Adalimumab Response Is Improved by Coadministration of Methotrexate in Psoriasis

September 19, 2018

By Jenny Powers

PARIS -- September 18, 2018 -- Adding methotrexate to adalimumab increased the response in patients with psoriasis who demonstrated a previous suboptimal response to adalimumab monotherapy, according to results of a single-arm, open-label, longitudinal study of 46 patients presented here at the 27th Congress of the European Academy of Dermatology and Venereology (EADV).

“The concomitant administration of an immunosuppressant such as methotrexate is an alternative to dose escalation as a response to treatment failure with tumour necrosis factor,” explained Kim Alexander Papp, MD, K. Papp Clinical Research, Probity Medical Research, Inc., Waterloo, Ontario, on September 14.

Patient quality of life and satisfaction also improved as the response to treatment increased. The proportion of patients achieving the coprimary endpoints of patient- and investigator-assessed satisfaction with therapy increased from 47.8% (patient) and 43.5% (investigator) at week 8 to 47.8% and 50.0% at week 16 and 54.3% and 56.5% at week 24, respectively. The proportion of patients achieving a Dermatology Life Quality Index (DLQI) response of 0 or 1 improved from 19.6% at week 8 to 37.0% at week 16, which was maintained until week 24 (end of study). The change from baseline in DLQI response was statistically significant at weeks 8, 16, and 24 (P

The proportion of patients achieving a Psoriasis Area Severity Index (PASI) score indicating complete clearance (PASI 100) was 13.0% at week 8, 10.9% at week 16, and 26.1% at week 24. The investigators observed a significant change from baseline in PASI score at weeks 8, 16, and 24 (P

The proportion of patients achieving a Physicians Global Assessment (PGA) response of “clear” or “minimal” increased from 26.1% at week 8 to 32.6% at week 16 and 43.5% at week 24.

“Reflecting the most recent Canadian psoriasis treatment guidelines, which emphasize patient-centred care, this study included subject and investigator satisfaction with therapy as a primary endpoint, in addition to quality-of-life assessments and traditional measures of response,” Dr. Papp stated.

Patients in this study had not shown an optimal response to adalimumab monotherapy or failed to maintain optimal response. All had PGA scores of ≥3 and PASI scores of ≥5.

Patients self-administered adalimumab every other week and took oral methotrexate at 7.5 to 25 mg weekly for 24 weeks.

Most patients were men (76.1%) and white (76.1%), and patients had a mean age (standard deviation) of 46.5 (±12.20) years. The median duration of psoriasis was 20.17 (range, 4.9-43.0) years. Psoriatic arthritis was reported in 39.1% of patients for a median duration of 9.74 (range, 0.8-38.7) years.

“Although traditional systemic therapies such as methotrexate can be effective in treating psoriasis, they have some concerns that limit use and require extensive laboratory monitoring,” Dr. Papp cautioned.

Measurements of serum adalimumab concentrations were taken at baseline and over the treatment course. These measurements revealed that the increased response in PASI scores, DLQI, and patient satisfaction were associated with increased serum concentrations of adalimumab that occurred after the combination therapy.

“Compliance with both adalimumab and methotrexate was ~97% during the study,” Dr. Papp noted.

Four serious adverse events occurred in 1 patient (2.2%), ie, cardiac arrest, generalised tonic-clonic seizure, loss of consciousness, and hypercapnia, but were considered unrelated to treatment by the investigator.

“While efficacy was noticeable at week 8, the endpoints used in this study showed continued improvements at weeks 16 and 24 that suggest a continuous benefit with the combination therapy over time,” Dr. Papp concluded.

[Presentation title: Adding Methotrexate to Adalimumab Therapy Improved Treatment Efficacy and Quality of Life in Psoriasis Patients. Abstract P1857]