Adalimumab Monotherapy vs Adalimumab With Methotrexate for Psoriasis.

IMPORTANCE

It is unclear whether concomitant methotrexate enhances the effectiveness and persistence of adalimumab for psoriasis. The recent OPTIMAP randomized clinical trial that tested adalimumab against adalimumab with methotrexate could not adequately answer this question due to underrecruitment.

OBJECTIVE

To determine the effectiveness of using methotrexate with adalimumab in people with plaque psoriasis.

DESIGN, SETTING, AND PARTICIPANTS: This target trial emulation cohort study replicated key aspects of the OPTIMAP trial design using the British Association of Dermatologists Biologics and Immunomodulators Register between 2007 and 2021.

EXPOSURES

Adalimumab, 40 mg, every other week monotherapy (comparator) vs adalimumab, 40 mg, every other week and methotrexate weekly, with the dosage as determined by the clinician (intervention).

MAIN OUTCOMES AND MEASURES

The primary outcome was the difference in the adalimumab survival function at 1 year. The secondary outcomes included differences in adalimumab survival function at 3 years; 75% reduction in Psoriasis Area and Severity Index (PASI75) at 1 year and 3 years; serious adverse events at 1 and 3 years; and adalimumab concentrations and antidrug antibodies at 1 year. Inverse probability treatment and censoring weighting were used for covariate and missing outcome adjustment. Flexible parametric survival models were fitted for survival outcomes and generalized linear models for other outcomes.

RESULTS

There were 231 and 1553 participants (754 female individuals [42.3%]) in the intervention (median [IQR] age, 43.7 [35.1-53.1] years) and comparator (median [IQR] age, 43.6 [34.2-52.0] years) arms, respectively. Drug survival for the comparator arm at 1 year was 78.1% (95% CI, 76.1%-80.2%) and the intervention arm was 79.1% (95% CI, 71.8%-87.2%), with no evidence of difference (1.0%; 95% CI, -7.0% to 8.9%). PASI75 at 1 year and 3 years in the comparator arm was 52.0% (95% CI, 47.7%-56.3%) and 32.4% (95% CI, 28.0%-36.8%), respectively; in the intervention arm, PASI75 was 49.4% (95% CI, 31.5%-67.3%) and 37.2% (95% CI, 16.8%-57.6%), respectively. There was no evidence of differences at 1 year and 3 years (-2.5%; 95% CI, -21.0% to 15.9% and 4.9%; 95% CI, -16.1% to 25.7%, respectively). There was no evidence for a difference between the 2 arms for serious adverse events and adalimumab concentrations, while the intervention arm had a lower antidrug antibody level (risk difference, -123.7 AU/mL; 95% CI, -200.5 to -46.9).

CONCLUSION AND RELEVANCE

The results of this cohort study suggest that there was no evidence of a difference in the effectiveness and persistence of adalimumab in people with psoriasis between monotherapy and adalimumab with concomitant methotrexate.