Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2025 Jul 1;161(7):731-738.
doi: 10.1001/jamadermatol.2025.1463.

Adalimumab Monotherapy vs Adalimumab With Methotrexate for Psoriasis

Zenas Z N Yiu  1   2 , Catherine H Smith  3 , Philip Laws  4 , Philip J Hampton  5 , Christopher E M Griffiths  1   3   6 , Richard B Warren  1   2 ; BADBIR Study Group; BSTOP Study Group
Affiliations
Randomized Controlled Trial

Adalimumab Monotherapy vs Adalimumab With Methotrexate for Psoriasis

Zenas Z N Yiu et al. JAMA Dermatol. .

Abstract

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.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Smith reported grants from MRC during the conduct of the study as well as grants from the European Commission outside the submitted work. Dr Laws reported personal fees from AbbVie, Sanofi, Lilly, Johnson and Johnson, Leo Pharma, Almirall, Galderma, Novartis, UCB, and Pfizer outside the submitted work. Dr Griffiths reported personal fees from AbbVie during the conduct of the study as well as grants from Almirall; personal fees from Artax, Boehringer Ingelheim, Bristol Meyers Squibb, Johnson and Johnson, Novartis, UCB Pharma, Lilly, Sun Pharma, and Boots UK; travel support from Anryt Pharma; and being the director of Global Psoriasis Atlas outside the submitted work. Dr Warren reported grants from AbbVie, Almirall, Amgen, Celgene, Janssen, Lilly, Leo Pharma, Novartis, Pfizer, and UCB during the conduct of the study as well as personal fees from AbbVie, Almirall, Amgen, Arena, Astellas, Avillion, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, DiCE, Galderma, GSK, Janssen, Lilly, Leo Pharma, Meiji Pharma, Novartis, Pfizer, RAPT Pharmaceuticals, Sanofi, Sun Pharma, UCB, and Union Therapeutics outside the submitted work. No other disclosures were reported.

References

    1. Yiu ZZN, Becher G, Kirby B, et al. ; BADBIR Study Group . Drug survival associated with effectiveness and safety of treatment with guselkumab, ixekizumab, secukinumab, ustekinumab, and adalimumab in patients with psoriasis. JAMA Dermatol. 2022;158(10):1131-1141. doi: 10.1001/jamadermatol.2022.2909 - DOI - PMC - PubMed
    1. Sbidian E, Chaimani A, Garcia-Doval I, et al. Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis. Cochrane Database Syst Rev. 2022;5(5):CD011535. doi: 10.1002/14651858.CD011535.pub5 - DOI - PMC - PubMed
    1. Hsu L, Snodgrass BT, Armstrong AW. Antidrug antibodies in psoriasis: a systematic review. Br J Dermatol. 2014;170(2):261-273. doi: 10.1111/bjd.12654 - DOI - PubMed
    1. Wilkinson N, Tsakok T, Dand N, et al. ; BSTOP Study Group; PSORT Consortium . Defining the therapeutic range for adalimumab and predicting response in psoriasis: a multicenter prospective observational cohort study. J Invest Dermatol. 2019;139(1):115-123. doi: 10.1016/j.jid.2018.07.028 - DOI - PMC - PubMed
    1. Tsakok T, Rispens T, Spuls P, Nast A, Smith C, Reich K. Immunogenicity of biologic therapies in psoriasis: myths, facts and a suggested approach. J Eur Acad Dermatol Venereol. 2021;35(2):329-337. doi: 10.1111/jdv.16980 - DOI - PubMed

Publication types