The Use of Combination Biologic or Small Molecule Therapy in Inflammatory Bowel Disease: A Retrospective Cohort Study

BACKGROUND: There is limited data on the use of more than one biologic or small molecule in the treatment of patients with inflammatory bowel disease (IBD). The aim of our study was to determine the effectiveness and safety of combining two or more biologics or a biologic and small molecule in patients with IBD.

METHODS: We collected data on 50 patients with Crohn’s disease (CD) or ulcerative colitis (UC) who received treatment with a combination of two biologics or a biologic and small molecule from 2015 to 2019 for persistent disease activity or concomitant rheumatologic or dermatologic disease. Combinations included vedolizumab (VDZ) with either ustekinumab (UST) (n = 25), adalimumab (ADA) (n = 3), certolizumab (CZP) (n = 2), golimumab (GOL) (n = 2), or tofacitinib (TOF) (n = 8); or TOF with either infliximab (IFX) (n = 4), GOL (n = 4), CZP (n = 1), or UST (n = 3); or ADA and apremilast (n = 1). There were 3 patients who received more than one combination during follow up for a total of 53 combinations in 50 patients. Clinical scoring and inflammatory markers (ESR, CRP, hemoglobin, and albumin) were collected within one month prior to starting combination therapy (baseline) and at follow up (after at least two months on combination therapy). Endoscopic data was collected within 6 months prior to initiation of combination therapy and at follow up (after at least two months on combination therapy). Adverse events were documented.

RESULTS: The mean age was 36.7 years, 68% were female, 76% Caucasian, with a disease duration of 14.8 years (2–48). Patients had failed therapy with an average of 2 previous biologic medications. There were significantly more patients in clinical and endoscopic remission at follow up, 50% vs 14%, P = 0.002, delta 33%; 95% CI 0.13–0.53, and 34% vs 6%, P = 0.004, delta 28%; 95% CI 0.09–0.47 respectively. The median ESR and CRP decreased, 17 vs 13, P = 0.002, and 5 vs 2.35, P = 0.002, respectively. The mean hemoglobin and albumin improved, 12.12 vs 12.6, P = 0.022, and 3.58 vs 3.79, P = 0.017. There were 8 serious adverse events (SAE), and no deaths. Of those with a SAE, 57% were on an immunomodulator compared to 17.4% of those without a SAE, P = 0.019.

CONCLUSION(S): Combination biologic therapy is an effective option for IBD patients with refractory disease or concomitant autoimmune disease inadequately controlled by biologic monotherapy. There appears to be an increased risk of serious infection compared to biologic monotherapy, however this risk may be minimized by discontinuing immunomodulators prior to initiation of combination therapy. Larger prospective studies are needed to confirm these findings.