Combining biologics with methotrexate in psoriasis: a systematic review

Bezooijen, Ji S. van; Prens, Errol P.; Pradeepti, M.S.; Atiqi, Roya; Schreurs, Marco W. J.; Koch, Birgit C. P.; Gelder, Teun van; Doorn, Martijn van

doi:10.1111/bjd.13573

Cited by 10 publications

(10 citation statements)

References 18 publications

(8 reference statements)

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“…The efficacy rates observed in our study [23] are comparable with those of Gottlieb and his group [9,12] whereby 239 patients were randomized to etanercept monotherapy or etanercept with methotrexate (MTX). After 24 weeks, the PASI-75 was significantly higher in the etanercept with MTX group than in the etanercept monotherapy group (77.3 vs. 60.3%; p < 0.0001).…”

Section: Discussionsupporting

confidence: 83%

“…In daily practice MTX is more frequently combined with biologics than fumarates, because it is assumed that (low-dose) MTX increases the clinical efficacy of biologics by reducing the development of antidrug antibodies [23,24]. Anti-etanercept antibodies have only sporadically been observed in clinical studies, indicating that loss of clinical efficacy for etanercept is probably caused by other, yet unidentified factors [25].…”

Section: Discussionmentioning

confidence: 99%

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Combination Therapy of Etanercept and Fumarates versus Etanercept Monotherapy in Psoriasis: A Randomized Exploratory Study

Bezooijen¹,

Balak²,

Doorn³

et al. 2016

Dermatology

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Background: Biologics are a safe and efficacious therapy for psoriasis. The drug survival of biologics may be disappointing, primarily due to loss of efficacy. Therefore, safe combination treatments are sought to improve their clinical response. Objective: To assess the efficacy, safety and tolerability of the combination therapy of etanercept with fumarates versus etanercept monotherapy. Methods: Thirty-three patients with psoriasis were randomized 1:1 to receive etanercept combined with fumarates or etanercept monotherapy. The primary outcome measure was the difference in PASI-75 response after 24 weeks; additionally, a longitudinal analysis was performed. An important secondary outcome measure was the proportion of patients with a Physician Global Assessment (PGA) of clear or almost clear. Adverse events were collected throughout the study. Results: In the combination therapy group, 78% (14 out of 18 patients) reached PASI-75 at week 24 versus 57% (8 out of 14 patients) in the monotherapy group (p = 0.27). The longitudinal analysis showed a PASI reduction of 5.97% per week for the combination therapy group and of 4.76% for the monotherapy group (p = 0.11). In the combination therapy group, 94% (17 out of 18 patients) of patients had a PGA of clear/almost clear versus 64% (9 out of 14 patients) in the monotherapy group (p = 0.064). The incidence of mild gastrointestinal complaints was higher in the combination group than in the monotherapy group. Conclusion: Using the PGA, combination therapy showed a trend towards faster improvement in the first 24 weeks. The difference in the PASI score between the two groups was not statistically significant. Addition of fumarates to etanercept for 48 weeks appeared safe with an acceptable tolerability.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Combination Therapy of Etanercept and Fumarates versus Etanercept Monotherapy in Psoriasis: A Randomized Exploratory Study

Bezooijen¹,

Balak²,

Doorn³

et al. 2016

Dermatology

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“…Although concomitant MTX usage has been shown to be associated with a better persistence of biologicals in rheumatological settings, there is no conclusive evidence in psoriasis about additional MTX as a positive predictor (24,25). In a systematic review, Bezooijen et al selected eight studies, which generally showed that combination therapy of biologicals and MTX had higher efficacy than biological monotherapy, which could also indicate a positive effect of MTX on the drug survival; however, persistence was not investigated in this study (26). On the other hand, Menter and colleagues unexpectedly reported that patients receiving MTX were significantly more likely to discontinue biological treatment compared with those without concomitant MTX in bionaïve group, but not in biologic experienced patients (20).…”

Section: Discussionmentioning

confidence: 91%

Long-term drug survival and predictor analysis of the whole psoriatic patient population on biological therapy in Hungary

Pogácsás

Borsi

Takács

et al. 2017

Journal of Dermatological Treatment

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Persistence is an important component of therapeutic success, which depends on a variety of factors. Persistence measured under optimal conditions during clinical trials does not necessarily coincide with persistence observed in the real-world settings. The aim of the present study was to compare persistence rate of TNF-alpha inhibitors and interleukin 12/23 inhibitor in all psoriasis patients in Hungary, as well as to analyze the predictors of persistence. Data collected from 1263 patients over a period of 46 months were subjected to a retrospective analysis. Drug survival rate has been calculated according to Kaplan-Meier analysis and Cox regression was used to study the predictors. The overall persistence rate for the four biologicals exceeded 60% after 3 years. The persistence rate of ustekinumab at 3 years was 67.83%, which was superior compared to that of the TNF-alpha inhibitors, where the mean persistence rate was shown to be 50.76% (p < .05). Male patients showed significantly higher persistence than females (HR ¼ .76, p < .05 CI: 0.63, 0.92). Age, therapy-naïve status and use of concomitant MTX did not have significant effect on drug survival. Persistence rate of ustekinumab was significantly higher than that of TNF-alpha inhibitors, and among predictors, only male gender influenced persistence significantly. ARTICLE HISTORY

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“…The two RCTs on etanercept and MTX provided promising results with superior efficacy of etanercept with MTX compared to etanercept monotherapy. RCTs investigating combined treatment with adalimumab and MTX are lacking [ 19 , 26 ].…”

Section: Introductionmentioning

confidence: 99%

Optimizing adalimumab treatment in psoriasis with concomitant methotrexate (OPTIMAP): study protocol for a pragmatic, single-blinded, investigator-initiated randomized controlled trial

Busard

Menting

Bezooijen

et al. 2017

Trials

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BackgroundThe introduction of anti-tumor necrosis factor medications has revolutionized the treatment of psoriasis with achievement of treatment goals (Psoriasis Area and Severity Index score 75, remission) that are not usually met with conventional systemics. Nevertheless, some patients continue to experience persistent disease activity or treatment failure over time. Strategies to optimize treatment outcomes include the use of concomitant methotrexate, which has demonstrated beneficial effects on pharmacokinetics and treatment efficacy in psoriasis and other inflammatory diseases.MethodsThis is an investigator-initiated, multicenter randomized controlled trial (RCT) designed to compare the combination treatment of adalimumab and methotrexate with adalimumab monotherapy in patients with psoriasis. The primary outcome is adalimumab drug survival at week 49. Other outcomes include improvement in disease severity and quality of life, tolerability, and safety. Moreover, anti-adalimumab antibodies and adalimumab serum concentrations will be measured and correlations between genotypes and clinical outcomes will be assessed. Patient recruitment started in March 2014. Up to now, 36 patients have been randomized. Many more patients have been (pre)screened. A total of 93 patients is desired to meet an adequate sample size. In our experience, the main limitation for recruitment is prior adalimumab therapy and intolerability or toxicity for methotrexate in the past.DiscussionOPTIMAP is the first RCT to examine combination therapy with adalimumab and methotrexate in a psoriasis population. With data derived from this study we expect to provide valuable clinical data on long-term treatment outcomes. These data will be supported by assessment of the impact of concomitant methotrexate on adalimumab pharmacokinetics. Furthermore, the influence of several single nucleotide polymorphisms on adalimumab response will be analyzed in order to support the development of a more personalized approach for this targeted therapy.Trial registration NTR4499. Registered on 7 April 2014.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-017-1777-y) contains supplementary material, which is available to authorized users.

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Combining biologics with methotrexate in psoriasis: a systematic review

Cited by 10 publications

References 18 publications

Combination Therapy of Etanercept and Fumarates versus Etanercept Monotherapy in Psoriasis: A Randomized Exploratory Study

Combination Therapy of Etanercept and Fumarates versus Etanercept Monotherapy in Psoriasis: A Randomized Exploratory Study

Long-term drug survival and predictor analysis of the whole psoriatic patient population on biological therapy in Hungary

Optimizing adalimumab treatment in psoriasis with concomitant methotrexate (OPTIMAP): study protocol for a pragmatic, single-blinded, investigator-initiated randomized controlled trial

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