Background: In patients with inflammatory bowel disease (IBD) the addition of an immunosuppressant (IM) after loss of response to anti-TNF alpha monotherapy is regarded as an emerging strategy of therapeutic optimization. However, few clinical data have been reported to date. The aim of this study was to evaluate efficacy and tolerability of this selective combination therapy in patients with IBD.
Methods: All consecutive patients with loss of response to anti-TNF alpha monotherapy despite an intensive dose optimization who added an IM from October 2014 to October 2016 were entered in a prospectively maintained database. The steroid-free remission and the clinical response, this latter defined as a clinical improvement (reduction of Harvey-Bradshaw Index ≥3 for Crohn's disease and of Mayo Partial Score ≥2 for ulcerative colitis compared with baseline) with a concomitant reduction of steroid dosage compared with baseline and discontinuation within twelve weeks, were set as clinical end points.
Results: Among 630 patients treated with biologics during the study period, 46 (33 Crohn's disease and 13 ulcerative colitis) were included. A total of 31 patients (67.4%) were treated with an intravenous anti-TNFα (infliximab, as originator product or biosimilar), while 15 (32.6%) with a subcutaneous anti-TNFα agent (10 adalimumab and 5 golimumab). The mean doses of thiopurines used in combination therapy were below those regarded as therapeutic in IBD, methotrexate was mostly employed at a dose of 15 mg/week, and all patients treated with mycophenolate mofetil were able to tolerate the target dose of 1500 mg/day. The mean duration of total follow-up was 12.8±7.3 months. Twenty-one patients (45.7%) remained on combination therapy at the end of follow-up: 15 (32.6%) maintained a steroid-free remission, and 6 patients (13.0%) achieved a clinical response. In patients who experienced a treatment success, mean value of C-reactive protein sharply decreased from the baseline (16.6±25.6 mg/L, normal values <5 mg/L) to the following months and at the end of follow-up (5.6±6.1 mg/L, p=0.01 compared with baseline; figure 1). Adverse events leading to treatment discontinuation were reported in 7 out of 46 (15.2%) patients.
Conclusions: In patients with IBD the addition of an immunosuppressant is an effective and safe optimization strategy after loss of response to anti-TNF alpha monotherapy. Low doses of IM are sufficient to achieve a clinical response in this setting.