A few weeks, a friend of mine directed me to a paper in the Blue Journal, the Journal of the American Academy of Dermatology, and congratulated me: I was ranked in the paper among the first 25 top ...authors in Dermatology by career-long total citations 1996-2019 ...
Background
Psoriasis is an immune‐mediated disease for which some people have a genetic predisposition. The condition manifests in inflammatory effects on either the skin or joints, or both, and it ...has a major impact on quality of life. Although there is currently no cure for psoriasis, various treatment strategies allow sustained control of disease signs and symptoms. Several randomised controlled trials (RCTs) have compared the efficacy of the different systemic treatments in psoriasis against placebo. However, the relative benefit of these treatments remains unclear due to the limited number of trials comparing them directly head‐to‐head, which is why we chose to conduct a network meta‐analysis.
Objectives
To compare the efficacy and safety of non‐biological systemic agents, small molecules, and biologics for people with moderate‐to‐severe psoriasis using a network meta‐analysis, and to provide a ranking of these treatments according to their efficacy and safety.
Search methods
For this living systematic review we updated our searches of the following databases monthly to September 2020: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase. We searched two trials registers to the same date. We checked the reference lists of included studies and relevant systematic reviews for further references to eligible RCTs.
Selection criteria
Randomised controlled trials (RCTs) of systemic treatments in adults (over 18 years of age) with moderate‐to‐severe plaque psoriasis or psoriatic arthritis whose skin had been clinically diagnosed with moderate‐to‐severe psoriasis, at any stage of treatment, in comparison to placebo or another active agent. The primary outcomes of this review were: the proportion of participants who achieved clear or almost clear skin, that is, at least Psoriasis Area and Severity Index (PASI) 90 at induction phase (from 8 to 24 weeks after the randomisation), and the proportion of participants with serious adverse events (SAEs) at induction phase. We did not evaluate differences in specific adverse events.
Data collection and analysis
Several groups of two review authors independently undertook study selection, data extraction, 'Risk of bias' assessment, and analyses. We synthesised the data using pair‐wise and network meta‐analysis (NMA) to compare the treatments of interest and rank them according to their effectiveness (as measured by the PASI 90 score) and acceptability (the inverse of serious adverse events).
We assessed the certainty of the body of evidence from the NMA for the two primary outcomes and all comparisons, according to CINeMA, as either very low, low, moderate, or high. We contacted study authors when data were unclear or missing.
We used the surface under the cumulative ranking curve (SUCRA) to infer on treatment hierarchy: 0% (treatment is the worst for effectiveness or safety) to 100% (treatment is the best for effectiveness or safety).
Main results
We included 158 studies (18 new studies for the update) in our review (57,831 randomised participants, 67.2% men, mainly recruited from hospitals). The overall average age was 45 years; the overall mean PASI score at baseline was 20 (range: 9.5 to 39). Most of these studies were placebo‐controlled (58%), 30% were head‐to‐head studies, and 11% were multi‐armed studies with both an active comparator and a placebo. We have assessed a total of 20 treatments. In all, 133 trials were multicentric (two to 231 centres). All but two of the outcomes included in this review were limited to the induction phase (assessment from 8 to 24 weeks after randomisation). We assessed many studies (53/158) as being at high risk of bias; 25 were at an unclear risk, and 80 at low risk. Most studies (123/158) declared funding by a pharmaceutical company, and 22 studies did not report their source of funding.
Network meta‐analysis at class level showed that all of the interventions (non‐biological systemic agents, small molecules, and biological treatments) were significantly more effective than placebo in reaching PASI 90.
At class level, in reaching PASI 90, the biologic treatments anti‐IL17, anti‐IL12/23, anti‐IL23, and anti‐TNF alpha were significantly more effective than the small molecules and the non‐biological systemic agents.
At drug level, infliximab, ixekizumab, secukinumab, brodalumab, risankizumab and guselkumab were significantly more effective in reaching PASI 90 than ustekinumab and three anti‐TNF alpha agents: adalimumab, certolizumab, and etanercept. Ustekinumab and adalimumab were significantly more effective in reaching PASI 90 than etanercept; ustekinumab was more effective than certolizumab, and the clinical effectiveness of ustekinumab and adalimumab was similar. There was no significant difference between tofacitinib or apremilast and three non‐biological drugs: fumaric acid esters (FAEs), ciclosporin and methotrexate.
Network meta‐analysis also showed that infliximab, ixekizumab, risankizumab, bimekizumab, secukinumab, guselkumab, and brodalumab outperformed other drugs when compared to placebo in reaching PASI 90. The clinical effectiveness of these drugs was similar, except for ixekizumab which had a better chance of reaching PASI 90 compared with secukinumab, guselkumab and brodalumab. The clinical effectiveness of these seven drugs was: infliximab (versus placebo): risk ratio (RR) 50.29, 95% confidence interval (CI) 20.96 to 120.67, SUCRA = 93.6; high‐certainty evidence; ixekizumab (versus placebo): RR 32.48, 95% CI 27.13 to 38.87; SUCRA = 90.5; high‐certainty evidence; risankizumab (versus placebo): RR 28.76, 95% CI 23.96 to 34.54; SUCRA = 84.6; high‐certainty evidence; bimekizumab (versus placebo): RR 58.64, 95% CI 3.72 to 923.86; SUCRA = 81.4; high‐certainty evidence; secukinumab (versus placebo): RR 25.79, 95% CI 21.61 to 30.78; SUCRA = 76.2; high‐certainty evidence; guselkumab (versus placebo): RR 25.52, 95% CI 21.25 to 30.64; SUCRA = 75; high‐certainty evidence; and brodalumab (versus placebo): RR 23.55, 95% CI 19.48 to 28.48; SUCRA = 68.4; moderate‐certainty evidence. Conservative interpretation is warranted for the results for bimekizumab (as well as mirikizumab, tyrosine kinase 2 inhibitor, acitretin, ciclosporin, fumaric acid esters, and methotrexate), as these drugs, in the NMA, have been evaluated in few trials.
We found no significant difference between any of the interventions and the placebo for the risk of SAEs. Nevertheless, the SAE analyses were based on a very low number of events with low to moderate certainty for all the comparisons. Thus, the results have to be viewed with caution and we cannot be sure of the ranking.
For other efficacy outcomes (PASI 75 and Physician Global Assessment (PGA) 0/1) the results were similar to the results for PASI 90.
Information on quality of life was often poorly reported and was absent for several of the interventions.
Authors' conclusions
Our review shows that compared to placebo, the biologics infliximab, ixekizumab, risankizumab, bimekizumab, secukinumab, guselkumab and brodalumab were the most effective treatments for achieving PASI 90 in people with moderate‐to‐severe psoriasis on the basis of moderate‐ to high‐certainty evidence. This NMA evidence is limited to induction therapy (outcomes were measured from 8 to 24 weeks after randomisation) and is not sufficient for evaluation of longer‐term outcomes in this chronic disease. Moreover, we found low numbers of studies for some of the interventions, and the young age (mean age of 45 years) and high level of disease severity (PASI 20 at baseline) may not be typical of patients seen in daily clinical practice.
Another major concern is that short‐term trials provide scanty and sometimes poorly‐reported safety data and thus do not provide useful evidence to create a reliable risk profile of treatments. We found no significant difference in the assessed interventions and placebo in terms of SAEs, and the evidence for all the interventions was of low to moderate quality. In order to provide long‐term information on the safety of the treatments included in this review, it will also be necessary to evaluate non‐randomised studies and postmarketing reports released from regulatory agencies.
In terms of future research, randomised trials directly comparing active agents are necessary once high‐quality evidence of benefit against placebo is established, including head‐to‐head trials amongst and between non‐biological systemic agents and small molecules, and between biological agents (anti‐IL17 versus anti‐IL23, anti‐IL23 versus anti‐IL12/23, anti‐TNF alpha versus anti‐IL12/23). Future trials should also undertake systematic subgroup analyses (e.g. assessing biological‐naïve participants, baseline psoriasis severity, presence of psoriatic arthritis, etc.). Finally, outcome measure harmonisation is needed in psoriasis trials, and researchers should look at the medium‐ and long‐term benefit and safety of the interventions and the comparative safety of different agents.
Editorial note: This is a living systematic review. Living systematic reviews offer a new approach to review updating, in which the review is continually updated, incorporating relevant new evidence as it becomes available. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.
Abstract Instruments to measure and to monitor the severity of psoriasis over time are needed for research and for optimal patient care. Scoring psoriasis has moved from an earlier time when clinical ...categories were adopted without concern about their reliability; for example, from clearance to more recent semi-quantitative scores, such as the Psoriasis Area and Severity Index (PASI), that carry the allure of being objective and quantitative “hard” data but actually translate a subjective judgement into a number. The PASI score has never been standardized, and data on interrater and intrarater reliability are limited. Better clinimetrics of disease severity are needed. The next generation of instruments should reflect the major concern of patients and treating physicians relative to safe and effective long-term disease control for a lifelong condition.
Abstract Cancer is one of the several comorbidities that have been linked with psoriasis. Not surprisingly, tumors associated with well-documented risk factors for the dermatosis, such as smoking and ...obesity, have been found with increased incidence in psoriatic patients. They include lung, kidney, and colon cancers. For unknown reasons, the risk of lymphoma is also increased in psoriatic patients. Despite several difficulties with documenting risks, some systemic treatments for psoriasis have been linked with an increased risk of selected cancers. The best-documented association is nonmelanoma skin cancer with psoralen plus ultraviolet A therapy and cyclosporin. More recently, an increased risk of cancer has been a concern with newly introduced biologic agents. The documentation of such a purported increased risk requires long-term follow-up of treated patients.
Retroareolar cysts (RCs) are a benign self‐resolving condition primarily affecting pubertal individuals. However, their presentation as asymptomatic bluish areolar lumps remains underreported in the ...literature, with only six cases previously documented. This lack of awareness may lead to the oversight of RCs during diagnosis. To address this, we conducted a comprehensive literature review using PUBMED, and we further added three more cases. The mean time for clinical resolution was found to be 2.3 years. In light of these findings, we proposed a diagnostic and management algorithm to guide clinicians in their approach to RCs in pediatric patients. The algorithm involves thorough clinical examination, medical history assessment, and echographic investigation with color Doppler analysis. Regular follow‐up visits are recommended until resolution of the lesions. Notably, due to the consistently favorable outcome of RCs, aggressive diagnostic interventions can be avoided, providing reassurance to patients and their families. It is crucial for paediatricians to stay updated on this underreported condition to ensure timely recognition and appropriate management. Dermatologists should be the first specialists to be consulted in cases of suspected RCs. Increasing awareness among healthcare professionals will contribute to improved diagnosis and management of this benign condition. In conclusion, RCs are a benign self‐resolving condition commonly observed during puberty. Their presentation as asymptomatic bluish areolar lumps may often be overlooked. Through this study, we highlighted the importance of early recognition, proposed a diagnostic and management algorithm, and emphasized the favorable prognosis of RCs, which allows for a conservative approach to their management.
Background Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare severe cutaneous adverse reactions. Objectives We sought to update knowledge on the causes of SJS or TEN with a ...focus on the rate of allopurinol-associated cases and to identify risk factors for allopurinol-associated SJS or TEN. Methods We conducted a multinational case-control study. Results In all, 379 patients with severe cutaneous adverse reactions validated as SJS or TEN and 1505 matched hospitalized control subjects were enrolled. Allopurinol was the drug most frequently associated with SJS or TEN, with 66 exposed patients (17.4%) and 28 exposed control subjects (1.9%) (adjusted odds ratio = 18, 95% confidence interval: 11-32). Allopurinol use was greater than in a previous case-control European study. Daily doses equal to or greater than 200 mg were associated with a higher risk (adjusted odds ratio = 36, 95% confidence interval: 17-76) than lower doses (adjusted odds ratio = 3.0, 95% confidence interval: 1.1-8.4). The risk was restricted to short-term use (≤8 weeks). The use of comedications did not increase the risk. Limitations Nonsystematic recording of the indications for allopurinol use was a limitation. Conclusions Results of this multinational study (EuroSCAR) revealed that allopurinol is the drug most commonly associated with SJS or TEN. The incidence of allopurinol-associated SJS or TEN has increased possibly because of increased use and dosages of this drug.
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