Background: Adalimumab (ADM) is efficacious in inducing and maintaining remission in ulcerative colitis (UC). Randomized trials show dose escalation from 40 mg every other week (EOW) to 40 mg every week (EW) in up to 20–25% within 1 year. Real life data show higher escalation rates and attempts for dose de-escalation in UC have not been described. This study aimed to assess the need for, the outcome of, and predictors of dose escalation and de-escalation in a large cohort of UC patients (pts) treated with ADM.
Methods: A detailed retrospective chart review was performed on consecutive pts from 10 Belgian centres that initiated ADM treatment for active UC, including pts demographics, disease characteristics, previous and concomitant medication including prior infliximab (IFX) use and the reason for discontinuation. Primary clinical benefit was based on physician global assessment (PGA) and no rectal bleeding at week 10. Success of dose-escalation was defined based on a positive PGA and absence of rectal bleeding on two consecutive visits at least 3 months apart. Persistent use of ADM 40mg EOW for ≥6 months after dose de-escalation, defined success of dose de-escalation. Variables associated with a primary clinical benefit of ADM, success of dose escalation and success of dose de-escalation were identified using Cox regression and backward Wald multivariate analysis.
Results: We included 231 pts [67% male, median (IQR) age at diagnosis 30.6 (22.9–44.8) years, median disease duration at start of ADM 5.5 (2.6–11.8) years, 63% previously exposed to infliximab (IFX)]. A primary clinical benefit was achieved in 101 pts (44%) and was less frequent in pts previously failing IFX [37% vs. 50%, OR 0.51 (95% CI 0.28–0.95), p=0.035]. 164 pts (71%) needed ADM discontinuation (N=56) or dose escalation (N=129) after a median of 2.8 (1.7–5.1) months (Fig 1). Disease duration <5 years [1.72 (1.25–2.33), p=0.001]; IFX discontinuation for primary non-response or loss of response [1.41 (1.03–1.93), p=0.032] and absence of primary clinical benefit [3.33 (2.38–4.76), p<0.001] were independently associated with ADM discontinuation or dose escalation. Dose escalation was successful in 77/129 (60%). Only primary response independently predicted successful dose escalation [3.08 (1.46–6.49), p=0.003]. Dose de-escalation was attempted in 71% (55/77) and was successful in 80%, but no predictive markers could be identified.
Conclusions: ADM is efficacious in UC, but an individualized therapy including dose escalation is often mandatory, being successful in the majority of patients