The use of combination biological or small molecule therapy in inflammatory bowel disease: A retrospective cohort study

Abstract

ObjectiveThere are limited data on using more than one biologic or small molecule drug combined to treat patients with inflammatory bowel disease. The aim of our study was to determine the effectiveness and safety of combination biologic use in inflammatory bowel disease.MethodsWe identified patients with Crohn's disease or ulcerative colitis who received treatment with a combination of two biologics or a biologic and a small molecule drug from 2015 to 2019 for persistent disease activity or concomitant rheumatological or dermatological disease. The primary end‐point was effectiveness, based on improvements in inflammatory markers, clinical, and endoscopic remission. The secondary end‐point was safety.ResultsOf the 50 patients treated with combination therapy there were significantly more patients in clinical and endoscopic remission at follow‐up compared to baseline (50% vs 14%, P = 0.0018, delta 36%, 95% confidence interval [CI] 0.13‐0.53; and 34% vs 6%, P = 0.0039, delta 28%, 95% CI 0.09‐0.47), respectively. Median erythrocyte sedimentation rate (17 mm/h vs 13 mm/h, P = 0.002) and C‐reactive protein (5.00 mg/dL vs 2.35 mg/dL, P = 0.002) also decreased posttreatment. There were eight serious adverse events and no deathsConclusionsCombination biologic therapy appears to be an effective option for patients with refractory inflammatory bowel disease or concomitant autoimmune disease that is inadequately controlled by biologic monotherapy. There was an increased risk of serious infection compared with biologic monotherapy; however, this risk might be minimized by discontinuing immunomodulators prior to initiating combination therapy. Large prospective studies are needed to confirm these findings.

Effectiveness and Safety of Combining Tofacitinib with a Biologic in Patients with Refractory Inflammatory Bowel Diseases

“…While there have been a number of recent reports using a combination of two biologics or a small molecule and a biologic in refractory IBD cases 5,6,8,[22][23][24] , most of these reports have been limited to DBT with only two case series and a case report reporting on TBT. 5,25,26 Glassner et al reported the overall effectiveness and safety of various combinatorial therapies in a cohort of 50 patients. 5 Although, they reported the rate of AEs among the 20 patients on TBT in their cohort, the effectiveness in this subgroup was not separately reported.…”

S0897 Efficacy and Safety of Combining Tofacitinib With a Biologic in Patients With Refractory Inflammatory Bowel Diseases

“…While there have been a number of recent reports using a combination of two biologics or a small molecule and a biologic in refractory IBD cases 5,6,8,[22][23][24] , most of these reports have been limited to DBT with only two case series and a case report reporting on TBT. 5,25,26 Glassner et al reported the overall effectiveness and safety of various combinatorial therapies in a cohort of 50 patients. 5 Although, they reported the rate of AEs among the 20 patients on TBT in their cohort, the effectiveness in this subgroup was not separately reported.…”

“…5,25,26 Glassner et al reported the overall effectiveness and safety of various combinatorial therapies in a cohort of 50 patients. 5 Although, they reported the rate of AEs among the 20 patients on TBT in their cohort, the effectiveness in this subgroup was not separately reported. Clark-Snustad et al reported the rate of AEs in 18 patients on TBT for refractory CD without separately reporting the effectiveness in this cohort.…”

“…4 However while the efficacy and safety of each individual biologics in IBD is well established, the efficacy and safety of a combinatorial therapy of two biologics or a small molecule and a biologic is yet to be shown in randomized control trials. Recently, there have been an increasing number of retrospective case series demonstrating that a dual biologic therapy (DBT) combining mechanistically different biologics may be a potential therapeutic option for refractory IBD patients, [5][6][7][8] there is however paucity of data on combination of biologic with a small molecule.…”

Tofacitinib Is Safe and Effective When Used in Combination With Infliximab for the Management of Refractory Ulcerative Colitis

“…Janus kinase inhibitors in UC targeting multiple inflammatory pathways may offer advantages over monoclonal antibodies targeting specific cytokines; 2 however, studies regarding the safety and effectiveness of combination biologic and small molecule therapies in UC are limited. 3,4 We herein describe the use of tofacitinib in combination with infliximab for the management of UC.…”