Efficacy and safety of infliximab vs. methotrexate in patients with moderate-to-severe plaque psoriasis: results of an open-label, active-controlled, randomized trial (RESTORE1)

Barker, Jonathan; Hoffmann, Matthias; Wozel, Gottfried; Ortonne, Jean Paul; Zheng, Hong; Hoogstraten, Hubert van; Reich, Kristian

doi:10.1111/j.1365-2133.2011.10615.x

Cited by 178 publications

(135 citation statements)

References 14 publications

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“…In all, 38 RCTs (identified in 38 reports)20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57 met the eligibility criteria and were included, as shown in Figure 1. These trials involved a total of 18 024 patients with plaque psoriasis.…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2017

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SummaryConcerns 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 I 2 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.

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Section: Resultsmentioning

confidence: 99%

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

et al. 2017

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“…The starting dosing was based on the results of three previous trials in which starting doses between 5 to 15 mg with different subsequent up-titration schemes were not associated with differences in the safety profile. [8][9][10] Subcutaneous administration was chosen because of improved adherence, lower risk of accidental overdosing and higher concentration of MTX-polyglutamates (MTX-PG), the active MTX metabolite. 15,16 The dose escalation scheme followed pharmacokinetic considerations to establish a stable pool of MTX-PG as well as a result of previous clinical observations in psoriasis.…”

Section: Discussionmentioning

confidence: 99%

“…[8][9][10] Different study populations and study designs, however, limit the value of this indirect comparison. In particular two of the previous trials with oral MTX were not placebo-, but active comparator-controlled, 9,10 and one of them was an open-label study. 10 Efficacy tended to increase up to week 24 in this study [PASI75/90=50.5% (46/91)/24.2% (22/91) among patients started on MTX], but this delayed response is difficult to distinguish from effects related to the termination of the blinding and open-label treatment with active drug from week 16 on.…”

Section: Discussionmentioning

confidence: 99%

“…In particular two of the previous trials with oral MTX were not placebo-, but active comparator-controlled, 9,10 and one of them was an open-label study. 10 Efficacy tended to increase up to week 24 in this study [PASI75/90=50.5% (46/91)/24.2% (22/91) among patients started on MTX], but this delayed response is difficult to distinguish from effects related to the termination of the blinding and open-label treatment with active drug from week 16 on. The main difference to oral dosing, in addition to a more rapid onset of efficacy [PASI75 response at week 8 approximately 30% (25/91) in this placebo-controlled study compared to approximately 20% in the previous active comparator-controlled study 8 ], appeared to be a superior and more stable long-term response beyond week 16 and up to 52 weeks of therapy.…”

Section: Discussionmentioning

confidence: 99%

“…Only recently has high-quality data on MTX in psoriasis become available from three studies that tested MTX in comparison to the biologics adalimumab, 8 briakinumab, 9 and infliximab. 10 While these studies differed in their dosing schemes, using MTX starting doses of 5 mg/week in conjunction with either a slower 8 or more rapid uptitration scheme 9 as well as a starting dose of 15 mg/week in one study, 10 they all showed similar induction therapy PASI75 response rates of 36% to 42% after 16 to 24 weeks of treatment. Longer term data showed a low stability of MTX response with high drop-out rates due to loss of efficacy in up to 70% of patients over a one-year period.…”

Section: Introductionmentioning

confidence: 99%

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An intensified dosing schedule of subcutaneous methotrexate in patients with moderate to severe plaque-type psoriasis (METOP): a 52 week, multicentre, randomised, double-blind, placebo-controlled, phase 3 trial

Warren

Mrowietz

Kiedrowski³

et al. 2017

The Lancet

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Background: We report the study of an intensified dosing schedule of subcutaneous methotrexate (MTX) in patients with moderate-tosevere psoriasis. Methods: In this prospective, double-blind, multicentre phase 3 study (METOP) eligible patients were 18 years or older with a diagnosis of chronic plaque psoriasis at least 6 months before baseline, had a psoriasis area and severity index (PASI) of 10 or more or 10% or greater body-surface area involvement or a dermatology life quality index (DLQI) of 10 or more and were naïve to treatment with MTX. Participants were randomly assigned 3:1 by computer-generated random sequence integrated in the electronic data capture system to receive either MTX at a starting dose of 17.5 mg/week or placebo for the first 16 weeks, followed by openlabel MTX treatment of all patients up to 52 weeks (MTX/MTX and PLC/MTX groups, respectively). Dose escalation to 22.5 mg/week was allowed after 8 weeks of MTX therapy if patients failed to achieve an at least 50% improvement of their baseline PASI (PASI50); blinding was maintained by a corresponding volume increase of placebo injections. Treatment was combined with folic acid 5 mg/week. The primary efficacy endpoint was the proportion of patients achieving a PASI75 response at week 16 analysed by intention to treat with non-responder imputation. This study is registered with the European Medicines Agency, EudraCT number 2012-002716-10. Findings: Between February 2013 and May 2015 120 patients were randomly assigned to receive subcutaneous MTX (n=91) or placebo (n=29). The primary endpoint was met; the PASI75 response rate at week 16 was 41% (n=37) in the MTX group compared to 10% (n=3) in the placebo group [p=0.0026; effect size 30.3% (95% CI 15.3-45.3) MTX vs placebo]. Subcutaneous MTX was generally well tolerated; no cases of serious infections, malignancies, major adverse cardiovascular events or deaths were noted. Serious adverse events were observed in 3 patients started on MTX during the 52-week study period. Interpretation: The study documents a favourable 52-week benefit-risk profile of subcutaneous MTX in psoriasis. The route of administration and the intensified dosing schedule should be considered when using MTX in patients with psoriasis. Role of the funding source (see also below)The study was an investigator-initiated trial supported by a grant from Medac to K.R. Manuscript 2 SummaryBackground: We report the study of an intensified dosing schedule of subcutaneous methotrexate (MTX) in patients with moderate-to-severe psoriasis.

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Pathophysiology, Clinical Presentation, and Treatment of Psoriasis

Armstrong

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2020

JAMA

1,258

1,105

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ImportanceApproximately 125 million people worldwide have psoriasis. Patients with psoriasis experience substantial morbidity and increased rates of inflammatory arthritis, cardiometabolic diseases, and mental health disorders.ObservationsPlaque psoriasis is the most common variant of psoriasis. The most rapid advancements addressing plaque psoriasis have been in its pathogenesis, genetics, comorbidities, and biologic treatments. Plaque psoriasis is associated with a number of comorbidities including psoriatic arthritis, cardiometabolic diseases, and depression. For patients with mild psoriasis, topical agents remain the mainstay of treatment, and they include topical corticosteroids, vitamin D analogues, calcineurin inhibitors, and keratolytics. The American Academy of Dermatology-National Psoriasis Foundation guidelines recommend biologics as an option for first-line treatment of moderate to severe plaque psoriasis because of their efficacy in treating it and acceptable safety profiles. Specifically, inhibitors to tumor necrosis factor α (TNF-α) include etanercept, adalimumab, certolizumab, and infliximab. Other biologics inhibit cytokines such as the p40 subunit of the cytokines IL-12 and IL-13 (ustekinumab), IL-17 (secukinumab, ixekizumab, bimekizumab, and brodalumab), and the p19 subunit of IL-23 (guselkumab, tildrakizumab, risankizumab, and mirikizumab). Biologics that inhibit TNF-α, p40IL-12/23, and IL-17 are also approved for the treatment of psoriatic arthritis. Oral treatments include traditional agents such as methotrexate, acitretin, cyclosporine, and the advanced small molecule apremilast, which is a phosphodiesterase 4 inhibitor. The most commonly prescribed light therapy used to treat plaque psoriasis is narrowband UV-B phototherapy.Conclusions and RelevancePsoriasis is an inflammatory skin disease that is associated with multiple comorbidities and substantially diminishes patients’ quality of life. Topical therapies remain the cornerstone for treating mild psoriasis. Therapeutic advancements for moderate to severe plaque psoriasis include biologics that inhibit TNF-α, p40IL-12/23, IL-17, and p19IL-23, as well as an oral phosphodiesterase 4 inhibitor.

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Efficacy and safety of infliximab vs. methotrexate in patients with moderate-to-severe plaque psoriasis: results of an open-label, active-controlled, randomized trial (RESTORE1)

Cited by 178 publications

References 14 publications

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

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

An intensified dosing schedule of subcutaneous methotrexate in patients with moderate to severe plaque-type psoriasis (METOP): a 52 week, multicentre, randomised, double-blind, placebo-controlled, phase 3 trial

Pathophysiology, Clinical Presentation, and Treatment of Psoriasis

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