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Summary: Background: Risankizumab has demonstrated efficacy and safety in patients with moderate‐to‐severe plaque psoriasis in randomized clinical trials. Objectives: To evaluate safety data from risankizumab psoriasis phase I–III clinical trials. Methods: Short‐term safety (through week 16) was analysed using integrated data from five phase II and III clinical trials. Long‐term safety was evaluated using integrated data from 17 phase I–III completed and ongoing trials. Results: Short‐term safety analyses included 1306 patients receiving risankizumab 150 mg and 300 patients receiving placebo [402·2 and 92·0 patient‐years (PY) of exposure, respectively]. Long‐term analyses included 3072 risankizumab‐treated patients (exposure: 7927 PY). The median (excluding four outliers) treatment duration was 2·9 years (range 2 days to 5·9 years). Exposure‐adjusted adverse event rates did not increase with long‐term treatment (318 vs. 171 events per 100 PY for short‐ and long‐term analyses). With long‐term risankizumab treatment, rates of serious adverse events were 7·8 per 100 PY, serious infections 1·2 per 100 PY, nonmelanoma skin cancer (NMSC) 0·7 per 100 PY, malignant tumours excluding NMSC 0·5 per 100 PY, and adjudicated major adverse cardiovascular events 0·3 per 100 PY, with no important identified risks. Limitations include that the study inclusion and exclusion criteria varied and that three studies enrolled ≤ 50 patients. Conclusions: Risankizumab demonstrated a favourable safety profile over short‐ and long‐term treatment in patients with moderate‐to‐severe psoriasis. Whatis already known about this topic? In clinical trials of patients with moderate‐to‐severe plaque psoriasis, risankizumab, a selective interleukin‐23 inhibitor, was well tolerated and efficacious. Whatdoes this study add? In this comprehensive evaluation of risankizumab safety in patients with moderate‐to‐severe psoriasis, adverse event rates were comparable between risankizumab (n = 1306, 402 patient‐years) and placebo (n = 300, 92 patient‐years) in the short‐term (16‐week) analysis set, and were consistent with those in the long‐term analysis (n = 3072, 7927 patient‐years of risankizumab exposure).These findings are consistent with the known safety profile of risankizumab and support its long‐term use in moderate‐to‐severe psoriasis. Linked Comment: S. Mirali et al. Br J Dermatol 2022; 186:394–395. Plain language summary available online [ABSTRACT FROM AUTHOR]

Summary: Background: Certolizumab pegol (CZP) is an Fc‐free, PEGylated anti‐tumour necrosis factor biologic. Objectives: To report the 3‐year efficacy of CZP in plaque psoriasis, pooled from the CIMPASI‐1 (NCT02326298) and CIMPASI‐2 (NCT02326272) phase III trials. Methods: Adults with moderate‐to‐severe psoriasis for ≥ 6 months were randomized 2 : 2 : 1 to CZP 200 mg, CZP 400 mg or placebo, every 2 weeks (Q2W) for up to 48 weeks. Patients entering the open‐label period (weeks 48–144) from double‐blinded CZP initially received CZP 200 mg Q2W. Patients not achieving ≥ 50% improvement in Psoriasis Area and Severity Index (PASI 50) at week 16 entered an open‐label CZP 400 mg Q2W escape arm (weeks 16–144). Dose adjustments based on PASI response were permitted during open‐label treatment. Outcomes included PASI 75, PASI 90 and Physician's Global Assessment (PGA) 0/1 responder rates, based on a logistic regression model (missing data imputed using Markov Chain Monte Carlo methodology). Results: In total, 186 patients were randomized to CZP 200 mg Q2W and 175 to CZP 400 mg Q2W. At week 48, PASI 75/90 was achieved by 72·7%/51·3% of patients randomized to CZP 200 mg and 84·4%/62·7% randomized to CZP 400 mg. Patients entering the open‐label period at week 48, from blinded treatment, received CZP 200 mg Q2W. At week 144, PASI 75/90 was achieved by 70·6%/48·7% patients randomized to CZP 200 mg and 72·9%/42·7% randomized to CZP 400 mg. At week 16, 72 placebo‐randomized patients entered the CZP 400 mg Q2W escape arm; 75.7%/58.5% achieved PASI 75/90 at week 144. Conclusions: Both CZP 200 mg and 400 mg Q2W demonstrated sustained, durable efficacy, with numerically higher responses for some outcomes with 400 mg Q2W. What is already known about this topic? Certolizumab pegol is an Fc‐free, PEGylated, anti‐tumour necrosis factor biologic approved for adults with moderate‐to‐severe plaque psoriasis.Efficacy data from the first 48 weeks of phase III trials have shown significant improvements in the signs and symptoms of psoriasis with certolizumab pegol dosed at either 400 mg or 200 mg every 2 weeks.Numerically greater improvements were observed for patients treated with the higher dose. What does this study add? Plaque psoriasis is a chronic, systemic disease that requires long‐term management and sustained efficacy of therapies.Three‐year efficacy data pooled from the CIMPASI‐1 and CIMPASI‐2 phase III trials demonstrate a sustained and durable response to certolizumab pegol dosed at either 400 mg or 200 mg every 2 weeks.Additional long‐term clinical benefits may be obtained from the higher dose. Linked Comment: Johnson et al. Br J Dermatol 2021; 184:588–589. [ABSTRACT FROM AUTHOR]

Summary: Background: Patients with psoriasis value rapid and complete skin clearance. No head‐to‐head studies have focused on early responses to interleukin (IL)‐17 vs. IL‐23 inhibitors. Objectives: To compare early and complete skin clearance by the IL‐17A inhibitor ixekizumab vs. the IL‐23p19 inhibitor guselkumab. Methods: IXORA‐R, a 24‐week, randomized, double‐blinded study, enrolled adults with moderate‐to‐severe plaque psoriasis [static Physician's Global Assessment of Disease (sPGA) score of ≥ 3, Psoriasis Area and Severity Index (PASI) ≥ 12, and ≥ 10% body surface area]. Patients were randomized (1 : 1) to receive the approved dose of subcutaneous ixekizumab or guselkumab. Primary end point was 100% improvement in PASI (PASI 100) at week 12. Major secondary end points included other levels of improved PASI and sPGA at different time points. Comparisons were made using the Cochran–Mantel–Haenszel test with a multiple testing strategy. Nonresponder imputation was used for missing data. After the completion of the study, the final secondary end point (PASI 100 at 24 weeks) and safety data through week 24 will be reported. Results: In total, 1027 patients were randomized. The primary end point PASI 100 at week 12 was met [215/520 ixekizumab (41%); 126/507 guselkumab (25%); P < 0·001]. All major secondary end points measured up to week 12 were met, including PASI 50 at week 1 and PASI 75 at week 2. Serious adverse event frequency was 3% for each group; no new safety signals were identified. Conclusions: Ixekizumab was superior to guselkumab for rapidly improving signs and symptoms in patients with moderate‐to‐severe plaque psoriasis by week 12. Adverse events were similar to previous ixekizumab and guselkumab studies. Compared with the IL‐23 inhibitor guselkumab, ixekizumab can offer complete skin clearance more rapidly to patients with moderate‐to‐severe plaque psoriasis. What's already known about this topic? Patients with plaque psoriasis desire both high levels of clearance and rapid onset of treatment effects.Ixekizumab, a high‐affinity monoclonal antibody that selectively targets interleukin (IL)‐17A, has demonstrated greater and faster skin clearance than etanercept and ustekinumab, with consistent long‐term efficacy, safety and durability of response.Clinical trial data and systematic reviews have suggested that IL‐17 inhibitors can improve a patient's psoriasis more rapidly than IL‐23 inhibitors. What does this study add? The head‐to‐head study design directly compares the efficacy and speed of response of ixekizumab and the IL‐23 inhibitor guselkumab in moderate‐to‐severe plaque psoriasis.The primary end point was met, showing superiority of ixekizumab over guselkumab for achieving complete skin clearance at week 12.The safety profile of ixekizumab was consistent with previous studies.Ixekizumab can deliver patients complete skin clearance and improved quality of life more rapidly than guselkumab. Linked Comment:Veysey. Br J Dermatol 2020; 182:1321–1322. Plain language summary available online [ABSTRACT FROM AUTHOR]

Background: Psoriasis, a chronic disease usually requires long‐term disease management. Objective: This study evaluates the efficacy and safety of recommended ixekizumab (IXE) dose over 4 years (204 weeks) from UNCOVER‐3 study. Methods: UNCOVER‐3 was a randomised, double‐blind, multicenter, phase 3 study wherein patients with moderate‐to‐severe plaque psoriasis received placebo, IXE 80 mg every 2 weeks (Q2W), IXE 80 mg every 4 weeks (Q4W) (both IXE groups had 160 mg starting dose) or etanercept 50 mg twice weekly. At week 12, all patients switched to IXE Q4W dose for the long‐term extension (264 weeks). After week 60 and at investigator's discretion, patients could receive dose adjustment to IXE Q2W. The efficacy endpoints at week 204 were percentage of patients achieving PASI 75/90/100, sPGA score of 1 or 0, and those achieving PSSI = 0, NAPSI = 0 and PPASI 100. Efficacy data were summarised through 204 weeks using as‐observed, multiple imputation (MI) and modified non‐responder imputation (mNRI) methods. Results: The proportion of patients achieving PASI 75/90/100 at week 204 using mNRI method were 82.8%, 66.4% and 48.3%, respectively. Using as‐observed and MI methods, 98.2% and 94.8% patients achieved PASI 75, 87.8% and 73.3% achieved PASI 90, and 67.1% and 52.7% achieved PASI 100 response, respectively, at week 204. The response rates for sPGA (0, 1) were 88.7%, 76.2% and 68.5% and for sPGA (0) were 68.9%, 54.6% and 49.7% using as‐observed, MI and mNRI methods, respectively. Similar trends were observed with NAPSI = 0, PSSI = 0, PPASI 100 and itch NRS = 0. There were no new safety concerns through year 4. Conclusions: This study demonstrated sustained high‐efficacy response through 4 years of continuous treatment with ixekizumab in patients with moderate‐to‐severe plaque psoriasis. The safety profile remained consistent with prior findings, with no new or unexpected safety concerns. [ABSTRACT FROM AUTHOR]

Background Ongoing evaluation of biological agents in patients with moderate-to-severe psoriasis is needed to support their long-term use. Objective To evaluate long-term efficacy and safety of ustekinumab through 5 years in the PHOENIX 1 study. Methods Patients were randomized to placebo or ustekinumab (45 mg or 90 mg) at Weeks 0, 4 and every-12-weeks thereafter; placebo patients crossed-over to ustekinumab at Week 12. Clinical response through Week 244 was evaluated using the Psoriasis Area and Severity Index (PASI) in the Overall Population (i.e. patients receiving ≥1 dose of ustekinumab), Initial Responders (i.e. PASI 75 responders [Weeks 28/40] re-randomized at Week 40 to continue every-12-week maintenance) and Partial Responders (i.e.

Psoriasis is a chronic, debilitating skin condition that affects millions of people and is attributed to both genetic and environmental factors. Topical therapy is generally considered to be the first-line treatment of psoriasis. However, many patients do not respond to topical therapy or have disease so extensive that topical therapy is not practical. For these patients, systemic therapy is indicated. Presently, there are four available systemic treatments, psoralen with ultraviolet A (PUVA), methotrexate, oral retinoids (acitretin), and cyclosporin. Unfortunately, all of these treatments have significant potential adverse effects. PUVA may acutely cause nausea, pruritis and sunburn. More chronic and concerning is the development of PUVA lentigines, ocular complications and skin cancer. Non-melanoma skin cancer has been directly linked to PUVA; however, the association with melonoma is more elusive. Methotrexate use most notably carries the risk of hepatic fibrosis and cirrhosis, which is not always evident on liver function tests. Other more rare, but potentially life-threatening adverse effects include pancytopenia, lymphoproliferative disorders and acute pneumonitis. The addition of folic acid may help to reduce the risk of increasing liver enzymes and haematological toxicity seen in those taking methotrexate. Both methotrexate and oral retinoids are teratogenic and should never be used in pregnancy. Oral retinoids are probably the least effective available systemic medication for the treatment of plaque psoriasis. The effects are improved with the addition of other systemic therapies. Acitretin has replaced the formerly used etretinate primarily because of the significantly shorter half-life. The adverse effects are generally mild and reversible, making the drug fairly safe for long-term use. The most commonly seen adverse effects include elevated serum lipids, generalised xerosis and alopecia. Bony abnormalities, while somewhat controversial, have also been described and include diffuse idiopathic skeletal hyperostosis, skeletal calcifications and osteoporosis. Cyclosporin is the most recently approved systemic medication for plaque psoriasis. The nephrotoxicity associated with the use of cyclosporin can be minimised when used in lower doses and for a limited duration. Hypertension is usually mild and can be seen in up to about one-third of patients receiving long-term therapy. Cutaneous and internal malignancies have also been reported with cyclosporin and tend to be correlated with duration of treatment. In this review, we will examine the potential adverse effects with these US Food and Drug Administration-approved treatments in adults, with specific emphasis on the controversies that surround long-term therapy with these agents and their cumulative adverse effects. [ABSTRACT FROM AUTHOR]

Summary: 银屑病是一种皮肤病,会导致全身皮肤出现红色、鳞屑和瘙痒的斑块。 它影响着全球约 1.25 亿人。除了导致生活质量下降外,更广泛的银屑病往往会影响内在健康。过去几年开发的新药经常可以帮助银屑病患者实现完全清除皮损,并改善整体健康状况。 其中两种药物是 ixekizumab (IXE) 和 guselkumab (GUS)。然而,IXE 和 GUS 的工作方式不同,之前的一些研究表明,IXE 可能比 GUS 起效更快。 在这项研究中,来自美国和加拿大的研究人员对这些药物进行了直接对比测试,测量了开始用药后头 12 周的清除速度和皮肤完全清除率。 这项研究中的人接受了 IXE 或 GUS。12 周后,接受 IXE 治疗的人皮损完全清除者所占比例比接受 GUS 治疗的人高 16%(使用 IXE 的人为 41%,使用 GUS 的人为 25%)。 无论使用一周后皮肤清除率达 50% 的人数,还是使用两周后皮肤清除率达 75% 的人数,IXE 都比 GUS 多。与 GUS 相比,IXE 对瘙痒、皮肤疼痛和生活质量的改善也更快。IXE 和 GUS 出现严重副作用的患者数量相似。 总体而言,与使用 GUS 的患者相比,使用 IXE 的银屑病患者皮肤清除干净的速度更快,也更为迅速感觉好转。 本摘要涉及研究: 来自一项随机分配、双盲试验的 Ixekizumab 与 Guselkumab 治疗中度至重度斑块型银屑病患者的直接比较: 12 周疗效、安全性和应答速度 Linked Article: Blauvelt et al. Br J Dermatol 2020; 182:1348–1358 [ABSTRACT FROM AUTHOR]

Summary: Psoriasis is a skin disease that causes red, scaly and itchy patches of skin all over the body. It affects about 125 million people worldwide. As well as causing decreased quality of life, more widespread psoriasis often affects internal health. New drugs developed in the last few years often help people with psoriasis to achieve completely clear skin, and improve overall health. Two of these drugs are ixekizumab (IXE) and guselkumab (GUS). IXE and GUS work in different ways, however, and some prior research showed that IXE may work faster than GUS. In this study, researchers from the U.S.A. and Canada tested these drugs head‐to‐head, measuring speed of clearance and complete skin clearance rates over the first 12 weeks after starting drug. People in this study received either IXE or GUS. After 12 weeks, completely clear skin was achieved by 16% more people if they were treated with IXE compared to GUS (41% of people who took IXE versus 25% of people who took GUS). More people on IXE than GUS had 50% clearer skin after just one week and 75% clearer skin after two weeks. Itching, skin pain, and quality of life also improved faster with IXE compared to GUS. The number of patients with serious side effects was similar for IXE and GUS. Overall, people with psoriasis who take IXE may get clear skin faster and feel better more quickly than people who take GUS. This is a summary of the study: A head‐to‐head comparison of ixekizumab vs. guselkumab in patients with moderate‐to‐severe plaque psoriasis: 12‐week efficacy, safety and speed of response from a randomized, double‐blinded trial Linked Article: Blauvelt et al. Br J Dermatol 2020; 182:1348–1358 [ABSTRACT FROM AUTHOR]

The article focuses on a study which examined the efficacy of ixekizumab in treating patients with psoriasis vulgaris. Clinical information on psoriasis vulgaris is provided, along with a description of the medical history of the study subjects. Study authors found increased improvement in patients who received ixekizumab in terms of health-related quality of life and pruritus symptom relief.