Using biologic therapies as first-line systemic treatment for psoriasis: A cohort study following the target trial emulation framework from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR).

BACKGROUND

Current treatment pathways for moderate-to-severe psoriasis in the United Kingdom and the Republic of Ireland direct initiation of targeted biologic immunomodulators when conventional systemic drugs are ineffective or not tolerated. Starting biologics early in the treatment pathway may modify the disease course and improve short- and long-term outcomes.

OBJECTIVE

To compare the effectiveness and risk of incident comorbid conditions over five years between initiating a biologic as the first systemic treatment and the standard-of-care (beginning with conventional non-biologic systemic therapy with possible subsequent switch to biologics).

METHODS

This study applied the target trial emulation framework using data from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) from September 2007 to December 2024. Adults (≥18 years) with moderate-to-severe psoriasis (baseline Psoriasis Area and Severity Index [PASI] ≥10) and no prior systemic therapy were included. Five-year trajectories of PASI and Dermatology Life Quality Index (DLQI) were modelled using mixed-effects repeated-measures models (MMRM). The probability of complete skin clearance (PASI = 0) and the risk of developing long-term comorbidities (cardiovascular, hepatic, neoplastic, metabolic, mental health, musculoskeletal disorder conditions, and incident psoriatic arthritis) were estimated using marginal structural models with stabilised inverse probability weighting to adjust for baseline and time-varying confounding.

RESULTS

We included 3,702 patients, 3,368 followed standard-of-care, and 334 initiated a biologic as first-line systemic therapy. At 5 years, mean PASI from MMRM was 4.7 (95% confidence interval [CI] 4.0-5.4) for standard-of-care and 2.0 (1.2-2.7) for biologic initiators; DLQI was 5.6 (4.2-7.0) and 3.5 (1.3-5.7), respectively. Cumulative rate of achieving PASI 0 was 32.2% versus 58.6%, with higher likelihood of PASI 0 for biologic initiators (hazard ratio [HR] 2.85, 95% CI 2.34-3.47). The cumulative risk of chronic comorbidities was lower among biologic initiators (47.5% vs 54.3%; HR 0.72, 95% CI 0.58-0.89), with lower risks of mental disorders (HR 0.64, 95%CI 0.44-0.94) and hepatic disorders (HR 0.54, 95%CI 0.38-0.76).

CONCLUSION

Initiating biologics as the first systemic therapy was associated with better clinical outcomes compared with standard stepwise approaches. These results support reconsideration of existing pathways to allow earlier use of biologics.