Abstract
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 registrationNTR4499. Registered on 7 April 2014.
Highlights
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 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
As several polymorphisms have been identified as potential predictors for anti-Tumor necrosis factor (TNF) therapy in psoriasis (e.g., TNFR1B, TNFAIP3, IL12B/IL23R) [6, 27] and other chronic inflammatory diseases (e.g., FcGR and ATG16L1) [28, 29], it will be valuable to detect genetic factors associated with response to adalimumab in order to support personalized care
Summary
This is a multicenter RCT reported according to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines (see Table 1 (SPIRIT table) and Additional file 1 (SPIRIT checklist)). Due to the lack of data in a psoriasis population, the expected clinically relevant difference in drug survival between both treatment groups was hypothesized based on studies performed in patients with RA. The prevalence of (clinically relevant) anti-drug antibody formation is estimated to be 45% in patients on adalimumab monotherapy (a similar percentage is found in patients with psoriasis [31] and around 17% in patients on adalimumab with low-dose (5–10 mg) MTX after 49 weeks [32]. A clear correlation between antibody formation and treatment failure (with subsequent treatment discontinuation) in patients on adalimumab has been demonstrated [31] Based on these data, drug survival is estimated to be 83% (100 minus 17) for the experimental group and 55% (100 minus 45) for the control group after 49 weeks of follow-up. To enlarge the geographical area in which patients can participate in the study and to enhance patient recruitment, three additional hospitals have been activated for patient recruitment: Amphia Hospital (Breda) and Bravis Hospital (Bergen op Zoom) in The Netherlands and Ghent University Hospital in Belgium
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