16 weeks, resulting in continued remission without PSL and cyclosporine. The sudden occurrence of BP in this case suggested that the patient had occult BP before the nemolizumab initiation and that nemolizumab exacerbated BP and made it overt. Blocking the IL-31 pathway may exacerbate inflammation in AD or BP, resulting in the acceleration of blister formation. This may be countered by blocking the IL-4/13 pathway with dupilumab. To our knowledge, this is the first case of nemolizumab-exacerbated BP.

Deucravacitinib in plaque psoriasis: 2-year safety and efficacy results from the phase III POETYK trials.

BACKGROUND: In the phase III POETYK PSO-1 and PSO-2 trials, deucravacitinib, an oral selective allosteric tyrosine kinase 2 inhibitor, was well tolerated and efficacious over 1 year in patients with psoriasis. OBJECTIVE: To evaluate deucravacitinib safety and efficacy over 2 years in patients participating in the phase III trials. METHODS: In the POETYK long-term extension (LTE), an ongoing phase IIIb open-label trial, adults with moderate-to-severe plaque psoriasis who completed PSO-1 or PSO-2 receive deucravacitinib 6 mg once daily. Safety was assessed via adverse events (AEs) and laboratory parameter abnormalities. Efficacy endpoints, including ≥ 75% reduction from baseline Psoriasis Area and Severity Index score (PASI 75) and static Physician's Global Assessment (sPGA) score of 0/1 (clear/almost clear), were evaluated in patients originally randomized to deucravacitinib, patients who crossed over from placebo at week 16 and patients who achieved PASI 75 at week 24 (peak efficacy). RESULTS: At data cutoff (1 October 2021), 1519 patients had received at least one dose of deucravacitinib; 79.0% and 39.9% had ≥ 52 weeks and ≥ 104 weeks of total deucravacitinib exposure, respectively. Exposure-adjusted incidence rates (EAIRs) per 100 person-years were similar at 1 year and 2 years for any AEs (229.2 vs. 154.4, respectively), serious AEs (5.7 vs. 6.1), discontinuations (4.4 vs. 2.8), deaths (0.2 vs. 0.4), serious infections (1.7 vs. 2.6), herpes zoster (0.9 vs. 0.8), major adverse cardiovascular events (0.3 vs. 0.4), venous thromboembolic events (0.2 vs. 0.1) and malignancies (1.0 vs. 0.9). EAIRs for COVID-19 infections were higher at 2 years than at 1 year (5.1 vs. 0.5) owing to the peak of the global COVID-19 pandemic occurring during the LTE. No clinically meaningful changes from baseline or trends were observed over 2 years in haematological, chemistry or lipid parameters. Clinical responses were maintained in patients who received continuous deu-cravacitinib treatment from baseline [PASI 75: week 52, 72.4%; week 112, 79.7%; sPGA 0/1: week 52, 57.9%; week 112, 61.1% (as observed)]. Responses at week 52 were also maintained in placebo crossovers and in week-24 PASI-75 responders. CONCLUSIONS: Deucravacitinib maintained efficacy and demonstrated consistent safety with no new safety signals observed through 2 years.

Psoriasis is a chronic inflammatory skin condition. Many available treatments for psoriasis are injected, but can be inadequate in terms of effectiveness, and/or cause serious side-effects. Deucravacitinib is a recently approved oral medicine that interferes with an enzyme involved in inflammation called 'tyrosine kinase 2' (TYK2). Deucravacitinib has been shown to improve psoriatic patches and symptoms (such as itching) through 1 year in two global clinical trials in adults with moderate-to-severe plaque psoriasis (POETYK PSO-1 and PSO-2). This study was an analysis of the safety and efficacy of deu­cravacitinib for up to 2 years. To do this, the researchers used data from approximately 1500 people who completed both trials and continued into an ongoing, long-term extension trial (POETYK LTE). Overall, there were no new side-effects, and the number, type and severity of side-effects, as well as the number of patients who stopped treatment because of these side-effects, remained low. The most frequent side-effects included common cold symptoms and COVID-19. Rates of shingles and serious side-effects were comparable to rates reported in the real world. Improvements in psoriasis symptoms seen at 1 year were maintained for up to 2 years in patients receiving deucravacitinib treatment from the start of PSO-1 or PSO-2, or who crossed over from placebo to deucravacitinib at 4 months. Long-term treatment with deucravacitinib improved psoriasis symptoms and resulted in mostly mild side-effects. The study findings suggest that deucravacitinib could be a well-tolerated and effective treatment for people with psoriasis.

Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, in Japanese patients with moderate to severe plaque, erythrodermic, or generalized pustular psoriasis: Efficacy and safety results from an open-label, phase 3 trial.

Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved in Japan for adult patients with plaque (PP), generalized pustular (GPP), and erythrodermic (EP) psoriasis who have had an inadequate response to conventional systemic therapies. This approval is based on results from the global phase 3 POETYK PSO-1 and PSO-2 trials in which deucravacitinib was associated with significantly improved efficacy outcomes compared with placebo in adults with moderate to severe plaque psoriasis, and results described here from POETYK PSO-4, an open-label, single-arm, phase 3 trial (NCT03924427), which evaluated the efficacy and safety of deucravacitinib 6 mg once daily in adult Japanese patients with PP, GPP, or EP. The coprimary endpoints were the proportion of patients achieving a ≥75% reduction from baseline in the Psoriasis Area and Severity Index (PASI 75) and a static Physician's Global Assessment score of 0 (clear) or 1 (almost clear) (sPGA 0/1) with at least a two-point improvement from baseline at week 16. Nonresponder imputation was used for missing data. Efficacy responses, adverse events (AEs), and serious AEs (SAEs) were recorded for up to 52 weeks. Seventy-four patients were treated (PP, n = 63; GPP, n = 3; EP, n = 8). At week 16, 76.2%, 66.7%, and 37.5% of patients with PP, GPP, and EP, respectively, had achieved PASI 75, and 82.5%, 0.0%, and 50.0% had achieved sPGA 0/1. Responses were overall maintained through week 52. AEs occurred in 74.6% of patients with PP, 100% of patients with GPP, and 87.5% of patients with EP. The most common AEs were nasopharyngitis and acne. Rates of SAEs and discontinuations were low. There were no deaths. Deucravacitinib was effective and well tolerated in Japanese patients with moderate to severe PP and in a limited number of patients with GPP or EP.

Real-World Discontinuation and Switching Patterns for Interleukin-Inhibitor Treatments in Patients with Moderate-to-Severe Psoriasis in Japan.

INTRODUCTION: Patients with moderate-to-severe psoriasis (PsO) treated with interleukin (IL)-inhibitors may require treatment modification to achieve disease control. This study evaluated discontinuation and switching of IL-inhibitors for PsO patients in Japan. METHODS: Japan Medical Data Center claims (1/2005-5/2022) were used to identify patients with PsO diagnosis preceding a first IL-inhibitor claim (index date) with ≥ 6 months of eligibility prior. Treatment switch (claim for another biologic) and discontinuation (gap in care ≥ 150% of the days' supply of the preceding prescription) were assessed up to 24 months following initiation. Censored Kaplan-Meier time-to-event analyses calculated rates, and Cox proportional hazards models estimated hazard ratios (HRs) adjusting for baseline characteristics. RESULTS: The study included 1481 unique patients treated with brodalumab (BRO; n = 159), guselkumab (GUS; n = 360), ixekizumab (IXE; n = 279), risankizumab (RIS; n = 327), secukinumab (SEC; n = 366), tildrakizumab (n = 40; excluded due to limited data), and ustekinumab (UST; n = 262). At 12/24 months, 25.9%/38.6% of patients overall had discontinued their index IL-inhibitor and 13.5%/21.2% had switched to another biologic. Discontinuation at 12/24 months was lowest for RIS (11.2%/17.4%), followed by UST (17.9%/32.2%), IXE (27.0%/37.0%), GUS (29.8%/43.0%), SEC (35.6%/53.8%), and BRO (37.2%/47.2%). Switching showed a similar trend: RIS (5.7%/10.7%), UST (11.2%/19.9%), SEC (14.7%/25.7%), IXE (14.8%/21.5%), GUS (16.9%/23.2%), and BRO (19.7%/26.8%). HRs of discontinuation relative to RIS were 2.07 for UST, 2.59 for IXE, 2.70 for GUS, 3.65 for BRO, and 3.69 for SEC (all P ≤ 0.001). HRs of switching relative to RIS were 2.05 for IXE, 2.45 for GUS, 2.67 for SEC, 2.73 for UST, and 2.77 for BRO (all P ≤ 0.01). CONCLUSION: Treatment modification of IL-inhibitors for PsO was commonly observed and could indicate insufficient disease control and/or incremental economic burden. Discontinuation and switching rates were lowest for RIS regardless of time point and adjustment for patient characteristics.

Mature IL-36γ Induces Stratum Corneum Exfoliation in Generalized Pustular Psoriasis by Suppressing Corneodesmosin.

Loss-of-function sequence variations in the IL36RN gene encoding IL-36 receptor antagonist cause familial generalized pustular psoriasis, which begins shortly after birth and is difficult to treat, and its effects on the epidermis are unclear. This study investigated the involvement of IL-36 receptor agonists in the epidermal formation of generalized pustular psoriasis. We found that the IL-36 receptor agonists, especially mature IL-36γ, stimulated IL-8 and pro-IL-36γ production in the epidermis while downregulating the genes encoding epidermal cornified envelope-related proteins, for example, corneodesmosin. IL-36 receptor antagonist and monoclonal anti-IL-36γ antibodies counteracted the effect of mature IL-36γ on corneodesmosin in keratinocytes in a dose-dependent manner. In the epidermis of patients with generalized pustular psoriasis with IL36RN loss-of-function sequence variations, pro-IL-36γ was overproduced in the epidermis, and corneodesmosin protein expression was markedly decreased in the region of giant subcorneal pustules (Kogoj's spongiform pustules), with high neutrophil infiltration. IL-8 induced by mature IL-36γ stimulated the infiltration of several neutrophils in the epidermis. The newly produced pro-IL-36γ is cleaved to the mature form by neutrophil proteases. This newly produced mature IL-36γ was predicted to further suppress the gene expression of corneodesmosin, leading to significant stratum corneum exfoliation and formation of the pustules. Overall, our results elucidate the mechanism underlying the formation of Kogoj's spongiform pustules in generalized pustular psoriasis.

Expression of laminin332 γ2 at the invasive front is associated with tumor budding and poor prognosis in cutaneous squamous cell carcinoma.

Laminin332 is a glycoprotein consisting of α3/ß3/γ2 chains, of which the γ2 chain (Ln-γ2) is expressed in tumor cells at the invasive front in many types of malignant tumors. We have previously reported that Ln-γ2 is associated with tumor invasion of cutaneous squamous cell carcinoma (cSCC) in vivo and in vitro. Recently, tumor budding (TB; invasion patterns in small clusters of less than five cancer cells in the stroma at the invasive front) has been reported to be a risk factor for lymph node metastasis in cSCC. Based on these findings, we speculated that expression of Ln-γ2 is related to TB in cSCC and would be an invasive factor that causes lymph node metastasis. In this study, we investigated the relationship between Ln-γ2 expression and clinicopathological findings, including TB, in 102 cases of cSCC using immunohistochemistry. The results showed that high expression of Ln-γ2 at the invasive front correlated with a high TB score. In addition, high Ln-γ2 expression at the invasive front was also associated with lymphatic invasion, lymph node metastasis, and poor prognosis (death or recurrence), as in TB. Furthermore, we showed a positive association between Ln-γ2 expression at the invasive front and Yes-associated protein (YAP) expression in the Hippo pathway. Our results suggest that Ln-γ2 expression at the invasive front may have a role in TB formation via YAP and contribute to prognosis by causing lymphatic invasion and lymph node metastasis. The expression of Ln-γ2 would be useful for risk assessment of lymph node metastasis and poor prognosis in routine practice of cSCC.

Real-world retention rates and effectiveness of secukinumab in psoriasis: Results from a multicenter cohort study (RAILWAY).

Psoriasis is a chronic, immune-mediated inflammatory skin disease with a high negative impact on patient's quality of life. Secukinumab, the first interleukin 17A inhibitor, has been used for the systemic treatment of psoriasis, but its long-term, real-world retention rates in Japan have not been fully investigated. In this multicenter, noninterventional, retrospective chart review study, the retention rate of secukinumab and its effectiveness among patients with psoriasis in Japan was evaluated up to 5 years. Data of patients who received secukinumab after December 26, 2014, were collected from medical charts obtained from seven sites, all certified for biologics use by the Japanese Dermatological Association. Patient characteristics, secukinumab retention, factors affecting secukinumab retention, reason for drug discontinuation, and effectiveness data were collected. The primary end point was secukinumab retention rate at week 52. A total of 123 patients were included in the analysis. Of these, 27 patients discontinued secukinumab by week 52, yielding a 78.0% (95% confidence interval, 69.6-84.4) retention rate at week 52. For patients whose Psoriasis Area and Severity Index (PASI) score was available, mean ± standard deviation PASI at baseline and at week 52 were 9.21 ± 7.37 and 1.4 ± 2.6, respectively. During the entire study period, "insufficient response" was the most common reason for discontinuation, and "history of biologics use" was a factor significantly associated with secukinumab discontinuation (hazard ratio, 1.72; p = 0.018). This study demonstrates the real-world retention rate and effectiveness of secukinumab in patients with psoriasis in Japan for up to 5 years and provides clinical insights into psoriasis treatment strategies.

English version of Japanese guidance for biologics in treating atopic dermatitis.

This is the English version of the Japanese guidance for biologics in treating atopic dermatitis (AD). The signaling pathway mediated by interleukin (IL)-4 and IL-13 contributes to type 2 inflammatory responses and plays an important role in the pathogenesis of AD. IL-31 is a cytokine mainly produced by activated T cells and is known to be involved in the pruritus of AD. Biologics for AD have been approved, including dupilumab, an anti-IL-4 receptor α antibody that was approved for expanded use in AD in 2018. In 2022, nemolizumab, an anti-IL-31 receptor α antibody, was approved for pruritus of AD, and tralokinumab, an anti-IL-13 antibody, was approved for AD. Physicians who intend to use these drugs should sufficiently understand and comply with the contents of the guidelines prepared by the Japanese Ministry of Health, Labour, and Welfare to promote the optimal use of the drugs. In treatment with biologics, it is important to consider disease factors (activity and severity), treatment factors (dosage and administration as well as the efficacy and safety), and patients' background characteristics (age and comorbidities) and share this information with patients when choosing treatment options. This guidance was developed for board-certified dermatologists who specialize in treating AD, and for promoting the proper use of biologics, taking into account the variety of factors in individual patients.

Efficacy and Safety of Apremilast for the Treatment of Japanese Patients with Palmoplantar Pustulosis: Results from a Phase 2, Randomized, Placebo-Controlled Study.

BACKGROUND: Palmoplantar pustulosis (PPP) is a pruritic, painful, recurrent, and chronic dermatitis with limited therapeutic options. OBJECTIVE: To evaluate the efficacy and safety of apremilast for the treatment of Japanese patients with PPP and inadequate response to topical treatment. METHODS: This phase 2, randomized, double-blind, placebo-controlled study enrolled patients with Palmoplantar Pustulosis Area and Severity Index (PPPASI) total score ≥ 12 and moderate or severe pustules/vesicles on the palm or sole (PPPASI pustule/vesicle severity score ≥ 2) at screening and baseline with an inadequate response to topical treatment. Patients were randomized (1:1) to apremilast 30 mg twice daily or placebo for 16 weeks, followed by a 16-week extension phase during which all patients received apremilast. The primary endpoint was achievement of PPPASI-50 response (≥ 50% improvement from baseline in PPPASI). Key secondary endpoints included change from baseline in PPPASI total score, Palmoplantar Pustulosis Severity Index (PPSI), and patient's visual analog scale (VAS) for PPP symptoms (pruritus and discomfort/pain). RESULTS: A total of 90 patients were randomized (apremilast: 46; placebo: 44). A significantly greater proportion of patients achieved PPPASI-50 at week 16 with apremilast versus placebo (P = 0.0003). Patients receiving apremilast showed greater improvement in PPPASI at week 16 versus placebo (nominal P = 0.0013), as well as PPSI and patient-reported pruritus and discomfort/pain (nominal P ≤ 0.001 for all). Improvements were sustained through week 32 with apremilast treatment. The most common treatment-emergent adverse events included diarrhea, abdominal discomfort, headache, and nausea. CONCLUSIONS: Apremilast treatment demonstrated greater improvements in disease severity and patient-reported symptoms versus placebo at week 16 in Japanese patients with PPP with sustained improvements through week 32. No new safety signals were observed. CLINICALTRIALS: GOV: NCT04057937.

English version of Japanese guidance for the use of oral Janus kinase inhibitors (JAK1 and TYK2 inhibitors) in the treatments of psoriasis.

This is the English version of Japanese guidance for the use of oral Janus kinase (JAK) inhibitors (JAK1 and tyrosine kinase 2 [TYK2] inhibitors) in the treatments of psoriasis. Several cytokines, such as interleukin (IL)-6, IL-7, IL-12, IL-21, IL-22, IL-23, interferon (IFN)-α, and IFN-γ, are involved in the pathogenesis of psoriasis (including psoriatic arthritis). As oral JAK inhibitors hinder the JAK-signal transducers and activators of transcription signal transduction routes involved in the signal transduction of these cytokines, they may be effective for the treatment of psoriasis. JAK has four types: JAK1, JAK2, JAK3, and TYK2. Regarding the use of oral JAK inhibitors for the treatment of psoriasis in Japan, indications of the JAK1 inhibitor upadacitinib were extended also to psoriatic arthritis in 2021, and the use of the TYK2 inhibitor deucravacitinib for plaque-type psoriasis, pustular psoriasis, and erythrodermic psoriasis became covered by health insurance in 2022. This guidance was developed for board-certified dermatologists who specialize in the treatment of psoriasis and to promote the proper use of oral JAK inhibitors. In the package inserts and guides for appropriate use, upadacitinib and deucravacitinib are classified as a "JAK inhibitor" and a "TYK2 inhibitor", respectively, and it is possible that there may be differences in safety between the two drugs. The safety of these drugs will be evaluated for the future by the postmarketing surveillance for molecularly targeted drugs for psoriasis of the Japanese Dermatological Association.

Treatment of plaque psoriasis with deucravacitinib (POETYK PSO-1 study): a plain language summary.

WHAT IS THIS SUMMARY ABOUT?: This is a summary of a paper published in a medical journal that describes the results of a study called POETYK PSO-1, which looked at a new treatment called deucravacitinib for plaque psoriasis. Plaque psoriasis appears on the body as round or oval raised patches (called plaques) typically covered by scales. This can cause the skin to itch, crack or bleed, and the associated itching and pain can make it difficult to perform basic everyday tasks. Living with psoriasis can cause emotional distress. Treatments are available, but some do not always reduce the symptoms of psoriasis, some may need to be injected or taken multiple times a day, and some may have side effects. Researchers are looking for new treatments that are more effective, convenient to take, and have acceptable safety and tolerability. WHAT HAPPENED IN THE STUDY?: Deucravacitinib is a once-daily pill taken by mouth (orally) that was studied as a treatment for moderate to severe plaque psoriasis in adults in two large studies conducted globally, PSO-1 and PSO-2. The POETYK PSO-1 study compared deucravacitinib with placebo (an inactive pill designed to have no effect) and an approved psoriasis treatment called apremilast, which is a pill taken twice a day. These were tested in adults with moderate to severe plaque psoriasis, which involved 10% or more of their body (equal to 10 or more handprints). The aim of the study was to compare the ability of deucravacitinib with placebo or apremilast to improve psoriasis for the people in the study, and to compare side effects that people had. WHAT DO THE RESULTS OF THE POETYK PSO-1 STUDY SHOW?: After 4 months of treatment, more people taking deucravacitinib had improvements in psoriasis plaques and skin appearance than those taking placebo or apremilast. The study also showed that people continued to see these improvements after taking deucravacitinib for up to 1 year. Side effects are events that happened during the study treatment phase that may or may not be caused by that treatment. Side effects for people taking deucravacitinib were generally mild and occurred in similar numbers overall to those in people taking placebo. The most common side effects in people taking deucravacitinib were inflammation or infection of the nasal (nose) passages and throat. Clinical Trial Registration: NCT03624127 (POETYK PSO-1 study) (ClinicalTrials.gov).

Efficacy and Safety of Tralokinumab in Adolescents With Moderate to Severe Atopic Dermatitis: The Phase 3 ECZTRA 6 Randomized Clinical Trial.

Importance: Safe and effective long-term treatments for adolescents with moderate to severe atopic dermatitis (AD) are limited. Objective: To evaluate the efficacy and safety of interleukin-13-targeted treatment with tralokinumab monotherapy in adolescents with AD. Design, Setting, and Participants: The 52-week, randomized, double-blinded, placebo-controlled, phase 3 ECZTRA 6 trial was conducted from July 17, 2018, through March 16, 2021, at 72 centers across 10 countries in North America, Europe, Asia, and Australia. Enrolled patients were 12 to 17 years old with moderate to severe AD (Investigator's Global Assessment [IGA] score ≥3; Eczema Area and Severity Index [EASI] ≥16). Interventions: Patients were randomized (1:1:1) to tralokinumab (150 or 300 mg) or placebo every 2 weeks for 16 weeks. Patients with an IGA score of 0 (clear) or 1 (almost clear) and/or 75% or higher improvement in EASI (EASI 75) at week 16 without rescue medication received maintenance treatment; other patients switched to open-label tralokinumab, 300 mg, every 2 weeks. Main Outcomes and Measures: Primary end points at week 16 were an IGA score of 0 or 1 and/or achieving EASI 75. Key secondary end points were a reduction of Adolescent Worst Pruritus Numeric Rating Scale of 4 or more, change in SCORing AD, and change in Children's Dermatology Life Quality Index from baseline to week 16. Safety end points were the number of adverse events and serious adverse events. Results: Of 301 patients randomized, 289 comprised the full analysis set (median [IQR] age, 15.0 [13.0-16.0] years; 149 [51.6%] male). More patients receiving tralokinumab, 150 mg, (n = 98), and tralokinumab, 300 mg (n = 97), achieved an IGA score of 0 or 1 without rescue medication at week 16 (21 [21.4%] and 17 [17.5%], respectively) vs placebo (n = 94; 4 [4.3%]) (adjusted difference, 17.5% [95% CI, 8.4%-26.6%]; P < .001 and 13.8% [95% CI, 5.3%-22.3%]; P = .002, respectively). More patients receiving tralokinumab, 150 mg (28 [28.6%]), and tralokinumab, 300 mg, (27 [27.8%]) vs placebo (6 [6.4%]) achieved EASI 75 without rescue at week 16 (adjusted difference, 22.5% [95% CI, 12.4%-32.6%]; P < .001 and 22.0% [95% CI, 12.0%-32.0%]; P < .001, respectively). Proportions of patients with Adolescent Worst Pruritus Numeric Rating Scale reduction of 4 or more from baseline were greater with tralokinumab, 150 mg (23.2%), and tralokinumab, 300 (25.0%), vs placebo (3.3%), and adjusted mean changes were greater in SCORing AD with tralokinumab, 150 mg (-27.5), and tralokinumab, 300 mg (-29.1), vs placebo (-9.5) and in Children's Dermatology Life Quality Index with tralokinumab, 150 mg (-6.1), and tralokinumab, 300 mg (-6.7), vs placebo (-4.1) at week 16. At week 52, tralokinumab efficacy was maintained without rescue in more than 50% of patients meeting primary end point(s) at week 16. In the open-label phase, IGA score of 0 or 1 and EASI 75 were achieved in 33.3% and 57.8%, respectively, at week 52. Tralokinumab was well tolerated, without frequency of conjunctivitis increasing through week 52. Conclusions and Relevance: In this randomized clinical trial, tralokinumab was efficacious and well tolerated, supporting its value for treating adolescents with moderate to severe AD. Trial Registration: ClinicalTrials.gov Identifier: NCT03526861.

Hepatitis C Virus-associated Cryoglobulinemic Livedo Reticularis Improved with Direct-acting Antivirals.

We herein report a case of hepatitis C virus (HCV)-associated cryoglobulinemic livedo reticularis in a woman in her 60s that improved with direct-acting antivirals (DAAs). Hyperpigmentation was observed in both lower legs, and a skin biopsy confirmed livedo reticularis, suggesting a relationship with cryoglobulinemia and HCV infection. DAAs with an NS5A inhibitor+NS3/4A protease inhibitor (glecaprevir/pibrentasvir) were administered for eight weeks, and a sustained virological response (SVR) was obtained. The disappearance of serum cryoglobulin was confirmed approximately two years after an SVR was obtained and livedo reticularis was improved. DAA therapy can be an effective therapeutic option for extrahepatic complications associated with HCV infection.