New generation biologics, including interleukin (IL)-17 and IL-23 inhibitors, have delivered higher rates of skin clearance than older treatments in head-to-head studies. However, studies comparing ...these new biologics directly to one another are limited.
To compare the short-term efficacy of available (or imminently available) biologic and non-biologic systemic therapies for treating patients with moderate-to-severe plaque psoriasis.
A systematic review was undertaken to identify randomised controlled trials evaluating biologic treatments, apremilast and dimethyl fumarate. MEDLINE, MEDLINE In-Process, Embase and the Cochrane Library were searched from the 1st January 2000 to 22nd November 2018. A Bayesian network meta-analysis (NMA) using a random-effects multinomial likelihood model with probit link and meta-regression to adjust for cross-trial variation in placebo responses compared the efficacy of interventions at inducing different levels of Psoriasis Area and Severity Index (PASI) response during the induction period. A range of sensitivity analyses was undertaken.
Seventy-seven trials (34,816 patients) were included in the NMA. The base-case analysis showed that all active treatments were superior to placebo. IL-17 inhibitors, guselkumab and risankizumab were found to be more efficacious than tildrakizumab, ustekinumab, all TNF inhibitors and non-biologic systemic treatments at inducing all levels of PASI response. In addition, brodalumab, ixekizumab and risankizumab were significantly more efficacious than secukinumab; no significant difference was found in the comparison with guselkumab. The greatest benefit of brodalumab, ixekizumab, guselkumab, and risankizumab was seen for PASI 90 and PASI 100 response. Results were consistent across all analyses.
In the NMA brodalumab, ixekizumab, risankizumab and guselkumab showed the highest levels of short-term efficacy. There were differences in efficacy between treatments within the same class. Longer-term analyses are needed to understand differences between these drugs beyond induction in what is a life-long condition.
: Ixekizumab (an IL-17A antagonist) is a biologic therapeutic licensed for use in moderate-to-severe plaque psoriasis and psoriatic arthritis. IL-17 antagonists (also including Secukinumab and ...Brodalumab) represent a new generation of biologic therapy with rapid and high response rates, quickly becoming a crucial part of the psoriasis treatment armamentarium.
: In this review, we describe how IL-17A antagonists disrupt inflammatory cascades in psoriasis and summarize results from clinical trials examining the safety and efficacy of ixekizumab against placebo and comparators.
: Ixekizumab induces a 75% reduction in psoriasis area severity index (PASI 75) in 89% of patients after 12 weeks and after 1 year, PASI 75 is maintained in 80% of patients. Ixekizumab is superior to both etanercept and ustekinumab, however, further comparator trials are needed to determine superiority between newer agents. Network meta-analysis suggests that ixekizumab is one of the most rapid and efficacious agents for treating psoriasis, but ideally more long-term real-world data are needed to determine the persistence of response. Candida may be commonly encountered during treatment and IL-17 agents should be avoided in patients with inflammatory bowel disease. Overall, ixekizumab represents an efficacious and well-studied therapeutic that can offer biologic-naïve and bio-failure patients durable disease control.
There is an unmet need for a treatment for psoriasis that results in complete skin clearance with a reliably quick response. Bimekizumab is a monoclonal IgG1 antibody that selectively inhibits ...interleukin (IL)-17F in addition to IL-17A. We aimed to compare the efficacy and safety of bimekizumab with placebo and ustekinumab in patients with moderate to severe plaque psoriasis over 52 weeks.
BE VIVID was a multicentre, randomised, double-blind, active comparator and placebo controlled phase 3 trial done across 105 sites (clinics, hospitals, research units, and private practices) in 11 countries in Asia, Australia, Europe, and North America. Adults aged 18 years or older with moderate to severe plaque psoriasis (Psoriasis Area and Severity Index PASI score ≥12, ≥10% body surface area affected by psoriasis, and Investigator's Global Assessment IGA score ≥3 on a five point scale) were included. Randomisation was stratified by geographical region and previous exposure to biologics; patients, investigators, and sponsors were masked to treatment assignment. Patients were randomly assigned (4:2:1) using an interactive response technology to bimekizumab 320 mg every 4 weeks, ustekinumab 45 mg or 90 mg (baseline weight-dependent dosing) at weeks 0 and 4, then every 12 weeks, or placebo every 4 weeks. At week 16, patients receiving placebo switched to bimekizumab 320 mg every 4 weeks. All study treatments were administered as two subcutaneous injections. Coprimary endpoints were the proportion of patients with 90% improvement in the PASI (PASI90) and the proportion of patients with an IGA response of clear or almost clear (score 0 or 1) at week 16 (non-responder imputation). Efficacy analyses included the intention-to-treat population; safety analysis included patients who received at least one dose of study treatment. This trial was registered at ClinicalTrials.gov, NCT03370133 (completed).
Between Dec 6, 2017, and Dec 13, 2019, 735 patients were screened and 567 were enrolled and randomly assigned (bimekizumab 320 mg every 4 weeks n=321, ustekinumab 45 mg or 90 mg every 12 weeks n=163, placebo n=83). At week 16, 273 (85%) of 321 patients in the bimekizumab group had PASI90 versus 81 (50%) of 163 in the ustekinumab group (risk difference 35 95% CI 27–43; p<0·0001) and four (5%) of 83 in the placebo group (risk difference 80 74–86; p<0·0001). At week 16, 270 (84%) patients in the bimekizumab group had an IGA response versus 87 (53%) in the ustekinumab group (risk difference 30 95% CI 22–39; p<0·0001) and four (5%) in the placebo group (risk difference 79 73–85; p<0·0001). Over 52 weeks, serious treatment-emergent adverse events were reported in 24 (6%) of 395 patients in the bimekizumab group (including those who switched from placebo at week 16) and 13 (8%) of 163 in the ustekinumab group.
Bimekizumab was more efficacious than ustekinumab and placebo in the treatment of moderate to severe plaque psoriasis. The bimekizumab safety profile was consistent with that observed in previous studies.
UCB Pharma.
To compare accuracy, precision, and reproducibility of four commonly used myocardial T1 mapping sequences: modified Look-Locker inversion recovery (MOLLI), shortened MOLLI (ShMOLLI), saturation ...recovery single-shot acquisition (SASHA), and saturation pulse prepared heart rate independent inversion recovery (SAPPHIRE).
This HIPAA-compliant study was approved by the institutional review board. All subjects provided written informed consent. Accuracy, precision, and reproducibility of the four T1 mapping sequences were first compared in phantom experiments. In vivo analysis was performed in seven healthy subjects (mean age ± standard deviation, 38 years ± 19; four men, three women) who were imaged twice on two separate days. In vivo reproducibility of native T1 mapping and extracellular volume (ECV) were measured. Differences between the sequences were assessed by using Kruskal-Wallis and Wilcoxon rank sum tests (phantom data) and mixed-effect models (in vivo data).
T1 mapping accuracy in phantoms was lower with ShMOLLI (62 msec) and MOLLI (44 msec) than with SASHA (13 msec; P < .05) and SAPPHIRE (12 msec; P < .05). MOLLI had similar precision to ShMOLLI (4.0 msec vs 5.6 msec; P = .07) but higher precision than SAPPHIRE (6.8 msec; P = .002) and SASHA (8.7 msec; P < .001). All sequences had similar reproducibility in phantoms (P = .1). The four sequences had similar in vivo reproducibility for native T1 mapping (∼25-50 msec; P > .05) and ECV quantification (∼0.01-0.02; P > .05).
SASHA and SAPPHIRE yield higher accuracy, lower precision, and similar reproducibility compared with MOLLI and ShMOLLI for T1 measurement. Different sequences yield different ECV values; however, all sequences have similar reproducibility for ECV quantification.
Psoriasis is a common inflammatory skin condition affecting approximately 2–3% of people worldwide. Methotrexate (MTX) is a cheap and effective drug that is often recommended as the first-choice ...systemic agent for psoriasis. Around 40–50% of patients achieve a good response; however, mechanisms of nonresponse are poorly understood. It is not known whether biochemical MTX adherence in patients with psoriasis is suboptimal and requires intervention. Our aim was to audit biochemical MTX adherence using a sensitive liquid chromatography–tandem mass spectrometry in patients prescribed oral MTX for the treatment of psoriasis at our tertiary dermatology centre. Ethical approval for this audit was not required as confirmed by the Health Research Authority.
Effective, well-tolerated oral psoriasis treatments are needed.
To compare the efficacy and safety of deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, versus placebo and ...apremilast in adults with moderate to severe plaque psoriasis.
Participants were randomized 2:1:1 to deucravacitinib 6 mg every day (n = 332), placebo (n = 166), or apremilast 30 mg twice a day (n = 168) in the 52-week, double-blinded, phase 3 POETYK PSO-1 trial (NCT03624127). Coprimary end points included response rates for ≥75% reduction from baseline in Psoriasis Area and Severity Index (PASI 75) and static Physician's Global Assessment score of 0 or 1 (sPGA 0/1) with deucravacitinib versus placebo at week 16.
At week 16, response rates were significantly higher with deucravacitinib versus placebo or apremilast for PASI 75 (194 58.4% vs 21 12.7% vs 59 35.1%; P < .0001) and sPGA 0/1 (178 53.6% vs 12 7.2% vs 54 32.1%; P < .0001). Efficacy improved beyond week 16 and was maintained through week 52. Adverse event rates with deucravacitinib were similar to those with placebo and apremilast.
One-year duration, limited racial diversity.
Deucravacitinib was superior to placebo and apremilast across multiple efficacy end points and was well tolerated in moderate to severe plaque psoriasis.
Dual neutralisation of interleukin 17A (IL17A) and interleukin 17F (IL17F) is a potential novel therapeutic approach in psoriatic arthritis. We assessed bimekizumab, a monoclonal antibody that ...selectively neutralises IL17A and IL17F, in patients with active psoriatic arthritis.
BE ACTIVE was a randomised, double-blind, placebo-controlled, dose-ranging phase 2b study done at 41 sites in the Czech Republic, Germany, Hungary, Poland, Russia, and the USA. Eligible patients aged 18 years or older with active adult-onset psoriatic arthritis and symptoms for at least 6 months were randomly assigned (1:1:1:1:1) to placebo, 16 mg bimekizumab, 160 mg bimekizumab, 160 mg bimekizumab with a one-off 320 mg loading dose, or 320 mg bimekizumab, which were administered as subcutaneous injections every 4 weeks for 12 weeks. After 12 weeks, patients assigned to the placebo and 16 mg bimekizumab groups were randomly reassigned (1:1) to either 160 mg or 320 mg bimekizumab, and all other patients remained on their originally assigned initial dose up to 48 weeks. Both participants and researchers were blinded to treatment allocation in the first 12 weeks, and blinded to the dose of bimekizumab thereafter. The primary endpoint was the proportion of patients with at least 50% improvement in the American College of Rheumatology response criteria at week 12, which was assessed in all patients who received at least one dose of study treatment and had a valid measurement of the primary efficacy endpoint at baseline. The trial, including all follow-up, has been completed. This trial is registered with ClinicalTrials.gov, NCT02969525.
Between Oct 27, 2016, and July 16, 2018, 308 patients were screened, and 206 were randomly assigned: 42 to the placebo group, and 41 each to the four bimekizumab groups. At 12 weeks, compared with the placebo group, significantly more patients in the 16 mg bimekizumab (odds ratio OR 4·2 95% CI 1·1–15·2; p=0·032), 160 mg bimekizumab (8·1 2·3–28·7; p=0·0012), and 160 mg (loading dose) bimekizumab (9·7 2·7–34·3; p=0·0004) groups achieved an ACR50 response. At 12 weeks, 24 (57%) of 42 patients in the placebo group and 68 (41%) of the 164 patients in the bimekizumab groups reported treatment-emergent adverse events. Most of these adverse events were mild or moderate. Serious treatment-emergent adverse events occurred in nine patients, eight of whom were receiving bimekizumab. No deaths or cases of inflammatory bowel disease were reported.
Bimekizumab doses of 16 mg and 160 mg (with or without a 320 mg loading dose) were associated with significant improvements in ACR50 compared with placebo, with an acceptable safety profile. Our results support phase 3 investigation of bimekizumab as a treatment for psoriatic arthritis.
UCB Pharma.
Bimekizumab is a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17A and IL-17F. We assessed the efficacy and safety of bimekizumab in patients with active psoriatic arthritis who ...were naive to biologic disease-modifying antirheumatic drugs (DMARDs).
BE OPTIMAL was a 52-week, phase 3, multicentre, randomised, double-blind, placebo-controlled, active reference (adalimumab) trial done at 135 sites (hospitals, clinics, doctors' offices, and research centres) in 14 countries. Eligible patients were 18 years or older with a documented diagnosis of adult-onset psoriatic arthritis that met the Classification Criteria for Psoriatic Arthritis for at least 6 months before screening. Participants were randomly assigned with an interactive-voice and web-response system on the basis of a predetermined randomisation schedule (3:2:1, stratified by region and bone erosion number at baseline) to bimekizumab 160 mg every 4 weeks, placebo every 2 weeks, or the reference group (adalimumab 40 mg every 2 weeks), all administered subcutaneously. At week 16, patients randomly assigned to placebo switched to bimekizumab 160 mg every 4 weeks. The primary endpoint was the proportion of patients reaching 50% or greater improvement in American College of Rheumatology criteria (ACR50) at week 16 (non-responder imputation). Efficacy analyses included all patients who were randomly assigned (intention-to-treat population); the safety analysis set comprised patients who received one or more doses of treatment. Data are presented to week 24 (preplanned analysis). This trial is registered at ClinicalTrials.gov, NCT03895203.
Between April 3, 2019, and Oct 25, 2021, 1163 patients were screened and 852 were randomly assigned to bimekizumab (n=431), placebo (n=281), and reference (adalimumab; n=140) groups. At week 16, significantly more patients receiving bimekizumab (189 44% of 431) reached ACR50 response versus placebo (28 10% of 281; odds ratio 7·1 95% CI 4·6–10·9, p<0·0001; adalimumab 64 46% of 140). All secondary hierarchical endpoints were met. Treatment-emergent adverse events up to week 16 were reported in 258 60% of 431 patients receiving bimekizumab, 139 49% of 281 patients receiving placebo, and 83 59% of 140 patients receiving adalimumab. No deaths occurred.
Bimekizumab treatment had superior improvements in joint, skin, and radiographic efficacy outcomes at week 16 compared with placebo in patients with psoriatic arthritis who were naive to biologic DMARDs. The safety profile of bimekizumab, including the occurrence of fungal infections, was consistent with previous phase 3 studies in patients with plaque psoriasis, and with IL-17A inhibitors.
UCB Pharma.
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