Methotrexate Adds No Benefit to Adalimumab in Psoriasis Treatment, Study Suggests

Adding methotrexate to adalimumab does not improve treatment effectiveness or durability in adults with plaque psoriasis, according to a study.¹ Findings suggest that adalimumab monotherapy performs similarly to combination therapy, with no meaningful differences in drug survival, Psoriasis Area Severity Index (PASI) 75 response, or adverse events.

Target trial emulation study finds no added effectiveness or persistence with combination therapy for plaque psoriasis. | Image credit: luchschenF - stock.adobe.com

This target trial emulsion cohort study is published in JAMA Dermatology.

“We found a lower mean [antidrug antibody] level with the use of concomitant methotrexate, indicating that the doses of methotrexate used on average were sufficient to induce a reduction in immunogenicity to adalimumab, which is the biological mechanism through which methotrexate is thought to prolong adalimumab persistence,” wrote the researchers of the study.

The study used real-world data from the British Association of Dermatologists Biologics and Immunomodulators Register collected between 2007 and 2021. Adults with plaque psoriasis who initiated adalimumab either as monotherapy or in combination with methotrexate were included. Methotrexate dosing was determined by the treating clinician.

The primary outcome was adalimumab drug survival at 1 year, with secondary outcomes including survival at 3 years, PASI75 responses at 1 and 3 years, serious adverse events, adalimumab concentrations, and antidrug antibody levels.

Methotrexate is used to treat patients with inflammatory conditions, such as arthritis and psoriasis.² Previously, combining methotrexate and adalimumab has been found to be more effective than adalimumab alone in patients with rheumatoid arthritis.³

A total of 231 participants receiving adalimumab with methotrexate and 1553 receiving adalimumab monotherapy were included in the cohort.¹ At 1 year, drug survival was 79.1% (95% CI, 71.8% to 87.2%) in the combination group and 78.1% (95% CI, 76.1% to 80.2%) in the monotherapy group, with no evidence of difference (1.0%; 95% CI, -7.0% to 8.9%). PASI75 response rates at 1 year were 49.4% (95% CI, 31.5% to 67.3%) for the combination group and 52.0% (95% CI, 47.7% to 56.3%) with no evidence of difference (-2.5%; 95% CI, -21.0% to 15.9%).

At 3 years, PASI75 rates were 37.2% (95% CI, 16.8% to 57.6%) vs 32.4% (95% CI, 28.0% to 36.8%), again with no significant difference (4.9%; 95% CI, -16.1% to 25.7%). Serious adverse events and adalimumab concentrations did not differ meaningfully between groups. However, the combination group showed significantly lower antidrug antibody levels (-123.7 AU/mL; 95% CI, -200.5 to -46.9), indicating reduced immunogenicity without a corresponding clinical benefit.

However, the researchers noted some limitations. First, there were high rates of treatment deviations and missing outcome data, particularly in PASI response and pharmacokinetic outcomes. Effect estimates for the intervention group were also less precise due to its smaller size. Additionally, quality of life measures could not be assessed due to substantial missing data, and pharmacokinetic results were limited by convenience sampling and timing inconsistencies.

Despite these limitations, the researchers believe the study suggests no evidence of clinical benefit by adding methotrexate to adalimumab as a combination therapy option for patients with plaque psoriasis.

“This target trial emulation cohort study did not find evidence that adding methotrexate to adalimumab was beneficial for treating plaque psoriasis,” wrote the researchers. “Future studies evaluating the effect of concomitant methotrexate should either focus on high (>10 mg/week) dosing regimens with biologics other than adalimumab for treating plaque psoriasis or with adalimumab for other inflammatory skin diseases.”

References

1. Yiu ZZN, Smith CH, Laws P, Hampton PJ, Griffiths CEM, Warren RB; BADBIR Study Group; BSTOP Study Group. Adalimumab monotherapy vs adalimumab with methotrexate for psoriasis. JAMA Dermatol. Published online June 4, 2025. doi:10.1001/jamadermatol.2025.1463

2. Methotrexate. Cleveland Clinic. Accessed June 16, 2025. https://my.clevelandclinic.org/health/drugs/20143-methotrexate

3. Heiberg MS, Rødevand E, Mikkelsen K, et al. Adalimumab and methotrexate is more effective than adalimumab alone in patients with established rheumatoid arthritis: results from a 6-month longitudinal, observational, multicentre study. Ann Rheum Dis. 2006 Oct;65(10):1379-1383. doi: 10.1136/ard.2006.051540