Guselkumab,an anti‐interleukin‐23 monoclonal antibody,for the treatment of moderate to severe plaque‐type psoriasis in Japanese patients: Efficacy and safety results from a phase 3, randomized,double‐blind,placebo‐controlled study

Previous global studies of guselkumab have demonstrated clinical benefits in patients with psoriasis. The aim of this 52‐week, phase 3 study was to evaluate efficacy and safety of guselkumab in Japanese patients with moderate to severe plaque‐type psoriasis. Patients randomly received guselkumab 50 mg or 100 mg at weeks 0, 4 and every 8 weeks, or placebo with cross‐over to guselkumab 50 mg or 100 mg at week 16. Co‐primary end‐points were the proportion of patients achieving Investigator's Global Assessment (IGA) cleared/minimal (0/1) and 90% or more improvement in Psoriasis Area and Severity Index (PASI‐90) at week 16. Overall, 192 patients were randomized to placebo, guselkumab 50 mg or 100 mg. At week 16, patients in the placebo group were crossed over to guselkumab 50 mg or 100 mg. At week 16, a significantly (P < 0.001) higher proportion of patients receiving guselkumab 50 mg and 100 mg versus placebo achieved IGA 0/1 (92.3% and 88.9% vs 7.8%) and PASI‐90 (70.8% and 69.8% vs 0%). Patients in guselkumab 50 mg and 100 mg groups achieved significant improvement versus placebo in PASI‐75 (89.2% and 84.1% vs 6.3%, P < 0.001) at week 16; improvement was maintained through week 52. Incidences of treatment‐emergent adverse events were comparable among the groups through week 16; the most commonly reported was nasopharyngitis. No new safety concerns were observed until week 52. In conclusion, guselkumab treatment demonstrated superior efficacy over placebo and was well tolerated in Japanese patients with moderate to severe plaque‐type psoriasis.     

Safety of selective IL‐23p19 inhibitors for the treatment of psoriasis

Psoriasis is a chronic disease that requires long‐term treatment. Consequently, understanding the safety and tolerability of any potential treatment over time is critical to effective prescribing. The biologic agents currently available for the treatment of psoriasis target a number of different inflammatory cytokines involved in psoriasis disease pathogenesis. The monoclonal antibodies tildrakizumab, guselkumab and risankizumab target the p19 subunit that is specific to interleukin (IL)‐23. This article reviews published data on the safety of these IL‐23p19 inhibitors in patients with psoriasis compared with other currently available biologic therapies. Data from randomized, placebo‐ and active‐controlled phase 3 clinical trials show tildrakizumab, guselkumab and risankizumab to have a favourable risk–benefit profile in patients with moderate to severe psoriasis. No significant safety concerns have been observed for any of these IL‐23p19 inhibitors in the data published to date. The most commonly reported adverse events (AEs) associated with these agents in phase 3 studies were upper respiratory tract infections. No increase was seen in rates of serious infections, malignancies or major adverse cardiovascular events, with no signals suggestive of an elevated risk of opportunistic infections, active tuberculosis or reactivation of latent tuberculosis infection, mucocutaneous Candida infections, triggering or worsening of inflammatory bowel disease, demyelinating disorders or suicidal ideation. Selectively targeting IL‐23p19 may help avoid AEs that have been associated with biologic agents with other mechanisms of action. Data from long‐term extension studies and patient registries will further establish the safety profile of IL‐23p19 inhibitors for the treatment of moderate to severe psoriasis in routine practice.     

A case of erythrodermic psoriasis successfully treated with guselkumab

Erythrodermic psoriasis (EP) is the most severe form of psoriasis, resulting in significant morbidity and mortality. EP treatment with biologics is not well ruled by international guidelines, so most biological drugs are used basing on case reports or small case series. Guselkumab, a fully human anti‐interleukin (IL)‐23 monoclonal antibody, is approved for moderate to severe plaque psoriasis while its use in EP is off label. To date, no case reports on Caucasian patients have been described in the literature. We report the case of 38‐year‐old Caucasian male with EP successfully treated with guselkumab, reaching PASI 100 after 20 weeks of therapy and still maintaining this response at Week 48. Our case report suggests guselkumab as an efficacious and well‐tolerated treatment in EP, presenting a long‐term efficacy in the prevention of recurrences. Further studies are warrant to confirm our data, with controlled trials specifically dedicated to EP being strictly needed in order to verify the role and efficacy of anti‐IL23 in EP.     

Efficacy and safety of guselkumab in psoriasis patients who failed ustekinumab and/or anti‐interleukin‐17 treatment: A real‐life 52‐week retrospective study

Recent major research advancements have significantly expanded our understanding of psoriasis pathophysiology, resulting in the development of highly effective, targeted therapies. Guselkumab is the first interleukin (IL)‐23 inhibitor approved for the treatment of moderate‐to‐severe‐psoriasis, providing a new therapeutical option for psoriasis. The aim of our study was to evaluate the efficacy of guselkumab in psoriatic patients who previously failed anti‐IL‐12/23 and/or anti‐IL‐17 treatment. A 52‐week single‐center retrospective study was performed enrolling moderate‐to‐severe patients attending our Psoriasis Care Center from October 2018 to May 2020. Study population included 13 patients; 46.1% have been previously treated with ustekinumab, while 69.2% have previously failed an anti‐IL‐17 treatment (38.5% secukinumab, 30.8% ixekizumab, and 38.5% both). At baseline, mean Psoriasis Area and Severity Index was 13.2 ± 6.8, reducing up to 0.5 ± 0.7 at week 52 (P < .001). Body surface area reduced from 22.3 ± 10.5 (baseline) to 0.8 ± 1.1 at week 52 (P < .001). No statistically significant differences have been found between patients previously treated with anti‐IL‐12/23 compared to anti‐IL‐17 or both. Only one patient discontinued guselkumab at week 36 due to secondary inefficacy. This is a single institution study with a relatively small sample size. Our real‐life data confirm trial results, showing guselkumab as a safe and effective option in patients with moderate‐to‐severe psoriasis even in those who previously failed ustekinumab and/or anti‐IL‐17 treatment.     

Efficacy and safety of guselkumab in patients with psoriasis who have an inadequate response to ustekinumab: results of the randomized,double‐blind,phase III NAVIGATE trial

Psoriasis is a chronic disease causing red and scaling skin lesions. Current treatments, especially biologics, which are either given by injection or intravenous infusion (IV), are very effective in the treatment of moderate to severe plaque psoriasis. However, most patients look to achieve clear skin, so there is room for improvement. One approved biologic, ustekinumab, blocks two of the body's internal proteins, interleukin (IL)‐12 and IL‐23. Blocking these proteins prevents signals that cause inflammation in psoriasis. While ustekinumab is effective in many patients, most will not achieve complete skin clearance. Because recent scientific evidence shows that IL‐23 may be more important than IL‐12 in causing psoriasis, guselkumab, a new treatment that specifically targets IL‐23, but not IL‐12, has been developed and was recently approved in the U.S. to treat moderate to severe psoriasis. In the NAVIGATE trial, 871 patients with moderate‐to‐severe plaque psoriasis received ustekinumab and if, after 16 weeks, patients were not clear or almost clear, they were randomly assigned to either continue ustekinumab or start treatment with guselkumab until week 44. From week 16 until week 40, the average number of visits (maximum = 4) at which patients were clear or almost clear was significantly greater in patients treated with guselkumab (1.5) than with ustekinumab (0.7). In addition, at week 28, twice the proportion of patients on guselkumab (31.1%) were clear or almost clear than on ustekinumab (14.3%). Infections were the most commonly reported adverse event among patients on either guselkumab or ustekinumab. The authors conclude that for patients who do not achieve clear or almost clear skin after ustekinumab treatment, switching to guselkumab could be an effective treatment strategy and did not raise safety concerns.     

Guselkumab: A Review in Moderate to Severe Plaque Psoriasis

Guselkumab (Tremfya^®) is a human immunoglobulin G1 λ (IgG1λ) monoclonal antibody (mAb) that blocks the interleukin-23 (IL-23)-mediated signalling pathway and is the first in its class to be approved in adults with moderate to severe plaque psoriasis in several countries, including the USA and EU. In the VOYAGE trials, guselkumab was superior to placebo and to adalimumab at week 16 in terms of the proportion of patients achieving an Investigator Global Assessment (IGA) score of 0/1 and ≥ 90% improvement from baseline in Psoriasis Area and Severity index score (PASI 90 response), with benefits of guselkumab over adalimumab maintained at week 24. To date, the beneficial effects of guselkumab treatment in these trials were maintained for up to 2 years. Inadequate responders to ustekinumab who were then randomized to guselkumab in NAVIGATE showed better responses than those randomized to ustekinumab between weeks 28–40, with a significantly greater mean number of visits at which patients had IGA 0/1 and ≥ 2-grade improvement in IGA score, as well as higher proportions of patients achieving PASI 90 and PASI 100 at week 52. Treatment with guselkumab improved health-related quality of life (HR-QOL) and patient-reported outcomes in all trials and was generally well tolerated. Guselkumab, administered by subcutaneous injection, is a useful new option for patients with moderate to severe plaque psoriasis.     

Responses to ustekinumab in the anti‐TNF agent‐naïve vs. anti‐TNF agent‐exposed patients with psoriasis vulgaris

Background Approximately 20–30% of patients with psoriasis treated with anti‐tumour necrosis factor α (TNFα) agents will discontinue treatment within 2 years due to loss of efficacy or side‐effects. Switching to another anti‐TNFα agent produces clinical responses inferior to previously untreated patients. Ustekinumab binds to the p40 subunit of interleukin (IL)‐12 and IL‐23 and provides a mechanism of action independent of TNFα. Objective To investigate the efficacy of ustekinumab in a clinical practice setting and to compare treatment responses to ustekinumab in patients previously treated with TNFα inhibitors and anti‐TNFα‐naïve patients. Methods Patients receiving either ustekinumab (n = 71) or the subcutaneous TNFα inhibitors adalimumab or etanercept (n = 108) were identified through the registry of psoriasis patients in our Institutions. Efficacy effect outcome was a 75% improvement in the psoriasis area severity index (PASI75). Kaplan–Meier statistics evaluated the adherence to the treatments expressed as drug survival rate. Results PASI75 was achieved in 80% of the ustekinumab‐treated patients after a median time of 112 days. There was no difference in efficacy in anti‐TNFα‐naïve patients compared with anti‐TNFα unresponsive patients. Patients treated with ustekinumab showed a superior adherence to treatment in comparison with adalimumab and etanercept. Limitations Patients were non‐randomly assigned to treatment, which potentially may lead to biases. Observation time was short (1 year). Conclusion In clinical practice, the short‐term efficacy and patient adherence to ustekinumab are excellent and comparable to the data obtained in clinical trials. Lack of response to previous anti‐TNF treatment does not impair clinical response to ustekinumab.     

IL-17和IL-23拮抗剂治疗银屑病的研究进展

目前美国食品药品监督局（FDA）批准用于临床的IL-17抗体拮抗剂包括secukinumab、ixekizumab和brodalumab,三者治疗中度至重度斑块状银屑病皮损清除均优于对照组TNF-α拮抗剂,且安全性及耐受性均较好。三种IL-23拮抗剂risankizumab,guselkumab和tildrakizumab目前均在III期临床试验中,初步临床试验结果表明三种药物治疗银屑病较对照组TNF-α拮抗剂具有更快达到皮疹改善、更高皮疹清除率和注射次数更少的优势。本文就上述六种生物制剂治疗银屑病的研究进展进行了综述。     

Etanercept use for psoriasis in Taiwan: a case series study

Background The reported efficacy and safety of some biologic agents for psoriasis vary between Caucasians and Asians. Few reports of etanercept exist in psoriasis patients within the Asia‐Pacific region. Objectives The study aims to report our clinical experience of etanercept in the treatment of patients with moderate‐to‐severe psoriasis in Taiwan. Methods A retrospective analysis of 59 patients with moderate‐to‐severe psoriasis who received etanercept was conducted in a tertiary referral center. Results Etanercept therapy resulted in a reduction of mean Psoriasis Area and Severity Index (PASI) of 47% at week 12 and 61% at week 24. After 12 weeks of treatment, 48%, 26%, and 3.4% of the patients achieved at least PASI50, 75 and 90 response, respectively. At week 24, the proportion of patients achieving at least PASI50, 75 and 90 response was 59%, 37%, and 14%, respectively. Etanercept efficacy in achieving PASI75 improvement was, however, lower than that reported in previous pivotal placebo‐controlled trials. No cases of active tuberculosis, viral hepatitis or malignancies were observed during the observation period. Conclusion Our case series demonstrated the efficacy and safety of etanercept for the management of moderate‐to‐severe psoriasis in Taiwan.     

Efficacy and safety of adalimumab in patients with psoriasis previously treated with anti‐tumour necrosis factor agents: subanalysis of BELIEVE

Background Few large clinical studies have evaluated whether switching tumour necrosis factor antagonists (anti‐TNFs) is likely to improve psoriasis in patients with prior anti‐TNF treatment. Objective The aim of this subanalysis of the BELIEVE study was to assess the efficacy and safety of adalimumab for psoriasis in patients with and without previous anti‐TNF treatment. Methods The BELIEVE study enrolled patients with moderate to severe psoriasis and prior failure, intolerance or contraindication to ≥2 systemic therapies. In this 16‐week, double‐blind, randomized, controlled trial, patients received adalimumab (80 mg, week 0; 40 mg every other week, weeks 1–15) with either topical vehicle or topical calcipotriol/betamethasone dipropionate (C/B) applied once daily for 4 weeks, then as needed. The primary endpoint was ≥75% improvement from baseline in Psoriasis Area and Severity Index score (PASI 75) at week 16. This post hoc subanalysis evaluated the safety and efficacy of adalimumab, with and without topical therapy, in BELIEVE patients who had prior exposure to anti‐TNFs. Results Of 730 patients enrolled, 282 (38.6%) had prior anti‐TNFs and 448 (61.4%) were anti‐TNF‐naïve. Combining topical vehicle and topical C/B study populations, 61.7% of patients with prior anti‐TNFs achieved PASI 75 at week 16, compared with 71.7% of anti‐TNF‐naïve patients (P = 0.095). Adalimumab resulted in clinically meaningful improvement regardless of which prior anti‐TNF agent had been used, the number of prior anti‐TNFs tried, or reasons for discontinuation of prior anti‐TNF therapy. Adverse event incidences were similar between patients with and without prior anti‐TNF therapy. Conclusion Adalimumab was effective and well‐tolerated in patients with psoriasis previously treated with anti‐TNF therapy.     

Safety results from a pooled analysis of randomized,controlled phase II and III clinical trials and interim data from an open‐label extension trial of the interleukin‐12/23 monoclonal antibody,briakinumab, in moderate to severe psoriasis

Background Anti‐interleukin‐12/23 treatment (anti‐IL‐12/23) has recently demonstrated significant efficacy for moderate to severe psoriasis, yet potential safety signals warrant further investigation. Objectives Expand safety findings for the anti‐IL‐12/23, briakinumab, beyond individual phase II and III clinical trials. Methods Safety data pooled from five phase II and III clinical trials (parent studies) and an open‐label extension study (OLE), through 22 October 2010; patients with ≥1 dose of briakinumab in a parent study or the OLE are included. All parent study briakinumab treatment groups were combined with the OLE population, which received 100‐mg briakinumab every 4 weeks. Adverse events (AEs) were collected from the first dose of briakinumab, whether in a parent study or the OLE, through 45 days post‐last dose. Results Two thousand five hundred and twenty patients (4704 patient‐years drug exposure) received ≥1 dose of briakinumab during the interim period: 5.6% withdrew due to AEs. Serious infections occurred in 1.3% and malignancies in 2.6% (including 1.0% basal cell carcinoma, 0.8% squamous cell carcinoma). Twenty‐seven major adverse cardiovascular events (MACE) occurred, seven in one parent study and 20 in the OLE (incidence = 0.57 events/100 PY). Four cardiovascular risk factors were retrospectively found to be significant predictors for MACE during briakinumab exposure: history of cardiovascular disease, diabetes, body mass index (≥30) and baseline blood pressure (systolic ≥140 or diastolic ≥90). Conclusions Pooled briakinumab safety results from five parent studies and an OLE suggest increased rates of infections, malignancies and MACE, and that patients receiving anti‐IL‐12/23 treatment for moderate to severe psoriasis should be monitored for these potential safety signals.     

From randomized clinical trials to real life data. An Italian clinical experience with ixekizumab and its management

Interleukin(IL)‐17 inhibitors display higher efficacy than both TNFi and IL‐12/23i, which increased the goal psoriasis area severity index (PASI) from 75 to PASI 90 or even PASI 100. Ixekizumab, a recombinant, humanized IgG4 monoclonal antibody targeting IL‐17A displayed a high efficacy and safety in RCTs, namely UNCOVER‐2 and UNCOVER‐3. However, few studies examined real‐life data for these medications, and those which exist highlight discrepancies in efficacy and safety between RCTs and real‐life data, likely due to the heterogeneity of patients treated outside of trials. Thus, we performed a single center large prospective observational study (RLSD) that enrolled 47 psoriatic patients followed for 20 weeks and we compared the obtained data with the UNCOVER studies. At week 20 in RLSD versus UNCOVER‐3 both PASI‐90 and PASI‐100 results were similar, whilst at week 12, the RLSD cohort obtained higher PASI 90 (76 vs 69,3%) and PASI‐100 (55 vs 39%) than UNCOVER cohorts. Interestingly we also reported higher injection‐site related pain that disappeared after week 12. In conclusion, real‐life data together with RCTs contribute to enrich the information background available to dermatologists in daily practice.     

Efficacy and safety of secukinumab in Taiwanese patients with moderate to severe plaque psoriasis: Subanalysis from ERASURE phase III study

The efficacy and safety of secukinumab, a fully human anti‐interleukin‐17A monoclonal antibody, has been evaluated for moderate to severe plaque psoriasis in global trials which have included a low proportion of Asian subjects. We analyzed the efficacy and safety of secukinumab in Taiwanese patients in a phase III global clinical trial (ERASURE). Fifty‐one Taiwanese patients were randomized into s.c. placebo, 150 and 300 mg secukinumab treatment groups. The proportions of patients who achieved 75% or more improvement in Psoriasis Area and Severity Index (PASI‐75) at week 12 were 87.5% with 300 mg secukinumab, 70% with 150 mg secukinumab, 0% with placebo. Of the patients receiving 300 mg secukinumab, 68.8% achieved PASI‐90 at week 12. Analysis of overall patients receiving 300 mg secukinumab for 12 weeks showed that the proportion of PASI‐75 responders was less in patients with body mass index of 25 or more than less than 25. During the entire 52 weeks, the incidence of adverse events (AE) was consistent with the overall population in ERASURE. The most common AE (cases/per 100 patient‐year) during the entire treatment period were upper respiratory tract infection and pruritus. The duration of upper respiratory tract infection per 100 patient‐year was approximately 399 days in placebo, 1261 days in 150 mg secukinumab and 1805 days in 300 mg secukinumab. The safety and efficacy of secukinumab in Taiwanese patients was compatible with the global phase III study in the treatment of moderate to severe plaque psoriasis.     

Effectiveness and safety of secukinumab in 69 patients with moderate to severe plaque psoriasis: A retrospective multicenter study

Secukinumab (anti‐IL17A) is effective as treatment for moderate to severe plaque psoriasis, but real‐life data on effectiveness and safety lack. We aimed to present real‐life data of all Danish patients treated with secukinumab (n = 69). At baseline, before initiation of treatment with secukinumab 300 mg (47.8%) or off‐label treatment with secukinumab 150 mg (52.2%), the median PASI score was 7.1. A total of 66.7% (34/51) and 52.9% (27/51) of patients still on secukinumab at week 12 achieved a PASI (Psoriasis Area and Severity Index)‐50 and PASI‐75 of 66.7% and 52.9%, respectively. A total of 83.0% (44/53) and 60.4% (32/53) of the patients had a PASI‐score < 5 and PASI‐score < 2, respectively, after 12 weeks on treatment with secukinumab. A third of the patients had secukinumab discontinued due to limited clinical improvement or adverse events (n = 23) within a median of 92 days (interquartile range 51–212 days). Notably, the majority of the patients may represent a particularly difficult‐to‐treat group of patients, as 92.8% had been refractory to other biologic treatment. A total of 26.1% (n = 18) experienced adverse events. Secukinumab appears to be an effective treatment option with a favorable side effect profile in patients with plaque psoriasis who are refractory to or have side effects of traditional biologic drugs.     

The analysis of the therapeutic potential of ustekinumab in psoriasis vulgaris treatment

The molecular mechanism of ustekinumab action involves an interruption of signaling pathways activated by IL‐12/23. The aim of this paper was to evaluate the efficacy of the anti‐IL12/23 therapy in seven psoriatic patients by assessing changes in the values of psoriasis area and severity index (PASI), dermatology life quality index (DLQI), body surface area (BSA) indexes, and an analysis of changes in the mRNA expression profile of genes IL12A, IL12B, IL23A during three 40‐week long observation periods. The clinical (PASI, DLQI, BSA indexes) and molecular (RTqPCR for IL12A, IL12B, IL23A) analyses were performed on the day of ustekinumab therapy initiation, 4 weeks post first administration, and every 12 weeks thereafter. The statistically significant differences were observed only during Stage I for values of PASI (p = 0.0134), DLQI (p = 0.01299), BSA (p = 0.0355). During the subsequent stages, we observed lower values of PASI, BSA indexes, which suggests that the lesions are less intensified than at the moment of the therapy commencing. The relationship between the selected genes was observed: IL23A>IL12A>IL12B. In conclusion, the aforementioned clinical and molecular analysis suggests the efficacy of ustekinumab therapy in patients with psoriasis vulgaris can be analyzed with the PASI, BSA, DLQI indexes, and changes in the expression of selected genes. The analysis of IL12A, IL12B, IL23A expression may serve as a valuable supplementation for the therapeutic methods currently used to evaluate the degree of disease progression and treatment efficacy.     

Pharmacodynamic analysis of apremilast in Japanese patients with moderate to severe psoriasis: Results from a phase 2b randomized trial

We evaluated the pharmacodynamic effects of apremilast in 69 patients who were included in biomarker subanalyses of a phase 2b study that demonstrated the long‐term safety and efficacy of apremilast in Japanese adults with moderate to severe psoriasis. The association between cytokine levels and Psoriasis Area and Severity Index (PASI) improvement was evaluated using linear regression and Spearman’s rank correlation coefficient analysis. At baseline, median plasma levels of interleukin (IL)‐17A, IL‐17F and IL‐22 were elevated versus reference values for healthy individuals, whereas tumor necrosis factor‐α levels were close to normal. With apremilast 30 mg b.i.d., there were significant associations between percentage change in PASI score and percentage change in IL‐17A, IL‐17F and IL‐22 levels at week 16. Findings demonstrate that the efficacy of apremilast in psoriasis is associated with inhibition of key cytokines involved in the pathology of psoriasis.     

Biological therapy in genital psoriasis in women

Genital psoriasis (GenPs) is a frequent manifestation of psoriasis, causing distress, especially in women. We prospectively studied a population of 74 psoriatic women with severe and generalized psoriasis eligible to biologic therapy, to examine which biologic therapy is more effective on GenPs and to study possible associations between PASI severity and GenPs. Overall, 25/74 (34%) had GenPs: 6 received Ixekizumab, 7 Ustekinumab, 8 Adalimumab, 2 Secukinumab, 1 Etanercept, 1 Certolizumab. Therapies were administered based on PASI severity, independently from the presence of GenPs. Side effects, PASI score, sPGA‐G scale for GenPs were recorded at time 0 and after 6 month of therapy. The mean sPGA‐G scale value was 2.8 before treatment. After biologic therapy, all patients except one, improved of at least one point. Mostly, patients treated with anti‐IL17 (Secukinumab, Ixekizumab) and anti‐IL12/23 (Ustekinumab) improved. Mean PASI ranged from 10 to 16.3 before treatment. After 6 months of therapy, 4 anti‐TNFα patients, 6 anti‐IL17 and 1 anti‐IL12/23, reached PASI 90. At time 0, no correlation between PASI and sPGA‐G was visible (Pearson r = 0.10, p = .620). From our data, GenPs apparently responds favorably to IL17A inhibitors, but further studies, based on larger numbers of patients, are needed.     

Systematic review on rapidity of onset of action for interleukin-17 and interleukin-23 inhibitors for psoriasis

Several novel biologics are available or in development for moderate-to-severe plaque psoriasis. These drugs may differ in time until Psoriasis Area and Severity Index (PASI) response is obtained. In this systematic review, we examined the time to onset of action for interleukin (IL)-17 and IL-23 agents in the treatment of psoriasis. The primary objective was the weighted mean time needed for 25% and 50% of patients with psoriasis to achieve PASI90. The medical databases PubMed, Web of Science and EMBASE were searched using the following terms: psoriasis AND (ixekizumab OR secukinumab OR brodalumab OR risankizumab OR guselkumab OR tildrakizumab). A total of 27 studies were included for data extraction and qualitative synthesis, and 26 of these were quantitatively analysed. The shortest time to 25% and 50% of patients to achieved PASI90 were seen with brodalumab 210 mg every 2 weeks (Q2W; 3.5 weeks and 6.2 weeks, respectively) followed by ixekizumab 80 mg Q2W (4.1 and 7.4 weeks, respectively) and ixekizumab 80 mg Q4W (4.6 and 8.1 weeks, respectively) dosages. In conclusion, clinical trials yielded shorter time to onset of action in studies assessing approved dosing ranges of IL-17 inhibitors compared with studies assessing IL-23 inhibitors.     

Impact of ustekinumab on health‐related quality of life and sexual difficulties associated with psoriasis: results from two phase III clinical trials

Background Ustekinumab, a human anti‐interleukin‐12/23 monoclonal antibody, has been shown to effectively treat moderate‐to‐severe psoriasis which significantly affects health‐related quality of life (HRQoL), including patients’ sexual lives. Objectives The aim of this study was to determine if sexual difficulties associated with psoriasis are related to disease severity and whether sexual difficulties improve with skin disease during ustekinumab treatment. Methods  In phase III PHOENIX 1 and 2 trials, psoriasis patients were randomized to ustekinumab (n = 1334) at weeks 0 and 4 and q12 weeks thereafter or placebo (n = 662) at weeks 0 and 4 with crossover to ustekinumab at week 12. Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) were used to assess psoriasis severity and patient‐reported HRQoL respectively. Based on DLQI Question #9, impaired sexual function was defined as ‘very much’ or ‘a lot’ of sexual difficulties. Results At baseline, mean DLQI was 12.0, indicating a very large negative effect on patients’ lives. Impaired sexual function was reported by 22.6% (women = 27.1%; men = 20.8%) and was significantly associated with increased psoriasis severity. At week 12, ustekinumab‐treated patients had a greater mean improvement in DLQI (?9.13 vs. ?0.53 with placebo, P < 0.001) and the proportion of patients with impaired sexual function decreased from 22.4% to 2.7% compared with no change with placebo (P < 0.001). Patients with greater PASI improvement experienced a greater reduction of sexual difficulties due to psoriasis. A similar pattern of improved sexual function was observed at weeks 24–28 in placebo crossover patients. Conclusions Ustekinumab treatment is associated with significant improvement in HRQoL and sexual difficulties due to psoriasis.     

Guselkumab,a human interleukin‐23 monoclonal antibody in Japanese patients with generalized pustular psoriasis and erythrodermic psoriasis: Efficacy and safety analyses of a 52‐week,phase 3, multicenter,open‐label study

Generalized pustular psoriasis (GPP) and erythrodermic psoriasis (EP) are the rare and severe subtypes of psoriasis, which are often difficult to treat. The aim of this phase 3, open‐label study was to evaluate efficacy and safety of guselkumab, a human interleukin‐23 monoclonal antibody, in Japanese patients with GPP and EP. Guselkumab 50 mg was administrated to GPP (n = 10) and EP (n = 11) patients at weeks 0, 4 and thereafter every 8 weeks (q8w). Beginning at week 20, patients were escalated to 100 mg q8w if they met the dose escalation criteria. The primary end‐point was the proportion of patients achieving treatment success (Clinical Global Impression score of “very much improved”, “much improved” or “minimally improved”) at week 16. Safety evaluations included assessment of treatment‐emergent adverse events (TEAE) through week 52. At week 16, the proportions of GPP and EP patients achieving treatment success were 77.8% (7/9) and 90.9% (10/11), respectively. Furthermore, guselkumab treatment consistently showed improvement in responses of secondary end‐points such as Psoriasis Area and Severity Index, Investigator's Global Assessment, Japanese Dermatological Association severity index and improvement in body surface area involvement. Improvements in quality of life, as assessed by the Dermatology Life Quality Index, were also observed through week 52. The most commonly reported TEAE was nasopharyngitis (28.6%, 6/21). Safety findings were consistent with those observed previously in other studies. In conclusion, guselkumab treatment demonstrated efficacy and showed no safety concerns in Japanese patients with GPP and EP through week 52.