Waseem Ahmed1, Jonathan Galati2, Anand Kumar3, Paul J Christos4, Randy Longman1, Dana J Lukin1, Ellen Scherl1, Robert Battat5. 1. Jill Roberts Center for Inflammatory Bowel Disease, Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medical College, New York, New York. 2. Department of Medicine, New York University School of Medicine, New York, New York. 3. Jill Roberts Center for Inflammatory Bowel Disease, Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medical College, New York, New York; Division of Gastroenterology and Hepatology, Department of Medicine, Lenox Hill Hospital, New York, New York. 4. Division of Biostatistics, Department of Population Health Sciences, Weill Cornell Medical College, New York, New York. 5. Jill Roberts Center for Inflammatory Bowel Disease, Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medical College, New York, New York. Electronic address: rob9175@med.cornell.edu.
Abstract
BACKGROUND AND AIMS: We conducted a systematic review and meta-analysis to summarize emerging data on the safety and effectiveness of dual biologic therapy in combination or with tofacitinib in patients with refractory inflammatory bowel disease (IBD). METHODS: Through a systematic search of multiple electronic databases through November 9, 2020, we identified cohort studies or case series (>10 patients) reporting the safety and effectiveness of simultaneous use of biologic agents in combination or with tofacitinib in patients with IBD. Rates of adverse events, clinical remission, and endoscopic remission were synthesized using pooled data, and we identified factors associated with successful dual therapy. RESULTS: We identified 30 studies reporting 288 trials of dual biologic or small molecule therapy in 279 patients (76% Crohn's disease; median duration of treatment 24 weeks (IQR25-IQR75 1332)). The main indications for dual therapy included medically refractory IBD (81%) and concurrent extra-intestinal manifestations or rheumatologic disease (12%). The most common combinations of dual therapy included tumor necrosis factor-α antagonists & anti-integrins (48%), ustekinumab & anti-integrins (19%); 61% of patients had previously failed at least one of the two therapies used in combination. Over a median follow-up of 32 weeks (IQR25-IQR75 24-52), pooled rates of adverse and serious adverse events were 31% (95% CI, 13%-54%) and 6.5% (95% CI, 2.1%-13.1%); pooled rates of clinical and endoscopic remission were 59% (95% CI, 42%-74%), and 34% (95% CI, 23%-46%), respectively. 12% (95% CI, 4%-24%) of patients required surgery. Rates of success were higher in patients on dual therapy due to EIM. Heterogeneity was not significant for endoscopic response (P = .88, I2 = 0%), endoscopic remission (P = .44, I2 = 0%), and malignancy (P = .87, I2 = 0%). However, significant heterogeneity existed for other outcomes. CONCLUSIONS: Dual biologic or small molecule therapy may be a possible option in highly selected, refractory IBD patients at specialized centers. Higher quality combination of therapies with a significant improvement in the quality of data is required prior to more widespread use.
BACKGROUND AND AIMS: We conducted a systematic review and meta-analysis to summarize emerging data on the safety and effectiveness of dual biologic therapy in combination or with tofacitinib in patients with refractory inflammatory bowel disease (IBD). METHODS: Through a systematic search of multiple electronic databases through November 9, 2020, we identified cohort studies or case series (>10 patients) reporting the safety and effectiveness of simultaneous use of biologic agents in combination or with tofacitinib in patients with IBD. Rates of adverse events, clinical remission, and endoscopic remission were synthesized using pooled data, and we identified factors associated with successful dual therapy. RESULTS: We identified 30 studies reporting 288 trials of dual biologic or small molecule therapy in 279 patients (76% Crohn's disease; median duration of treatment 24 weeks (IQR25-IQR75 1332)). The main indications for dual therapy included medically refractory IBD (81%) and concurrent extra-intestinal manifestations or rheumatologic disease (12%). The most common combinations of dual therapy included tumor necrosis factor-α antagonists & anti-integrins (48%), ustekinumab & anti-integrins (19%); 61% of patients had previously failed at least one of the two therapies used in combination. Over a median follow-up of 32 weeks (IQR25-IQR75 24-52), pooled rates of adverse and serious adverse events were 31% (95% CI, 13%-54%) and 6.5% (95% CI, 2.1%-13.1%); pooled rates of clinical and endoscopic remission were 59% (95% CI, 42%-74%), and 34% (95% CI, 23%-46%), respectively. 12% (95% CI, 4%-24%) of patients required surgery. Rates of success were higher in patients on dual therapy due to EIM. Heterogeneity was not significant for endoscopic response (P = .88, I2 = 0%), endoscopic remission (P = .44, I2 = 0%), and malignancy (P = .87, I2 = 0%). However, significant heterogeneity existed for other outcomes. CONCLUSIONS: Dual biologic or small molecule therapy may be a possible option in highly selected, refractory IBD patients at specialized centers. Higher quality combination of therapies with a significant improvement in the quality of data is required prior to more widespread use.
Authors: Quazim A Alayo; Marc Fenster; Osama Altayar; Kerri L Glassner; Ernesto Llano; Kindra Clark-Snustad; Anish Patel; Lukasz Kwapisz; Andres J Yarur; Benjamin L Cohen; Matthew A Ciorba; Deborah Thomas; Scott D Lee; Edward V Loftus; David I Fudman; Bincy P Abraham; Jean-Frederic Colombel; Parakkal Deepak Journal: Crohns Colitis 360 Date: 2022-02-10
Authors: Laurent Goessens; Jean-Frédéric Colombel; An Outtier; Marc Ferrante; Joao Sabino; Ciaran Judge; Reza Saeidi; Louise Rabbitt; Alessandro Armuzzi; Eugeni Domenech; George Michalopoulos; Anneline Cremer; Francisco Javier García-Alonso; Tamas Molnar; Konstantinos Karmiris; Krisztina Gecse; Joep Van Oostrom; Mark Löwenberg; Klaudia Farkas; Raja Atreya; Davide Giuseppe Ribaldone; Christian Selinger; Frank Hoentjen; Benoit Bihin; Shaji Sebastian; Jean-François Rahier Journal: United European Gastroenterol J Date: 2021-10-25 Impact factor: 4.623