Efficacy and tolerability of biologic and nonbiologic systemic treatments for moderate-to-severe psoriasis: meta-analysis of randomized controlled trials

Background The comparative efficacy and tolerability of conventional and biologic treatments for moderate‐to‐severe plaque psoriasis are unknown. Objectives To perform a systematic review and meta‐analysis of randomized controlled trials (RCTs) reporting efficacy of systemic treatments approved for moderate‐to‐severe psoriasis by means of the Psoriasis Area and Severity Index (PASI). Methods We identified relevant articles by systematic electronic searches (Cochrane Library, Medline, Embase, Scopus). Efficacy was defined as proportion of participants with ≥ 75% decrease in PASI (PASI‐75) at primary efficacy measurement (week 8–16). PASI‐75 response rates of double‐blind placebo‐controlled trials were summarized as risk differences (RDs) and pooled using random effects models. Tolerability was assessed from rates of withdrawals and adverse events. Results Twenty‐four RCTs totalling 9384 patients were analysed qualitatively. Sixteen double‐blind placebo‐controlled trials were eligible for meta‐analysis. Infliximab was significantly superior to all other interventions [RD 77%, 95% confidence interval (CI) 72–81%]. Adalimumab (RD 64%, 95% CI 61–68%) was superior to ciclosporin (RD 33%, 95% CI 13–52%), efalizumab (RD 24%, 95% CI 19–30%), etanercept 50 mg twice weekly (RD 44%, 95% CI 40–48%) and etanercept 25 mg twice weekly (RD 30%, 95% CI 25–35%). Efalizumab was significantly less efficacious than fumaric acid esters (RD 48%, 95% CI 32–64%). Rates of withdrawals due to adverse events were highest for methotrexate and fumaric acid esters. Conclusions The efficacy of systemic agents approved for moderate‐to‐severe psoriasis differs considerably both within and between biologics and nonbiologics. Infliximab is most efficacious, followed by adalimumab. Patients receiving infliximab have an excess chance of 77% over placebo to achieve PASI‐75 response. Published evidence questions regulatory guidelines that recommend biologics as second‐line therapy for moderate‐to‐severe plaque psoriasis.     

Efficacy of systemic therapies for moderate‐to‐severe psoriasis: a systematic review and meta‐analysis of long‐term treatment

Background Despite the chronicity of psoriasis, most systematic reviews focus on short‐term treatment. Methods The systematic search strategy and results from the German Psoriasis Guidelines were adapted. To update the data a literature search in Medline, Embase and the Cochrane Library was conducted. The proportion of participants achieving ≥75% decrease in Psoriasis Area and Severity Index (PASI) as well as Dermatology Life Quality Index (DLQI) reduction at different time points were assessed. Trials were summarized with respect to time periods and study designs. Suitable trials were included in a meta‐analysis. Particular attention was paid to statistical approaches of handling dropouts. Results A total of 33 articles including 27 trials totaling 6575 patients with active treatment were included in the systematic review. Seven randomized controlled trials were eligible for the meta‐analysis. Over a 24 week treatment period infliximab [risk difference (RD) 78%, 95% confidence interval (CI) 72–83%] and ustekinumab 90 mg every 12 weeks (RD 77%, 95% CI 71–83%) were the most efficacious treatments. Adalimumab (RD: 60%, 95% CI 45–74%) showed results within the range of different etanercept dosages (etanercept 50 mg once weekly: RD 62%, 95% CI, 52–72%), (etanercept 25 mg twice weekly: RD 45%, 95% CI 34–56%), (etanercept 50 mg twice weekly: RD 56%, 95% CI 49–62%) and (etanercept 50 mg twice weekly until week 12, then 25 mg twice weekly: RD 50%, 95% CI 42–57%). After 24 weeks a decrease in efficacy for inflximab, adalimumab and etanercept was observed. Conclusions More sufficient data is required to draw reliable conclusions in extended long‐term treatment and head‐to‐head comparisons are necessary.     

Economic evaluation of systemic therapies for moderate to severe psoriasis

Background New biologics have dramatically changed therapeutic options for psoriasis, albeit at additional cost. Objectives To determine the cost‐effectiveness and optimal treatment sequence for moderate to severe psoriasis. Methods Psoriasis Area and Severity Index (PASI) response rates from 22 randomized controlled trials evaluating biologic (adalimumab, efalizumab, etanercept, infliximab) and nonbiologic systemic (methotrexate, ciclosporin) agents were considered. Short‐term efficacy was based on relative probabilities of achieving PASI response (50/75/90) in a meta‐analysis of trials. Published evidence and assumptions were used to predict long‐term efficacy. Treatment benefits were determined by the relationship between PASI response and the EuroQOL 5D health utility measure. Costs included therapy, administration, monitoring and hospitalization. Incremental cost‐effectiveness ratios (ICERs) were calculated and treatments ranked relative to supportive care. Results Infliximab provided the most incremental quality‐adjusted life‐years (QALYs) vs. supportive care (0·18 QALYs; 95% confidence interval, CI 0·13–0·24), followed by adalimumab (0·16 QALYs; 95% CI 0·11–0·22). Methotrexate and ciclosporin were less beneficial (0·13 and 0·08 QALYs, respectively) but were cost saving and considered the first two treatments in the optimal sequence. Comparing biologics, adalimumab was most cost effective (ICER £30 000 per QALY), followed by etanercept (£37 000 per QALY), efalizumab (£40 000 per QALY) and infliximab (£42 000 per QALY). Conclusions Methotrexate and ciclosporin are cost effective but require monitoring for toxicities. Of the biologics, adalimumab was most cost effective following conventional systemic treatment failure or inadequate response. Payers and policymakers will have to decide how to utilize their budgets effectively for treating patients with moderate to severe psoriasis.     

The interpretation of long‐term trials of biologic treatments for psoriasis: trial designs and the choices of statistical analyses affect ability to compare outcomes across trials

Psoriasis is a chronic disease requiring long‐term therapy, which makes finding treatments with favourable long‐term safety and efficacy profiles crucial. The goal of this review is to provide the background needed to evaluate properly long‐term studies of biologic treatments for psoriasis. Firstly, important elements of design and analysis strategies are described. Secondly, data from published trials of biologic therapies for psoriasis are reviewed in light of the design and analysis choices implemented in the studies. Published reports of clinical trials of biologic treatments (adalimumab, alefacept, etanercept, infliximab or ustekinumab) that lasted 33 weeks or longer and included efficacy results and statistical analysis were reviewed. Study designs and statistical analyses were evaluated and summarized, emphasizing patient follow‐up methods and handling of missing data. Various trial designs and data handling methods are used in long‐term studies of biologic psoriasis treatments. Responder analyses in long‐term trials can be conducted in responder enrichment, re‐treated nonresponder or intent‐to‐treat trials. Missing data can be handled in four ways, including, from most to least conservative, nonresponder imputation, last‐observation‐carried‐forward, as‐observed analysis and anytime analysis. Long‐term clinical trials have shown that adalimumab, alefacept, etanercept, infliximab and ustekinumab are efficacious for psoriasis treatment; however, without common standards for these trials, direct comparisons of these agents are difficult. Understanding differences in trial design and data handling is essential to make informed treatment decisions.     

Obesity and psoriasis: body weight and body mass index influence the response to biological treatment

Patients with psoriasis, in particular those requiring systemic treatment, tend to be above normal weight. Obesity is associated with psoriasis and contributes significantly to the increased cardiovascular risk in these patients. Most biologics used to treat psoriasis in the European Union are fixed dosed treatments: etanercept, adalimumab and ustekinumab. Apart from infliximab, dosing regimens do not account for weight, with the exception of ustekinumab, the dose of which should be doubled in patients weighing more than 100 kg. The aim of this study was to review the available evidence on the association of obesity and psoriasis, and the effect of body weight or obesity on the efficacy of biologics as well as their practical implications in daily practice. A review was performed of the literature relating to obesity and psoriasis and weight effect, including subgroup analyses, on the efficacy of the biologicals available for treatment of psoriasis in the European Union, namely adalimumab, etanercept, infliximab and ustekinumab. Optimal responses with fixed dose biological agents are less frequent in patients with increasing weight, especially above 100 kg, who account for approximately 25% to 30% of patients in clinical trials. Body weight effect on drug clearance might partly account for this fact. The data are limited to subgroup analyses, often with no statistical significance reported. Further studies, including weight‐based subanalysis of clinical trials and pharmacoeconomic evaluations, are required to assess the issue of body weight and response to therapy of the biologics. Infliximab response appears to be independent of body mass index. Possible weight‐based dose adjustments and the impact of treatment on body weight changes also require additional study.     

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.     

Benefit‐risk assessment of tumour necrosis factor antagonists in the treatment of psoriasis

Background Safety of tumour necrosis factor (TNF) antagonists is a primary concern for clinicians prescribing them to patients with psoriasis. Objectives To determine the benefit‐risk balance of TNF antagonists in psoriasis. Methods Through integrated analyses of published literature, we calculated the number needed to treat (NNT) for various efficacy measures and the number needed to harm (NNH) for various adverse events for approved dosing regimens of adalimumab, etanercept and infliximab. Integrated analyses that included open‐label safety data from TNF‐antagonist clinical trials were also conducted. Results PASI 75 treatment effect data from the literature result in NNT values of 1·6 (95% confidence interval, CI 1·5–1·7) for adalimumab 40 mg every other week; 3·2 (95% CI 2·8–3·7) for etanercept 50 mg weekly or 25 mg twice weekly, and 2·3 (95% CI 2·1–2·5) for etanercept 50 mg twice weekly; and 1·4 (95% CI 1·3–1·5) for infliximab 5 mg kg^?1 dosing. For serious noninfectious, serious infectious and malignant adverse events, point estimates of the NNHs are generally at least two orders of magnitude larger than the NNTs, and the 95% CIs for the NNHs for adalimumab, etanercept and infliximab overlap. Analyses that included open‐label data corroborated, with increased exposure to study agents, the low risk of adverse events observed in placebo‐controlled periods. Conclusions These analyses demonstrated that, during the initial year of treatment, the likelihood of success with anti‐TNF therapy for psoriasis was several orders of magnitude greater than the likelihood of serious toxicity.     

Placebo response in relation to clinical trial design: a systematic review and meta-analysis of randomized controlled trials for determining biologic efficacy in psoriasis treatment

There is a need to better define how the efficacy of investigational drugs is affected by study design, implementation, and placebo responses in randomized controlled trials. The improvements observed in placebo groups within trials examining psoriasis treatments may be partially due to study design and implementation. We conducted a systematic review of randomized placebo-controlled trials assessing the efficacy of biologics in the treatment of psoriasis and psoriatic arthritis to evaluate rates of placebo and active drug responders to determine specific factors within study design that may contribute to placebo responses. We included randomized, placebo-controlled trials of etanercept, infliximab, adalimumab, golimumab, ustekinumab, alefacept, and efalizumab that utilized Psoriasis Area Severity Index as an outcomes measure. We compared the rates of the placebo treatment arm versus the active drug arm achieving 75?% improvement of Psoriasis Area Severity Index. 31 trials involving 8285 active treatment and 3999 placebo patients were included. Rates of placebo responders (4.14?%) were significantly lower than active drug responders (48.4?%). The overall odds ratio calculated was 23.94 (p?<?0.0001, 95?% CI 16.02–35.76). Binomial regression models showed that treatment indication, randomization fraction, a PASI inclusion requirement, and the time period of outcomes measure documentation affect placebo responses. Placebo responses seen in randomized controlled trials evaluating biologics in the treatment of psoriasis are not likely due to a physiologic mechanism, but may be secondary to chronic disease course and factors of clinical trial design and implementation.     

Impact of biologic therapies on risk of major adverse cardiovascular events in patients with psoriasis: systematic review and meta‐analysis of randomized controlled trials

Concerns have been raised regarding an increased risk of major adverse cardiovascular events (MACEs) (myocardial infarction, cerebrovascular accident or cardiovascular death) in patients treated with anti‐interleukin (IL)‐12/23 agents for moderate‐to‐severe psoriasis. We aimed to examine the risk of MACEs in adult patients with plaque psoriasis that are exposed to biologic therapies via a meta‐analysis of randomized controlled trials (RCTs). Data were obtained from systematic searches in the Cochrane Library, MEDLINE and Embase, U.S. Food and Drug Administration, European Medicines Agency, individual pharmaceutical companies online search platforms and five trials registers (up to 31 March 2016). We selected RCTs reporting adverse events in adults with plaque psoriasis receiving at least one licensed dose of biologic therapy, conventional systematic therapy or placebo. We calculated Peto odds ratios (ORs) with 95% confidence intervals (CIs) and calculated I² statistics to assess heterogeneity. Overall, 38 RCTs involving 18 024 patients were included. No MACEs were observed in 29 studies, while nine RCTs reported 10 patients experiencing MACEs. There was no statistically significant difference in risk of MACEs associated with the use of biologic therapies overall (OR 1·45, 95% CI 0·34–6·24); tumour necrosis factor‐α inhibitors (adalimumab, etanercept and infliximab) (OR 0·67, 95% CI 0·10–4·63); anti‐IL‐17A agents (secukinumab and ixekizumab) (OR 1·00, 95% CI 0·09–11·09) or ustekinumab (OR 4·48, 95% CI 0·24–84·77). No heterogeneity was observed in these comparisons. In conclusion, the limited existing evidence suggests that licensed biologic therapies are not associated with MACEs during the short randomized controlled periods in clinical trials.     

Safety,efficacy and drug survival of biologics and biosimilars for moderate‐to‐severe plaque psoriasis

Psoriasis, a common disease affecting 2‐3% of the world's population, may in moderate‐to‐severe cases require systemic treatment with biological drugs (biologics). Treatment is usually permanent, but these drugs may loose their effect over time. When the patent for the original (originator) drug expires, other companies can produce a biosimilar, i.e. a drug that is very similar (but not completely identical, since biologics are derived from living human genes) to the originator. This Danish study compared safety, efficacy, and drug survival (i.e. how long patients stay on therapy) for five biologics: adalimumab, etanercept, infliximab, secukinumab, and ustekinumab. The study also compared the originator versions of etanercept and infliximab to their biosimilar versions. Data was examined from 3495 treatment series in 2161 patients. Drug survival was significantly higher for ustekinumab than for the other drugs. Secukinumab had the shortest survival and thereby also the highest risk of discontinuation of therapy. Adverse events also occurred the most frequently with secukinumab. Switching from an originator to a biosimilar version did not significantly affect drug survival. Among patients that obtained complete skin clearance, this occurred more rapidly for those treated with secukinumab as their first‐ever biologic. Over a 10‐year period, discontinuation of therapy occurred in 45·7% (adalimumab), 64·9% (etanercept), and 54·4% (infliximab) of patients. Ustekinumab and secukinumab have only been available for 8 and 2 years, respectively, during which time 30·3% and 28·8% of patients discontinued these therapies, respectively. Over time, response to therapy was generally highest for ustekinumab, followed by adalimumab.     

Relationship between the efficacy of biologics and clinical plaque psoriasis subtypes in Japanese patients: A single‐center pilot study

Although biologics for plaque psoriasis brought epoch‐making efficacy, not all patients achieve treatment success with all reagents. The aim of this study was to clarify the correlation between clinical plaque psoriasis subtypes, age at onset, and the efficacy of biologics. Clinical records for patients with plaque psoriasis at Fukuoka University Hospital were reviewed retrospectively. The efficacy of biologics was compared using the survival of the first biologics administered in treatment‐naïve patients. The survival of infliximab, adalimumab, and ustekinumab were followed until December 2016. The patients were clinically classified into three subtypes: small, large, or gigantic plaques using the size of the plaques on the back; early onset psoriasis (EOP, onset <40 years); or late‐onset psoriasis (LOP, ≥40 years). Eighty‐seven patients were enrolled. The survival of biologics was significantly better in large plaques compared with small or gigantic plaques (P = 0.0007). In patients treated with tumor necrosis factor (TNF) inhibitors, large plaques had significantly better survival than did the other types (P = 0.0122), while ustekinumab showed good survival in all three subtypes. The survival of biologics was numerically better in EOP than in LOP, but this was not significant. The efficacy of TNF inhibitors was different among clinical subtypes. Psoriatic patients with small plaques may be less responsive to TNF inhibitors. Further studies are needed.     

Successful adalimumab treatment of a psoriasis vulgaris patient with hemodialysis for renal failure: A case report and a review of the previous reports on biologic treatments for psoriasis patients with hemodialysis for renal failure

The efficacy and safety of biologic treatments have been established in patients with moderate to severe psoriasis, but there are few reports on biologic therapy for patients with psoriasis complicated by end‐stage renal failure on hemodialysis (HD). In this report, we demonstrated the efficacy and safety of adalimumab for patients with severe psoriasis on HD. A 46‐year‐old Japanese man with a 14‐year history of psoriasis was referred to our clinic in September 2009. He had developed hypertension and renal failure during a 7‐year history of cyclosporin treatment. With the infliximab treatment, he achieved 75% improvement of the Psoriasis Area and Severity Index (PASI) score within 3 months from the PASI of 42.3 before the treatment. However, his renal failure gradually deteriorated, and HD was initiated at 1 year after the introduction of infliximab. Because of hydration during the i.v. injection of infliximab, he developed pulmonary edema with every infliximab treatment after starting HD. We switched to ustekinumab treatment, but his psoriasis was not improved. Then, we switched to adalimumab and achieved a PASI‐100 response within 2 months. The patient received adalimumab treatment for more than a year without any adverse effects. In addition to our case, five articles reported cases of psoriasis patients with renal failure on HD who were treated with biologics. The psoriatic lesions were improved by biologics in these cases, and no severe adverse effects on the renal function were reported. Thus, biologics are a reasonable treatment option for patients with severe psoriasis with renal failure on HD.     

Systematic review on the maintenance of response during systemic antipsoriatic therapy

As a chronic disease psoriasis often requires long‐term treatment. Successful continuation of therapy during a maintenance phase is therefore important. A systematic review was performed on the efficacy of psoriasis drugs during maintenance treatment in patients who had achieved sufficient treatment success during the induction period. Maintenance therapy is defined as treatment during the period after successful induction therapy. Inclusion criteria were prospective studies with systemic therapies recommended by the 2009 European psoriasis guidelines (plus ustekinumab), and a study population that had achieved a defined treatment response criterion after induction therapy within a period of ≥ 6 months. Maintenance studies on conventional treatments were identified for ciclosporin (CSA) only (no studies investigating acitretin, methotrexate or ustekinumab were found). Compared with placebo, CSA was shown to be effective in maintenance therapy, yet CSA 1·5 mg kg^?1 seems to be insufficient to maintain disease control. Based on the evidence, it is uncertain whether there is any difference between daily or intermittent treatment. For biologics, maintenance data were available for adalimumab, etanercept and infliximab. No differences in 75% improvement in Psoriasis Area and Severity Index (PASI 75) response were identified between adalimumab 40 mg once and twice a month. Continuous infliximab treatment was shown to be superior to as‐needed treatment. For etanercept, only observational postrandomized controlled trial data were available, indicating a maintained PASI 75 response in approximately three‐quarters of patients during long‐term treatment. Only limited evidence is available for a conclusion on how patients with an adequate response should be optimally treated during the maintenance period. A clear ranking of the available treatments is not yet possible.     

Efficacy and safety of tofacitinib for moderate‐to‐severe plaque psoriasis: a systematic review and meta‐analysis of randomized controlled trials

The effects of tofacitinib in treating moderate‐to‐severe plaque psoriasis were unclear. We aimed to assess the effects of tofacitinib in treating moderate‐to‐severe plaque psoriasis. We searched PubMed, Cochrane Central Register of Controlled Trials and EMBASE for relevant randomized controlled trials (RCTs) and conducted a systematic review and meta‐analysis. Four RCTs with 2724 participants were included. Compared to placebo, tofacitinib significantly improved psoriasis {≥75% reduction in the Psoriasis Area and Severity Index score: 5 mg BID: risk difference (RD) 0.32 [95% confidence interval (CI) 0.28–0.35], 10 mg BID: RD 0.51 (95% CI 0.43–0.58); ≥90% reduction in the Psoriasis Area and Severity Index score: 5 mg BID: RD 0.19 (95% CI 0.17–0.22), 10 mg BID: RD 0.36 (95% CI 0.31–0.42); Physician's Global Assessment 0/1: 5 mg BID: RD 0.31 (95% CI 0.27–0.35), 10 mg BID: RD 0.48 (95% CI 0.44–0.53)} and participants’ life quality [Dermatology Life Quality Index 0/1: 5 mg BID: RD 0.24 (95% CI 0.20–0.2), 10 mg BID: RD 0.36 (95% CI 0.33–0.40)]. Tofacitinib was associated with an increase in minor adverse events [upper respiratory tract infection: 5 mg BID: RD 0.02 (95% CI 0.00–0.03), 10 mg BID: RD 0.02 (95% CI 0.00–0.04); hypercholesterolaemia: 5 mg BID: RD 0.02 (95% CI 0.01–0.04), 10 mg BID: RD 0.02 (95% CI 0.01–0.04)]. In conclusion, tofacitinib may be a treatment option for moderate‐to‐severe plaque psoriasis that is unresponsive to other therapies and patients who are intolerable to other therapies or prefer oral medications.     

Antidrug antibodies in psoriasis: a systematic review

Antidrug antibodies (ADAs) against biological agents may be clinically significant and potentially alter a biological drug's treatment efficacy. This systematic review aims to (i) determine the prevalence of ADAs against infliximab, etanercept, adalimumab and ustekinumab in patients with psoriasis; (ii) ascertain whether ADAs are associated with changes in drug efficacy; and (iii) explore the use of concomitant methotrexate to prevent ADA formation. Through a systematic search using Medline and Embase from 29 January 1950 to 29 March 2013, we identified 25 studies that met the inclusion criteria. Of 7969 patients with psoriasis, 950 tested positive for ADAs. Antibodies against infliximab, etanercept, adalimumab and ustekinumab were reported in 5·4–43·6%, 0–18·3%, 6–45% and 3·8–6% of patients, respectively. Anti‐infliximab antibodies were associated with lower serum infliximab concentrations in three studies, and decreased treatment response in five studies. ADAs against etanercept were non‐neutralizing and not associated with any apparent effects on clinical response. Antiadalimumab antibodies were associated with lower serum adalimumab concentrations in three of five studies, and reduced clinical efficacy in four studies. Two of six studies reported that antiustekinumab antibodies were associated with lower Psoriasis Area and Severity Index responses, and three ustekinumab studies noted that most of these antibodies were neutralizing. Although the use of concomitant methotrexate with biological agents to prevent ADA formation in other immune‐mediated diseases is promising, their use in psoriasis is sparse. ADA development remains a challenge with biological therapies and therefore should be considered in patients with psoriasis who experience diminished treatment response.     

Comparative Efficacy of Biologics in Psoriasis

Background: Psoriasis is a chronic, immune-mediated skin disease that also has systemic manifestations. Safe and effective long-term treatments are needed. Biologic treatments that inhibit the immunopatho-genesis of psoriasis have helped meet this need. Purpose: The purpose of this study was to compare the efficacy of biologic therapies used for psoriasis. Methods: A literature search was performed using PubMed and the keywords ‘(PASI-75 OR efficacy) AND psoriasis AND (adalimumab OR alefacept OR etanercept OR infliximab OR ustekinumab).’ Randomized, double-blind, and placebo-controlled studies on US FDA-approved biologics were selected. Studies assessing the proportion of subjects achieving 75% improvement in Psoriasis Area and Severity Index (PASI-75) within a 12-week period were included. Studies on pediatric populations and psoriatic arthritis were excluded. The weighted average of PASI-75 for each reported regimen was calculated to determine the efficacy of biologic agents used for moderate-to-severe psoriasis. Tolerance and secondary efficacy measures were also examined for the selected studies. Results: FDA-approved regimens of adalimumab, infliximab, ustekinumab, and alefacept were effective in treating moderate-to-severe psoriasis. Weighted average PASI-75 scores for infliximab, ustekinumab, adalimumab, etanercept, and alefacept were 78.6%, 72.1%, 70.5%, 48.1%, and 21%, respectively. Limitations: The comparative efficacy of biologic agents data was limited to 12 weeks, thus generalizing the results to longer treatment periods may not be accurate. Conclusions: Various biologic agents for psoriasis were effective at 12 weeks in placebo-controlled trials. Available data cannot fully account for situations in clinical practice, in which combination and longer duration of therapy may be required. When choosing the most effective or best agent, multiple factors should be considered including patient preference, cost, tolerance, adverse effects, dosing schedule, and mode of administration.     

Efficacy and safety of systemic treatments in psoriatic arthritis: a systematic review,meta‐analysis and GRADE evaluation

Twenty per cent of patients with plaque psoriasis also have psoriatic arthritis – a disease affecting joints and entheses. Different treatment options exist but currently no succinct systematic overview exists. A systematic review of approved systemic treatments for psoriatic arthritis was conducted. We systematically searched in three databases (last update September 2017). Data were extracted for ACR20/50, HAQ‐DI, SF‐36 and adverse/serious adverse events after 16–24 weeks. We assessed the quality of evidence using GRADE. Twenty trials were included. Three trials compared two active substances. Results for ACR20 were infliximab + methotrexate vs. methotrexate: RR 1.40 (95% CI 1.07–1.84) very low quality evidence; ixekizumab Q2W vs. adalimumab Q2W: RR 1.08 (95% CI 0.86–1.36) very low quality, leflunomide vs. methotrexate: RR 1.01, (95% CI 0.84–1.21) low quality. Eighteen drug vs. placebo comparisons were included. For ACR20/50, HAQ‐DI and SF‐36, the active treatment was efficacious and the quality of the evidence was mostly moderate to low (15 of 18 comparisons). The quality of evidence for (serious) adverse events was mostly low; differences were rare. In three placebo‐controlled comparisons, leflunomide, MTX and sulfasalazine failed to show statistical superiority for ACR. Besides the established treatment of anti‐TNF antibodies and ustekinumab for psoriatic arthritis, the newer treatment options of IL17 antibodies and apremilast are also effective for the treatment of psoriatic arthritis. Based on just one comparative trial and one drug each, the new class of anti‐IL 17 antibodies appears to be equally effective as the group of anti‐TNF antibodies; for apremilast, this is yet unclear.     

Efficacy of biologics in the treatment of moderate to severe psoriasis: a network meta-analysis of randomized controlled trials

Background Ustekinumab, a novel monoclonal antibody for the treatment of moderate to severe plaque‐type psoriasis, has recently received regulatory approval in Europe, bringing the total number of biologic agents licensed in this indication to five. To assist treatment selection in daily practice it is essential to understand the benefit/risk profile of these agents and in the absence of a clinical trial comparing all available biologics a number of reviews have used statistical techniques to generate estimates of the comparative effectiveness of these therapies through the available network of randomized clinical trials. These estimates have previously been published for a limited range of psoriasis biologic treatments, although, to date no review has compared all the currently available agents in Europe. Objectives To estimate the comparative effectiveness of all biologic agents indicated in the treatment of moderate to severe psoriasis currently available in Europe based on the primary trial endpoints. Methods A number of databases were searched for details of randomized controlled trials of available biologics in the treatment of plaque‐type psoriasis in adults. Comparative effectiveness was estimated based on the reported Psoriasis Area and Severity Index (PASI) 50, 75 and 90 response rates. A network meta‐analysis conducted on the ordered probit scale and implemented as a Bayesian hierarchical model provided estimates for the probability of response and relative risk vs. placebo, based on all observed comparisons. Results Twenty trials were included in the meta‐analysis including patients with a mean disease duration of 18–22 years. Based on the indirect comparison and given a placebo PASI 50 response of 13%, infliximab had the highest predicted mean probability of response at PASI levels 50 (93%), 75 (80%) and 90 (54%), followed by ustekinumab 90 mg at 90%, 74% and 46%, respectively, and then ustekinumab 45 mg, adalimumab, etanercept and efalizumab. Conclusions The ordered probit model allowed a quantitative comparison of all currently licensed biologics, providing estimates on comparative effectiveness and a suggested ranking of treatments that is of potential use to decision‐makers. However, the analysis is based on indirect comparisons of the primary endpoint reported from short‐term randomized trials.     

Safety and effectiveness of ustekinumab and antitumour necrosis factor therapy in patients with psoriasis and chronic viral hepatitis B or C: a retrospective,multicentre study in a clinical setting

Background Both the safety and efficacy of biologic therapy may be affected in the presence of highly prevalent chronic viral hepatitis. Objectives To evaluate the safety and effectiveness of ustekinumab and antitumour necrosis factor therapy in patients with psoriasis and concomitant chronic viral hepatitis. Methods This was a retrospective, multicentre study. Twenty‐five patients with psoriasis and concurrent hepatitis C virus (HCV) (20 patients) or hepatitis B virus (HBV) (five patients) infection who had received at least one biologic agent (etanercept, 21 treatments; adalimumab, four; ustekinumab, four; infliximab, two) were included. Clinical, imaging and laboratory data were recorded. Results In the case of HCV infection, the majority of the patients did not exhibit increases in their viral load or serum liver tests. Aspartate aminotransferase, alanine aminotransferase and gamma glutamyl transpeptidase were doubled from the baseline measurement in only one patient treated with etanercept. Two other cases exhibited viral load increases during the follow‐up period. In total, 18 of the 26 treatments achieved a 75% improvement in their Psoriasis Area and Severity Index (PASI 75) score during the follow‐up period. Two patients treated with etanercept were diagnosed with hepatocellular carcinoma. In the case of HBV infection, all of the patients were being treated with antiviral therapy, and none presented significant variations in viral load or serum liver enzymes. All patients achieved a PASI 75 during follow‐up. Conclusions Biologic therapy was effective and safe for the majority of our patients with HCV and HBV infection, although there may be a risk of reactivation or aggravation. We describe the first cases to receive ustekinumab. The use of biologics should be limited to those cases in which the risk–benefit ratio is justified.     

Efficacy and safety of biologics in erythrodermic psoriasis: a multicentre, retrospective study

Background Even though efficacy of biologics has been extensively studied in psoriasis vulgaris, studies in erythrodermic psoriasis, the most severe form of the disease, have been scarcely reported. Objectives To address the efficacy and safety of biologics in patients with erythrodermic psoriasis. Methods A multicentre national retrospective study was performed using the French Psoriasis Group network. Patients showing psoriasis involving at least 90% of body surface area (BSA), and in whom severity of the disease had been evaluated before and after 3 and/or 6 months of treatment with biologics, were enrolled in the study. Results were expressed using intention‐to‐treat analysis. Results We included 28 patients, representing 42 flares of erythrodermic psoriasis treated with infliximab (n = 24), adalimumab (n = 7), etanercept (n = 6), ustekinumab (n = 3) or efalizumab (n = 2). A 75% improvement of BSA or Psoriais Area and Severity Index 12–14 weeks after treatment onset was reached in 48% of flares treated with infliximab, in 50% of those treated with adalimumab and in 40% of those treated with etanercept. Twelve serious adverse events, consisting of bacterial infection in seven of them, were observed. Biological treatment was discontinued for safety concern in 19% of cases. A given biologic was administered for up to 48 weeks in 34% of flares. Conclusions Biologics show overall good short‐term efficacy, but treatment switch due to lack of efficacy or side‐effects is frequently observed on a longer term, with only one‐third of patients still receiving the same drug after 1 year. The most significant safety concern consists of severe infections.