Generalized pustular psoriasis is a potentially life‐threatening neutrophilic skin disease characterized by recurrent flares of widespread erythema and eruption of sterile pustules. In the Effisayil™ ...1 study (NCT03782792), 53 patients with a generalized pustular psoriasis flare were treated with placebo or spesolimab, a humanized anti‐interleukin‐36 receptor monoclonal antibody, the first targeted treatment to be studied in a randomized clinical trial. Spesolimab treatment resulted in rapid pustular and skin clearance, with an acceptable safety profile. Here, we evaluate the efficacy and safety of spesolimab in 29 Asian patients in the Effisayil™ 1 study. The primary endpoint, a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustulation subscore of 0 (no visible pustules) at Week 1, was achieved by 10 patients (62.5%) randomized to spesolimab and one patient (7.7%) randomized to placebo (risk difference 54.8, 95% confidence interval CI 17.3–79.8). The key secondary endpoint, a GPPGA total score of 0 or 1 (clear or almost clear skin) at Week 1, was achieved by eight (50.0%) and two (15.4%) patients, respectively (risk difference 34.6, 95% CI −3.1–64.7). This was similar to previously published data in the overall population in whom the primary and key secondary endpoints were achieved by 54% versus 6% and 43% versus 11% of patients, respectively. The percentages of Asian patients randomized to spesolimab with a GPPGA pustulation subscore of 0 and GPPGA total score of 0 or 1 were sustained above 60% for up to 12 weeks. In these patients, patient‐reported outcomes also improved and markers of systemic inflammation were normalized. Eleven (68.8%) and eight (61.5%) of spesolimab‐ and placebo‐treated patients, respectively, experienced at least one adverse event. In conclusion, spesolimab improved outcomes in Asian patients compared with placebo, supporting its use in the treatment of generalized pustular psoriasis flares.
Juvenile generalized pustular psoriasis (GPP) is rare and often resistant to conventional systemic therapy such as methotrexate, retinoic acid and cyclosporin A. GPP can be induced by deficiency of ...interleukin (IL)-36 receptor antagonist (DITRA). No standardized guidelines are available for juvenile GPP or DITRA, and a uniformly safe and effective biologic agent has not been identified. However, multiple biologics approved for use in plaque-type psoriasis have also been used in GPP. Herein, we report a case of a 6-year-old Taiwanese boy with GPP and homozygous mutation at c.115+6T>C within the IL-36 receptor antagonist (IL36RN) gene, who was treated successfully with secukinumab after failure of prior methotrexate, acitretin, cyclosporin A, etanercept and adalimumab. Similar to two previously reported non-adult cases of GPP successfully treated with secukinumab, our case also demonstrated a history of repeated treatment failures with several conventional oral systemic agents and biologics. Different from these two cases, however, ours is the first of juvenile GPP successfully treated with secukinumab monotherapy, without using other systemic agent concurrently during the use of secukinumab.
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.
We report a seven‐patient case series of elderly‐onset generalized pustular psoriasis. These cases showed a high percentage of erythroderma, atypical clinical courses and a lower frequency of IL‐36RN c.115+6T>C mutation.
Background Secukinumab demonstrated superior efficacy to ustekinumab at week 4 and week 16 of the CLEAR study, with comparable safety, in subjects with moderate-to-severe plaque psoriasis. Objective ...To compare the efficacy and safety of secukinumab and ustekinumab use over 52 weeks. Methods Analysis of 52-week data from CLEAR, a randomized, double-blind, phase 3b study. Results Among 676 randomized subjects, secukinumab demonstrated superiority to ustekinumab at week 52 in the proportion of subjects with ≥90% improvement in Psoriasis Area and Severity Index (PASI 90) (76% vs 61% P < .0001); PASI 100 responses were 46% versus 36% ( P = .0103) and Investigator's Global Assessment responses of clear/almost clear skin were 80% versus 65% ( P < .0001). Subjects on secukinumab reported greater reductions in psoriasis-related pain, itching, and scaling, and greater improvement across all quality-of-life measures evaluated (Dermatology Life Quality Index DLQI, EuroQoL 5-Dimension Health Questionnaire, Work Productivity and Activity Impairment Questionnaire-Psoriasis, and Health Assessment Questionnaire-Disability Index). At week 52, 72% of subjects on secukinumab versus 59% on ustekinumab ( P = .0008) reported no impact of skin disease on their lives (DLQI 0/1 response). Safety and tolerability was comparable. Limitations There was no placebo arm. Conclusion In this head-to-head, double-blind study, secukinumab demonstrated sustained superior efficacy in comparison with ustekinumab in clearing skin through week 52, greater improvement in quality of life, and a favorable and comparable safety profile.
Background Secukinumab, a fully human anti–interleukin-17A monoclonal antibody, has demonstrated efficacy and safety in patients with moderate to severe plaque psoriasis. Objective We reviewed safety ...data from the secukinumab psoriasis phase II/III program. Methods Data were pooled from 10 phase II/III secukinumab psoriasis studies. Results Analysis included 3993 subjects; 3430 received secukinumab, representing 2725 subject-years (SYs) of exposure. Over 52 weeks, for secukinumab 300 mg, 150 mg, and etanercept, respectively, exposure-adjusted incidence rates (IRs) per 100 SYs were comparable across treatments for total adverse events (AEs; 236.1, 239.9, and 243.4, respectively); infections (91.1, 85.3, and 93.7, respectively); serious AEs (7.4, 6.8, and 7.0, respectively); serious infections (1.4, 1.1, and 1.4, respectively); malignant or unspecified tumors (0.77, 0.97, and 0.68, respectively); and adjudicated major adverse cardiovascular events (0.42, 0.35, and 0.34, respectively). AEs were not dose-related except for nonserious, mild/moderate, skin/mucosal candidiasis (IRs 3.55, 1.85, and 1.37 for secukinumab 300 mg, 150 mg, and etanercept, respectively). Limitations There was a limited number of patients in comparator groups and the exposure to placebo was short. Conclusion Secukinumab had a favorable safety profile, had no meaningful difference between the 300- and 150-mg doses and, in terms of safety, was comparable to etanercept over 52 weeks in patients with moderate to severe plaque psoriasis.
We retrospectively analyzed 66 patients with palmoplantar pustulosis (PPP) from January 1994 to September 2019 in our department. Interleukin-36 receptor antagonist gene (IL36RN) intron 3 c.115+6T>C ...mutation was present in two out of 27 patients (7.4%). Both cases developed generalized pustular psoriasis and/or acrodermatitis continua of Hallopeau later. Topical medications and phototherapy were used in 93.9% and 28.8% of patients, respectively, while 60.6% received systemic agents. The majority of patients (60.6%) responded to treatment, but episodes of flare-up existed. The demographic data of our patients with PPP showed female predominance (59.1%), middle-age onset (44.2 years old) and current smokers (62.1%). Generalized pustular psoriasis initially presenting as palmoplantar lesions may be misdiagnosed as PPP, and the presence of IL36RN mutation may serve to predict or confirm the diagnosis of future generalized pustular psoriasis or acrodermatitis continua of Hallopeau. To our knowledge, this is the largest demographic study of PPP in Taiwan.
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.
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.
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.
