Background: Data on de-escalation of adalimumab (ADM) therapy in patients with Crohn's disease (CD) in clinical remission are scarce. However, dose de-escalation may not only have beneficial economic consequences, it might also decrease adverse events (AE). In this retrospective study, the outcome of dose de-escalation to ADM 40 mg every three weeks (ETW) in patients with CD was studied.
Methods: Out of 703 patients treated with ADM for CD in a tertiary referral center, we selected all patients who had received maintenance therapy with ADM 40 mg ETW with serum levels (SL) available before and after dose de-escalation. A sex- and age-matched control group consisted of patients continuing ADM 40mg EOW. ADM SL were measured using RIDASCREEN® In addition, patient reported outcome (PRO2), C-reactive protein (CRP) and serum albumin were collected. Other baseline variables included disease behavior, disease location, smoking behavior, concomitant therapy, bodyweight, and body mass index. ROC curve analyses were performed to define cut off values for continuous variables. Mann-Whitney U, Wilcoxon Signed Rank test, and Cox regression were performed using SPSS 23.0
Results: We identified 40 patients (11 male, median age 37 years) who dose de-escalated to ADM 40 mg ETW for ADM-related AE (n=1), ADM SL >7μg/mL (n=8), or both (n=31). Compared to the control population, ADM SL dropped significantly within four months, but without associated clinical or biochemical changes.
During a median follow-up of 24 months, 65% of patients maintained clinical response, but 35% needed dose escalation back to ADM 40mg EOW because of clinical relapse (n=8), ADM SL dropping to <4μg/mL (n=2), or both (n=4). CRP <3.5mg/L at dose de-escalation was independently associated with dose escalation free survival [Odds ratio 6.28 (95% CI 1.83–21.59), p=0.004]. We could not define a minimal ADM SL to consider or maintain dose de-escalation. In 53% of 32 patients with AE dose de-escalation was associated with a complete disappearance of AE after a median of 4 months (8/15 skin manifestation, 3/7 arthralgia, 5/7 frequent infectious episodes).
Conclusions: In this retrospective cohort analysis, 65% of patients were able to continue ADM therapy at a dose of 40 mg ETW for a median of 24 months. In half of the patients who experienced ADM related AE at baseline, the AE disappeared completely. Regardless of ADM serum levels, disease remission should be objectively assessed prior to dose de-escalation, since an elevated baseline CRP predicted clinical relapse and dose escalation back to 40mg EOW.