Efficacy and safety of subcutaneous spesolimab for the prevention of generalised pustular psoriasis flares (Effisayil 2): an international, multicentre, randomised, placebo-controlled trial.

BACKGROUND: Spesolimab is an anti-interleukin-36 receptor monoclonal antibody approved to treat generalised pustular psoriasis (GPP) flares. We aimed to assess the efficacy and safety of spesolimab for GPP flare prevention. METHODS: This multicentre, randomised, placebo-controlled, phase 2b trial was done at 60 hospitals and clinics in 20 countries. Eligible study participants were aged between 12 and 75 years with a documented history of GPP as per the European Rare and Severe Psoriasis Expert Network criteria, with a history of at least two past GPP flares, and a GPP Physician Global Assessment (GPPGA) score of 0 or 1 at screening and random assignment. Patients were randomly assigned (1:1:1:1) to receive subcutaneous placebo, subcutaneous low-dose spesolimab (300 mg loading dose followed by 150 mg every 12 weeks), subcutaneous medium-dose spesolimab (600 mg loading dose followed by 300 mg every 12 weeks), or subcutaneous high-dose spesolimab (600 mg loading dose followed by 300 mg every 4 weeks) over 48 weeks. The primary objective was to demonstrate a non-flat dose-response curve on the primary endpoint, time to first GPP flare. FINDINGS: From June 8, 2020, to Nov 23, 2022, 157 patients were screened, of whom 123 were randomly assigned. 92 were assigned to receive spesolimab (30 high dose, 31 medium dose, and 31 low dose) and 31 to placebo. All patients were either Asian (79 [64%] of 123) or White (44 [36%]). Patient groups were similar in sex distribution (76 [62%] female and 47 [38%] male), age (mean 40·4 years, SD 15·8), and GPP Physician Global Assessment score. A non-flat dose-response relationship was established on the primary endpoint. By week 48, 35 patients had GPP flares; seven (23%) of 31 patients in the low-dose spesolimab group, nine (29%) of 31 patients in the medium-dose spesolimab group, three (10%) of 30 patients in the high-dose spesolimab group, and 16 (52%) of 31 patients in the placebo group. High-dose spesolimab was significantly superior versus placebo on the primary outcome of time to GPP flare (hazard ratio [HR]=0·16, 95% CI 0·05-0·54; p=0·0005) endpoint. HRs were 0·35 (95% CI 0·14-0·86, nominal p=0·0057) in the low-dose spesolimab group and 0·47 (0·21-1·06, p=0·027) in the medium-dose spesolimab group. We established a non-flat dose-response relationship for spesolimab compared with placebo, with statistically significant p values for each predefined model (linear p=0·0022, emax1 p=0·0024, emax2 p=0·0023, and exponential p=0·0034). Infection rates were similar across treatment arms; there were no deaths and no hypersensitivity reactions leading to discontinuation. INTERPRETATION: High-dose spesolimab was superior to placebo in GPP flare prevention, significantly reducing the risk of a GPP flare and flare occurrence over 48 weeks. Given the chronic nature of GPP, a treatment for flare prevention is a significant shift in the clinical approach, and could ultimately lead to improvements in patient morbidity and quality of life. FUNDING: Boehringer Ingelheim.

Trial of Spesolimab for Generalized Pustular Psoriasis.

BACKGROUND: Generalized pustular psoriasis (GPP) is a rare, life-threatening, inflammatory skin disease characterized by widespread eruption of sterile pustules. Interleukin-36 signaling is involved in the pathogenesis of this disorder. Spesolimab, a humanized anti-interleukin-36 receptor monoclonal antibody, is being studied for the treatment of GPP flares. METHODS: In a phase 2 trial, we randomly assigned patients with a GPP flare in a 2:1 ratio to receive a single 900-mg intravenous dose of spesolimab or placebo. Patients in both groups could receive an open-label dose of spesolimab on day 8, an open-label dose of spesolimab as a rescue medication after day 8, or both and were followed to week 12. The primary end point was a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustulation subscore of 0 (range, 0 [no visible pustules] to 4 [severe pustulation]) at the end of week 1. The key secondary end point was a GPPGA total score of 0 or 1 (clear or almost clear skin) at the end of week 1; scores range from 0 to 4, with higher scores indicating greater disease severity. RESULTS: A total of 53 patients were enrolled: 35 were assigned to receive spesolimab and 18 to receive placebo. At baseline, 46% of the patients in the spesolimab group and 39% of those in the placebo group had a GPPGA pustulation subscore of 3, and 37% and 33%, respectively, had a pustulation subscore of 4. At the end of week 1, a total of 19 of 35 patients (54%) in the spesolimab group had a pustulation subscore of 0, as compared with 1 of 18 patients (6%) in the placebo group (difference, 49 percentage points; 95% confidence interval [CI], 21 to 67; P<0.001). A total of 15 of 35 patients (43%) had a GPPGA total score of 0 or 1, as compared with 2 of 18 patients (11%) in the placebo group (difference, 32 percentage points; 95% CI, 2 to 53; P = 0.02). Drug reactions were reported in 2 patients who received spesolimab, in 1 of them concurrently with a drug-induced hepatic injury. Among patients assigned to the spesolimab group, infections occurred in 6 of 35 (17%) through the first week; among patients who received spesolimab at any time in the trial, infections had occurred in 24 of 51 (47%) at week 12. Antidrug antibodies were detected in 23 of 50 patients (46%) who received at least one dose of spesolimab. CONCLUSIONS: In a phase 2 randomized trial involving patients with GPP, the interleukin-36 receptor inhibitor spesolimab resulted in a higher incidence of lesion clearance at 1 week than placebo but was associated with infections and systemic drug reactions. Longer and larger trials are warranted to determine the effect and risks of spesolimab in patients with pustular psoriasis. (Funded by Boehringer Ingelheim; Effisayil 1 ClinicalTrials.gov number, NCT03782792.).

Acquired diffuse palmoplantar erythema with keratoderma in Chinese patients with pustular psoriasis: A predictor for IL36 receptor antagonist c.115+6T>C mutation?

Several studies have suggested that mutation of the interleukin 36 receptor antagonist gene (IL36RN) is related to generalized pustular psoriasis (GPP), and the presence of IL36RN mutation may affect the clinical manifestations and treatment responses. However, genetic testing is not routinely available in clinical practice for the diagnosis of GPP. Previously, GPP patients with acrodermatitis continua of Hallopeau (ACH) were found to have a high percentage of carrying IL36RN mutation. In this study, we reported six patients with pustular psoriasis presenting as diffuse palmoplantar erythema with keratoderma among 60 patients who carried IL36RN mutation. ACH was present in five patients and five patients had acute flare of GPP. This unique presentation may serve as a predictor for IL36RN mutation in patients with pustular psoriasis, similar to ACH.

Deficiency of interleukin-36 receptor antagonist (DITRA): An analysis of 58 Chinese patients in a tertiary hospital in Taiwan.

DITRA, acronym for deficiency of interleukin-36 receptor antagonist (IL36RN), leads to unopposed pro-inflammatory signalling which typically manifests as pustular psoriasis. In Asian patients, c.115 + 6 T > C mutation is the most common and important single-nucleotide variant in DITRA. We present the largest case series consisting of 58 DITRA patients carrying heterozygous or homozygous c.115 + 6 T > C mutation. The mean age of onset (±SD) was 20.74 (±20.86), and the median age of onset was 13 years old. Twelve patients (20.7%) had disease onset before the age of two. Twenty-two patients (37.9%) had disease onset between the ages of 2-18. Main clinical phenotype was generalized pustular psoriasis (GPP) with systemic symptoms (33 patients, 56.9%), followed by acrodermatitis continua of Hallopeau (ACH) (16 patients, 27.6%). Nearly half of our patients (27 patients, 46.6%) ever had ACH, and only three of them are free of ACH currently, which indicates that the development of ACH is relatively persistent and irreversible. Thirty-four patients (58.6%) had recurrent GPP and 29 patients (50%) have been admitted due to GPP flare. Compared to those with heterozygous (C/T) mutation, more patients carrying homozygous mutation (C/C) have recurrent episodes of GPP (C/T vs. C/C: 25.53 vs. 76.47%, p = 0.0367). Two patients with squamous cell carcinomas arising from the pustular psoriasis skin lesions were noted. Two patients had elevated serum IgG4 levels.

Predictors for the effectiveness of 75 mg risankizumab in treating psoriasis-A real-word evidence from a 52-week retrospective study.

In the registration trial of risankizumab for patients with moderate-to-severe psoriasis in Japan, similar Psoriasis Area Severity Index (PASI) responses were observed for 75 mg or 150 mg risankizumab at most time points up to 52 weeks, except for PASI 100 at week 16. The use of 75 mg risankizumab offers an attractive option considering the high cost of risankizumab. However, it is unknown whether patients with mild-to-moderate psoriasis respond similarly, and the efficacy data of non-Japanese patients is also lacking. We retrospectively included 30 consecutive Chinese patients receiving half-dose (75 mg) risankizumab as scheduled up to 52 weeks. Compared with biologic-experienced group, biologic-naive group had a significantly higher PASI 50/75/90/100 achievement (p = 0.0098/0.0039/0.0016/0.0054) at week 52. PASI 50/75/90/100 curves in biologic-naive group (p = 0.0117/0.0239/0.0143/0.0269) were also significantly higher when analysed generalized estimating equations (GEE) model. Though there was no statistically significant difference in terms of PASI 50/75/90/100 responses at any time points between those with body weight ≦ 65 kg and those >65 kg, a tendency of secondary failure was noted in those >65 kg from week 40 onwards. Patients who were both biologic-naive and weighed ≦ 65 kg achieved sustained PASI 50/75/90 responses from week 16/28/40 onwards, respectively, indicating that they could be considered as potential candidates for 75 mg risankizumab. Though PASI 75 curve in patients without diabetes mellitus (DM) surpassed that in patient without DM, curves of other parameters did not reach significance when analysed by GEE model. There was no HBV, HCV or TB reactivation, nor other new safety signals during the 52-week observational period. Providing risankizumab with flexible dosing options is beneficial in clinical practice considering the high cost of this medication.

Secukinumab long-term efficacy and safety in psoriasis through to year 5 of treatment: results of a randomized extension of the phase III ERASURE and FIXTURE trials.

BACKGROUND: In the long-term extension study of the ERASURE and FIXTURE trials, the efficacy of secukinumab (a fully human anti-interleukin-17A monoclonal antibody) was demonstrated to have been maintained through to year 3 of treatment in moderate-to-severe plaque psoriasis. OBJECTIVES: To assess the efficacy and safety of secukinumab through to year 5 of treatment in moderate-to-severe plaque psoriasis. METHODS: Responders with ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) from two core trials - ERASURE and FIXTURE - were randomized 2 : 1 at year 1 (end of core trials) to either the same dose (300 or 150 mg, continuous treatment) or placebo (treatment withdrawal) every 4 weeks, until year 3 or relapse (> 50% reduction in maximal PASI from core study baseline). Partial responders (achieving PASI 50 but not PASI 75) at year 1 continued at the same dose as in the core trials. At year 3, all patients received open-label secukinumab treatment, with those on secukinumab 300 mg continuing on their dose, while those on secukinumab 150 mg or placebo received secukinumab 150 or 300 mg based on the physician's discretion. The study is registered on ClinicalTrials.gov with the identifier NCT01544595. RESULTS: Most patients randomized to placebo at year 1 relapsed, but the response was rapidly recaptured upon reinitiation of treatment. PASI responses were sustained with secukinumab through to year 5. The PASI responses for the 300 mg responders + partial responders group at year 1 (PASI 75/90/100: 86.8%/72.8%/45.9%) trended downwards until year 3 (PASI 75/90/100: 82.3%/58.4%/32.7%) and then remained stable through year 4 (PASI 75/90/100: 83.3%/60.1%/32.2%) until year 5 (PASI 75/90/100: 81.1%/62.8%/35.1%). Dermatology Life Quality Index showed sustained benefit up to year 5. Absolute PASI responses were maintained throughout the study. The most common adverse events (AEs) were infections and infestations, nasopharyngitis, and upper respiratory tract infections (URTIs). The overall exposure-adjusted incidence rate (EAIR; with 95% confidence interval) for all AEs was 139.9 (130.3-149.9). EAIRs for Crohn's disease and neutropenia were 0.1 (0.0-0.3) and 0.5 (0.3-0.8), respectively. CONCLUSIONS: The 4-year extension of two pivotal phase III trials demonstrated that secukinumab treatment was effective through to year 5 and improved quality of life in patients with moderate-to-severe plaque psoriasis. The most common AEs were infections and infestations, nasopharyngitis, and URTIs. The safety profile was consistent with that in the secukinumab phase II/III clinical development programme.

Predictors of time to relapse following ustekinumab withdrawal in patients with psoriasis who had responded to therapy: An 8-year multicenter study.

BACKGROUND: Data on predictors and time to relapse in patients with psoriasis who discontinue therapy in a real-world setting are scarce. OBJECTIVE: To investigate predictors of relapse after withdrawal of ustekinumab in patients with psoriasis. METHOD: This study screened 500 patients with psoriasis who received ustekinumab (669 treatment episodes) between 2011 and 2018. Overall, 202 patients (accounting for 304 treatment episodes) who had responded to therapy and were withdrawn from ustekinumab treatment were included. RESULTS: The cumulative probabilities of being relapse-free at 6, 12, 18, 24, and 36 months after withdrawal from ustekinumab treatment were 49.3%, 12.6%, 5.3%, 4.7%, and 1.6%, respectively. Multivariate regression analyses with a generalized estimating equation showed that after adjustments, biologic-naive status, maximum improvement in Psoriasis Area and Severity Index during ustekinumab treatment, time to achieve a 50% improvement in baseline Psoriasis Area and Severity Index score after initiation of ustekinumab, family history of psoriasis, chronic kidney disease, and immunosuppressant use while not taking ustekinumab were significant predictors of time to relapse following discontinuation of ustekinumab. LIMITATION: Nonrandomized allocation of duration of treatment and follow-up. CONCLUSION: Given the high rates of relapse, withdrawal of ustekinumab from patients with well-controlled psoriasis cannot be recommended.

Spesolimab improves patient-reported outcomes in patients with generalized pustular psoriasis: Results from the Effisayil 1 study.

BACKGROUND: Generalized pustular psoriasis (GPP) is a rare inflammatory skin disease with a considerable clinical burden. In the Effisayil™ 1 study, spesolimab, an anti-interleukin-36 receptor monoclonal antibody, demonstrated efficacy in treating GPP flares. OBJECTIVES: To evaluate patient-reported outcomes (PROs) of patients with GPP who were treated with intravenous (IV) spesolimab 900 mg in the Effisayil™ 1 study. METHODS: Fifty-three patients presenting with a GPP flare were randomized (2:1) to receive a single dose of IV spesolimab 900 mg or placebo and were followed for 12 weeks. Four PROs (pain visual analogue scale [pain VAS]; Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-Fatigue]; Dermatology Life Quality Index [DLQI]; and Psoriasis Symptom Scale [PSS]) were assessed throughout the 12-week study. Minimal clinically important differences (MCIDs) were defined. All data are reported descriptively. RESULTS: In patients who received spesolimab, improvements from baseline (median [Q1, Q3]) were observed in pain VAS (-21.3 [-55.3, -3.1]), FACIT-Fatigue (7.0 [1.0, 20.0]), DLQI (-2.5 [-8.0, 1.0]) and PSS (-4.0 [-7.0, 0.0]) within 1 week of treatment. These improvements were sustained over 12 weeks and corresponded to the achievement of MCIDs at Week 1, which were also sustained over 12 weeks. Patients in the placebo arm experienced improvements in PROs and achievement of MCIDs after receipt of open-label spesolimab at Week 1. CONCLUSIONS: Patients with a GPP flare treated with spesolimab achieved improvements in PROs by Week 1, which were sustained for 12 weeks, and achieved MCIDs as early as Week 1.

2022 Taiwanese Dermatological Association (TDA), Taiwanese Association for Psoriasis and Skin Immunology (TAPSI), and Taiwan Society of cardiology (TSOC) joint consensus recommendations for the management of psoriatic disease with attention to cardiovascular comorbidities.

Psoriatic disease is a chronic inflammatory disorder with skin and joint manifestations. Due to the persistent inflammatory state exhibited by patients with psoriasis, multiple systemic comorbidities occur more frequently in patients with psoriasis than in the general population, and the risk of cardiovascular (CV) diseases is significantly increased. As the pathophysiology of psoriatic disease is becoming better understood, the sharing of underlying pathogenic mechanisms between psoriatic and CV diseases is becoming increasingly apparent. Consequently, careful attention to CV comorbidities that already exist or may potentially develop is needed in the management of patients with psoriasis, particularly in the screening and primary prevention of CV disease and in treatment selection due to potential drug-drug and drug-disease interactions. Furthermore, as the use of effective biologic therapy and more aggressive oral systemic treatment for psoriatic disease is increasing, consideration of the potential positive and negative effects of oral and biologic treatment on CV disease is warranted. To improve outcomes and quality of care for patients with psoriasis, the Taiwanese Dermatological Association, the Taiwanese Association for Psoriasis and Skin Immunology, and the Taiwan Society of Cardiology established a Task Force of 20 clinicians from the fields of dermatology, cardiology, and rheumatology to jointly develop consensus expert recommendations for the management of patients with psoriatic disease with attention to CV comorbidities.

The Pressurized Skin: A Review on the Pathological Effect of Mechanical Pressure on the Skin from the Cellular Perspective.

Since human skin is the primary interface responding to external mechanical stimuli, extrinsic forces can disrupt its balanced microenvironment and lead to cutaneous lesions. We performed this review to delve into the pathological effects of mechanical pressure on skin from the cellular perspective. Fibroblasts of different subsets act as heterogeneous responders to mechanical load and express diverse functionalities. Keratinocytes relay mechanical signals through mechanosensitive receptors and the ensuing neurochemical cascades to work collaboratively with other cells and molecules in response to pressure. Mast cells release cytokines and neuropeptides, promoting inflammation and facilitating interaction with sensory neurons, while melanocytes can be regulated by pressure through cellular and molecular crosstalk. Adipocytes and stem cells sense pressure to fine-tune their regulations of mechanical homeostasis and cell differentiation. Applying mechanical pressure to the skin can induce various changes in its microenvironment that potentially lead to pathological alterations, such as ischemia, chronic inflammation, proliferation, regeneration, degeneration, necrosis, and impaired differentiation. The heterogeneity of each cellular lineage and subset from different individuals with various underlying skin conditions must be taken into consideration when discussing the pathological effects of pressure on the skin. Thus, elucidating the mechanotransduction and mechanoresponsive pathways from the cellular viewpoint is crucial in diagnosing and managing relevant dermatological disorders.

Aggravation of discoid lupus erythematosus in a patient with psoriasis and psoriatic arthritis during treatment of secukinumab: A case report and review of literature.

BACKGROUND: The coexistence of psoriasis and cutaneous lupus erythematosus (LE) is uncommon. Treatment for concomitant psoriasis and LE is challenging because some valid treatments for LE such as hydroxychloroquine and systemic corticosteroid are known to aggravate psoriasis. Th17 pathway is shared by these two disease entities. Thus, biologics targeting Th17 pathway, including ustekinumab and secukinumab, have been successfully used in the treatment of patients with concomitant psoriasis and LE. PURPOSE: We report a patient with aggravation of discoid lupus erythematosus (DLE) after secukinumab treatment for psoriasis. RESEACH DESIGN: Case report. STUDY SAMPLE: One patient was included in this case report. DATA COLLECTION AND ANALYSIS: Clinical and pathological pictures were presented after informed consent. RESULT: Symptoms of psoriasis and psoriatic arthritis almost resolved after 150 mg secukinumab every four weeks for 2 years, but lesions of DLE enlarged and became generalized. CONCLUSION: LE is a highly heterogeneous disease, and further studies are required to find the optimal treatment in patients suffering from both LE and psoriasis.

Non-immune functions of inflammatory cytokines targeted by anti-psoriatic biologics: a review.

PURPOSE: Psoriasis is an inflammatory disease characterized by skin thickening with silvery white desquamation due to dysregulated inflammatory pathways and elevated levels of inflammatory cytokines. Biologic agents targeting these inflammatory cytokines have brought about significant improvement in clearing psoriatic lesions in patients with moderate-to-severe psoriasis. Moreover, biologics exert both beneficial and detrimental effects on comorbidities in psoriasis, which include increased risk of cardiovascular events, metabolic syndrome, among other conditions. However, non-immune functions of cytokines targeted by biologics, and, hence, the potential risks and benefits of biologics for psoriasis to different organs/systems and comorbidities, have not been well elucidated. RESULTS: This review summarizes current understanding of the pathogenesis of psoriasis-related comorbidities and emerging discoveries of roles of cytokines targeted in psoriasis treatment, including tumor necrosis factor α and interleukins 12, 23, and 17, aiming to complete the safety profile of each biologics and provide therapeutic implications on psoriasis-related comorbidities, and on diseases involving other organs or systems.

Consistent safety profile with up to 5 years of continuous treatment with guselkumab: Pooled analyses from the phase 3 VOYAGE 1 and VOYAGE 2 trials of patients with moderate-to-severe psoriasis.

BACKGROUND: Guselkumab effectively treats moderate-to-severe psoriasis. OBJECTIVE: To evaluate the cumulative safety experience of guselkumab using pooled data from the VOYAGE 1 and 2 studies through 5 years. METHODS: Patients were randomized to guselkumab, placebo with crossover to guselkumab at week 16, or adalimumab. The studies were identical through week 24. VOYAGE 1 evaluated continuous guselkumab treatment (adalimumab-crossover-to-guselkumab at week 52), while VOYAGE 2 assessed randomized withdrawal/retreatment (weeks 28-76). Open-label guselkumab treatment was administered starting at week 52 in VOYAGE 1 and week 76 in VOYAGE 2 and continued through week 252. Pooled safety data were adjusted by exposure and analyzed in the guselkumab groups, including placebo-crossover-to-guselkumab (n = 1221) and adalimumab-crossover-to-guselkumab (n = 500), through week 264. RESULTS: Patients were followed for a total of 7166 patient-years (PY). Overall, 1349 of 1721 guselkumab-treated patients (78.4%) continued treatment through week 252. The rates of adverse and serious adverse events were 149/100 PY and 5.01/100 PY, respectively. Rates of adverse events of interest were low: serious infections (0.85/100 PY), nonmelanoma skin cancer (0.34/100 PY), malignancies other than nonmelanoma skin cancer (0.45/100 PY), and major adverse cardiovascular events (0.29/100 PY). Year-to-year variability was evident, but no increasing trend was observed. LIMITATIONS: No direct treatment comparisons were possible after week 52. CONCLUSION: The safety profile remained consistent and favorable during 5 years of continuous guselkumab treatment of psoriasis.

Time to Loss of Response following Withdrawal of Ixekizumab in Patients with Moderate-to-Severe Psoriasis.

In clinical practice, interruption of treatment may not result in immediate cessation of disease control, and some patients even experience sustained treatment response following treatment interruption. This post hoc analysis of UNCOVER-1 and -2 Phase 3 clinical trials characterized the time to loss of treatment response in patients with psoriasis who responded to ixekizumab through a 12-week treatment period, and who were then re-randomized to placebo for the following 48 weeks. For those with static Physician Global Assessment [sPGA]0/1 and Psoriasis Area and Severity Index [PASI]90 at Week 12, the median time to loss of PASI90 was 16.1 weeks (95% confidence interval 12.7-16.4). For those with PASI100 at Week 12, the median time to loss of PASI100 was 12.1 weeks (95% confidence interval 9.0-13.0). A small subset of patients maintained high levels of disease control through Week 60. This study adds to the growing body of evidence on sustained treatment response following treatment interruption.

Elderly-onset generalized pustular psoriasis: a case series.

Elderly-onset (> 60 years of age) atopic dermatitis and psoriasis have been reported to present special clinical phenotypes; however, the study of elderly-onset generalized pustular psoriasis (GPP) has been limited, mainly due to its rarity. Previous studies have shown that the mean age of GPP onset is around 40 years, and onset at > 60 years of age is extremely rare. We report a case series of seven patients with elderly-onset GPP. The clinical features of the seven patients were assessed, and all seven patient were analysed for presence of the c.115+6T>C mutation in the gene encoding for interleukin-36 receptor antagonist (IL36RN). These patients had an atypical clinical course and a lower frequency of the IL36RN c.115+6T>C mutation. IL36RN mutations may have a significant, dose-dependent effect on the onset age of GPP.

Comparative effectiveness of biologics in clinical practice: week 12 primary outcomes from an international observational psoriasis study of health outcomes (PSoHO).

BACKGROUND: Clinical trials study treatment outcomes under stringent conditions, capturing incompletely the heterogeneity of patient populations and treatment complexities encountered in real-world practice. OBJECTIVES: To compare the effectiveness of anti-interleukin (IL)-17A biologics relative to other approved biologics in patients with moderate-to-severe psoriasis. METHODS: The Psoriasis Study of Health Outcomes (PSoHO) is an ongoing 3-year observational cohort study in adults with chronic moderate-to-severe plaque psoriasis initiating or switching to a new biologic. Primary study endpoint is the proportion of patients achieving 90% improvement in Psoriasis Area and Severity Index (PASI 90) and/or static Physician Global Assessment (sPGA) 0/1 at Week 12 (W12) in the anti-IL-17A cohort (ixekizumab [IXE], secukinumab) vs. all other approved biologics. Secondary outcomes include the proportion of patients who achieve PASI 75/90/100, absolute PASI scores ≤5, ≤2 and ≤1, Dermatology Life Quality Index (DLQI) score of 0/1 at W12 between the two cohorts and among the individual biologics. Comparative effectiveness analyses were conducted using Frequentist Model Averaging (FMA), a novel causal inference machine learning approach. Missing data for binary outcomes were imputed as non-response. RESULTS: Patient profiles in the anti-IL-17A cohort and other biologics cohort were similar, with more frequent comorbid psoriatic arthritis and less frequent exposure to conventional treatments in the patients receiving anti-IL-17A biologics. At W12, 71.4% of patients who received an anti-IL-17A biologic achieved PASI 90 and/or sPGA 0/1 compared to 58.6% of patients who received other biologics (odds ratios [OR], 1.9; 95% confidence intervals [CI], [1.6, 2.4]). Similar findings were observed for secondary outcomes. CONCLUSIONS: These results reflect the high efficacy and early onset of skin clearance of IL-17A inhibitors observed in randomized clinical trials and confirm the effectiveness of anti-IL-17A biologics in the real-world setting.

Severity of periodontitis and salivary interleukin-1ß are associated with psoriasis involvement.

BACKGROUND/PURPOSE: Both psoriasis and periodontal diseases are characterized by an exaggerated immune response to the microbiota residing on epithelial surfaces. This study aimed to explore the associations between the severity of psoriasis and periodontal destruction in patients with psoriasis. METHODS: Thirty-three patients diagnosed with psoriasis were referred from the dermatology clinic of National Taiwan University Hospital. Full-mouth periodontal examination was performed and saliva was collected after patients signed informed consent forms. The Psoriasis Area Severity Index (PASI) as well as clinical periodontal parameters including probing depth (PD), plaque index (PI), gingival index (GI), and clinical attachment level (CAL) were evaluated. Salivary cytokines including interleukin (IL)-1ß, IL-12, IL-17, interferon-γ, and tumor necrosis factor (TNF)-α were tested with the Luminex Bio-Plex system. Anti-inflammatory medication, tobacco use, and underlying comorbidities were included in the analysis. RESULTS: Baseline PASI was significantly associated with PI. PASI at follow-up was positively correlated with CAL ≥ 4 mm (%) and saliva IL-1ß levels. Psoriasis patients who used non-steroidal anti-inflammatory drugs or topical steroids had significantly lower GI, PD ≥ 4 mm (%), and saliva IL-1ß and TNF-α levels. Moreover, a history of tobacco use was associated with higher PD ≥ 4 mm (%). CONCLUSION: PI, CAL, and salivary IL-1ß were associated with PASI. Periodontal severity was associated with psoriasis involvement. Periodontal inflammation in psoriasis may be modified by anti-inflammatory medication and tobacco use. Additional large-scale longitudinal and mechanistic studies are needed.

Taiwanese dermatological association consensus for the definition, classification, diagnosis, and management of urticaria: A 2021 update.

Urticaria is a prevalent disease with substantial physical, psychological, and economic impacts. With the advent of understandings of the disease and the emerging evidence of treatments, the international guidelines for treating urticaria have been updated in recent years. In order to update the 2014 edition of the Taiwanese Dermatological Association (TDA) consensus of urticaria, a total of 17 dermatologists with extensive experience in urticaria management were invited to and attended the TDA consensus meetings. All the specific aspects of the content were approved by at least 75% of the experts in attendance. Comparing to the former edition, several substantial modifications were made. For diagnosis, D-dimer was added as the recommended routine test in patients with chronic spontaneous urticaria. For pharmacological management, treatment suggestions were simplified. The approved-dosed, the up-dosed second-generation antihistamines, omalizumab, and cyclosporine were listed as the first-line to the fourth-line treatment, respectively. In addition, the management for patients of special considerations, such as the elderly, children, and pregnant women, were all discussed and mentioned in the consensus. We hope the updated TDA consensus can serve as a reference for all physicians and can help the physicians providing up-to-dated managements for these patients.

Overlapping Features of Psoriasis and Atopic Dermatitis: From Genetics to Immunopathogenesis to Phenotypes.

Psoriasis (PSO) and atopic dermatitis (AD) were once considered to be mutually exclusive diseases, but gradually regarded as a spectrum of disease. Shared genetic loci of both diseases were noted in some populations, including Chinese. Shared immunopathogenesis involving Th17, Th1, Th22 cells, or even IL-13 was found in certain stages or phenotypes. This review discusses the overlapping genetic susceptibility, shared cytokines, immune-mediated comorbidities, and clinical presentations. Overlapping conditions could be classified into mainly PSO lesions with AD features or vice versa, concomitant PSO and AD, or disease transformation as a result of biologics treatment.

Predictors of hepatitis B and C virus reactivation in patients with psoriasis treated with biologic agents: a 9-year multicenter cohort study.

BACKGROUND: The increasing use of biologics is accompanied by a risk of hepatitis B (HBV) and C virus (HCV) reactivation. OBJECTIVE: To determine the predictors of HBV and HCV reactivation in patients with psoriasis receiving biologics. METHODS: This study screened 2060 patients with psoriasis (3562 treatment episodes) who were taking biologics from 2009 to 2018. There were 359 patients with psoriasis with HBV (561 treatment episodes) and 61 with HCV infection (112 treatment episodes). RESULTS: During 8809 and 1522 person-months of follow-up, 88 treatment episodes for HBV involved HBV reactivation, and 14 episodes of HCV involved reactivation. The reactivation rate was significantly higher in treatment episodes of chronic HBV infection than in that of occult HBV (34.3% vs 3.2%, P = .001) and resolved HBV (34.3% vs 5.0%, P < .001). The multivariate analysis revealed that being hepatitis B surface antigen seropositive, being hepatitis B e-antigen seropositive, and tumor necrosis factor-α-inhibitor therapy were risk factors for HBV reactivation, whereas antiviral prophylaxis was effective in reducing the risk of HBV reactivation. No predictors were significantly associated with HCV reactivation. LIMITATIONS: Observational design and a lack of a comparison group. CONCLUSION: Patients with psoriasis on biologics have a risk of HBV and HCV reactivations, particularly those who are seropositive for hepatitis B surface antigen and hepatitis B e-antigen and undergoing tumor necrosis factor-α-inhibitor therapy.