Abstract
Background: Perianal fistulising Crohn’s disease (pfCD) is a challenging phenotype that markedly affects quality of life. Anti-TNF therapy, particularly infliximab, is commonly used first-line, yet primary non-response and secondary loss of response remain frequent. Adalimumab is often used second-line despite limited evidence. This study evaluated realworld outcomes of first- versus second-line adalimumab in pfCD to inform therapeutic sequencing.
Methods: A multicentre retrospective cohort study included adult pfCD patients treated between 2005 and 2024. The primary outcome compared adalimumab second-line (after infliximab) versus first-line using changes in the Perianal Disease Activity Index (PDAI). Secondary outcomes were hospitalisation and antibiotic use. Response was assessed at early (£24 weeks) and late (>24 weeks) time points. Analyses used Mann–Whitney U for continuous and Fisher’s exact for categorical variables.
Results: Of 167 patients, 107 received adalimumab first-line and 60 second-line. Among those previously exposed to infliximab, 45% stopped due to loss of response after initial response, 16% had non-response despite adequate levels, 25% ceased due to intolerance or adverse effects, and 11% due to patient preference. Second-line patients were older, had higher BMI, fewer smokers, and more stricturing disease, with similar immunomodulator use. PDAI pain improvement was greater with firstline therapy early (46% vs 4%, p<0.01) but not late (50% vs 9%, p=0.07). Hospitalisations, including for surgical management, were higher second-line (13% vs 11%, p=0.04) at >24 weeks. No differences were observed in PDAI discharge sub scores, clinical healing or response, or antibiotic use. More first-line patients remained on adalimumab (77% vs 28%, p<0.01) over follow-up (median 82 months, IQR 73), although treatment duration before cessation was similar (40 vs 40 months, p=0.47). Dose escalation was comparable (54% vs 37%, p=0.71). The distinction between true non-response and secondary loss of response was limited by the absence of pharmacokinetic data and incomplete documentation.
Conclusion: In pfCD, first-line adalimumab delivers greater improvements in PDAI pain sub scores and fewer hospitalisations on late outcomes assessment compared with second-line use. Adalimumab is effective after infliximab failure despite its similar mechanism of action, positioning it as a viable second-line option. Future studies incorporating standardised clinical and patient-reported outcome measures with radiological endpoints are needed to refine therapeutic sequencing in this high-risk population.