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



This 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.



OPTIMAP 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.



NTR4499 . Registered on 7 April 2014.
Department of Dermatology, Academic Medical Center, Amsterdam, The Netherlands. c.i.busard@amc.uva.nl.
C I
CI
Busard
Department of Dermatology, Academic Medical Center, Amsterdam, The Netherlands.
S P
SP
Menting
Department of Dermatology, Erasmus University Medical Center, Rotterdam, The Netherlands.
J S
JS
van Bezooijen
Department of Dermatology, Radboud University Medical Center, Nijmegen, The Netherlands.
J M
JM
van den Reek
Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, Amsterdam, The Netherlands.
B A
BA
Hutten
Department of Dermatology, Erasmus University Medical Center, Rotterdam, The Netherlands.
E P
EP
Prens
Department of Dermatology, Radboud University Medical Center, Nijmegen, The Netherlands.
E M
EM
de Jong
Department of Dermatology, Erasmus University Medical Center, Rotterdam, The Netherlands.
M B
MB
van Doorn
Department of Dermatology, Academic Medical Center, Amsterdam, The Netherlands.
P I
PI
Spuls
D000068879:Adalimumab / Q000008:administration & dosage* / Q000009:adverse effects; D001688:Biological Products / Q000008:administration & dosage* / Q000009:adverse effects; D002985:Clinical Protocols; D004359:Drug Therapy, Combination; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects; D009426:Netherlands; D011565:Psoriasis / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D011788:Quality of Life; D012074:Remission Induction; D012107:Research Design; D012720:Severity of Illness Index; D016037:Single-Blind Method; D012867:Skin / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology
D001688:Biological Products; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; D000068879:Adalimumab; D008727:Methotrexate
Combination therapy; Multicenter; Pragmatic; Psoriasis; Randomized controlled trial