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

markdownabstract__Background:__ 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. __Methods:__ 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. __Discussion:__ 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. Trial registration:NTR4499. Registered on 7 April 2014

Reporting of outcomes in randomised controlled trials on nail psoriasis; a Systematic Review

Harmonization of outcome measures is needed to increase the value of clinical trials on nail psoriasis. To provide the first step in core outcome set (COS) development, a systematic review was conducted to identify outcome domains and instruments reported in (ongoing) randomised controlled trials (RCTs) on nail psoriasis. Identified outcome domains included clinical signs, quality of life, symptoms and delivery of care. A NAPSI was most commonly used to assess clinical signs (73.8% of studies). Other outcome instruments used included the NAS, composite fingernail score, a physician global assessment, individual nail features or a combination of these. Heterogeneity in type and reporting (e.g. NAPSI 50, NAPSI 75) of outcome instruments was high and characteristics were often insufficient reported. 43.1% of studies assessed quality of life, with 3.1% of studies using a nail psoriasis specific tool. Assessment of symptoms and delivery of care was limited. In conclusion, heterogeneity in type and reporting of nail psoriasis outcome instruments needs to be addressed in the process towards COS development. Sufficient reporting of instrument characteristics should be encouraged. As nail psoriasis is generally assessed secondary to psoriasis of the skin or joints, collaboration between different research groups in COS development is needed. This article is protected by copyright. All rights reserve

Biologics combined with conventional systemic agents or phototherapy for the treatment of psoriasis: real-life data from PSONET registries.

BACKGROUND Biologics have greatly improved psoriasis management. However, primary and secondary non-response to treatment requires innovative strategies to optimize outcomes. OBJECTIVE To describe the use of combined treatment of biologics with conventional systemic agents or phototherapy in daily clinical practice. METHODS We collected data on frequency of use, demographics, treatment characteristics and drug survival of biologics combined with conventional systemic agents or phototherapy in five PSONET registries. RESULTS Of 9922 biologic treatment cycles, 982 (9.9%) were identified as combination treatment. 72.9% of treatment cycles concerned concomitant use of methotrexate, 25.3% concerned concomitant UVB therapy, acitretin or cyclosporin and 1.8% concerned combined treatment with PUVA, fumaric acids or a second biologic. Substantial variation was detected in type and frequency of combination treatments prescribed across registries. Patients initiated on combined treatment had generally severe disease and were affected with psoriasis for many years. The extent to which patients had been priory treated with biologic monotherapy and the proportion of patients affected with psoriatic arthritis differed between registries. Survival rates for etanercept, adalimumab, infliximab and ustekinumab with methotrexate ranged between 43 and 92%, 28 and 83%, 65 and 87% and 53 and 77%, respectively, across registries after one year with no consistent superior survival for a particular biologic. Longest survival on a biologic combined with methotrexate, acitretin or cyclosporin was 103, 78 and 34 months, respectively. CONCLUSION Methotrexate was the most commonly used concomitant treatment for patients on a biologic. Wide geographical variations in treatment selection and persistence of combination treatment exist. Data derived from ongoing studies may help to determine whether combined treatment is superior to biologic monotherapy

Update richtlijn psoriasis 2017

The update of the NVDV guideline psoriasis 2017 is summarized. In the update the chapters methotrexate, fumaric acid esters, biologics, children, serum concentrations and antibody formation and quality of life are renewed. In addition chapters on secukinumab, apremilast, choice of treatment, combination treatment, psoriatic arthritis and pregnancy and breastfeeding during biologic treatment have been added. The update is based on the NVDV guideline psoriasis 20111, European Dermatology Forum (EDF) guideline Psoriasis 20152 and new search and analyses by the workgroup. The most important differences in the update 2017 compared to the NVDV guideline psoriasis 2011 are discussed