P2186 - Improved IBD Clinical Outcomes Using Combination Therapy With Infliximab and Immunomodulator Compared to Monotherapy with Infliximab Alone: A Comprehensive Meta-Analysis
North Shore-Long Island Jewish, Northwell Manhasset, NY
Jeffrey Lowell, MD, PhD1, Keith S. Sultan, MD2 1North Shore-Long Island Jewish, Northwell, Manhasset, NY; 2Northwell Health, Great Neck, NY
Introduction: Infliximab (IFX) is highly effective for the treatment of inflammatory bowel disease (IBD) but primary non-response and secondary loss-of-response is common due to anti-drug antibody (ADA) development that reduces biologically active IFX. The landmark SONIC trial showed combination therapy (CT) with IFX and immunomodulator (IMM) azathioprine (AZA) reduced ADA development, increased IFX troughs, and improved outcomes. Other trials and retrospective studies have since further supported the benefit of combining IFX with AZA, as well as other IMMs including mercaptopurine and methotrexate. Guidelines recommend CT over monotherapy (MT) with IFX alone, but utilization of CT remains suboptimal. With newer data published since SONIC, our goal was to provide an updated systematic review and meta-analysis on the use of CT.
Methods: A systematic review of PubMed through 6/1/2023 was conducted inclusive of cohort studies and randomized trials of adult patients naïve or previously exposed to IFX or IMMs. Extracted outcome measures included odds ratios (OR) and mean differences of clinical remission, ADA positivity, and IFX troughs, combined in a meta-analysis via log-OR transformation for pooled effect size estimation in a random-effects model with I-squared heterogeneity assessment. A priori subgroup analyses were performed to evaluate study-level differences among Crohn disease (CD), Ulcerative Colitis (UC), and IBD populations.
Results: Across 61 studies there were 4,309 CT patients and 4,239 MT patients. Analysis demonstrated that CT provides enhanced rates of induction and maintenance of clinical remission (OR 1.89, 95% confidence interval [CI] 1.56-2.28, p< 0.001), decreased ADA formation (OR 0.20, 95%CI 0.13-0.30, p< 0.001), and increased IFX trough levels (average mean difference +2.41 µg/mL, 95%CI 0.85-3.98) above therapeutic threshold (OR 2.52, 95%CI 1.76-3.61, p< 0.001). See Figures 1, 2, 3. These findings are consistent across subgroup analysis of studies of CD, UC, and IBD evaluated collectively.
Discussion: The present meta-analysis is the largest synthesis to date of clinical trial and real-world patient data evaluating CT of IFX and IMM versus MT for IBD. These results further support that CT improves clinical and pharmacokinetic outcomes over MT with IFX alone in IBD populations. Though the number and diversity of treatment options for IBD patients have expanded in recent years, optimal choices are still limited and IFX remains the staple treatment for improving patient outcomes.
Figure: Figures 1, 2, 3. Forest plots for pooled summary estimates of clinical remission (Fig. 1), anti-drug antibody (ADA) formation (Fig. 2), and infliximab (IFX) trough levels (Fig. 3) compared between studies of patients receiving combination therapy (IFX and immunomodulator) versus monotherapy (IFX alone). Data for individual studies analyzed as log-odds ratio (OR) transformed values but displayed as ORs to facilitate interpretation of study outcome. Studies marked with the obelus (†) indicate those in which data was extracted as a continuous variable (concentration ADA or IFX trough level) and displayed numerically within the original continuous variable context but visualized in the forest plot and analyzed within the meta-analysis as a log-OR transformed value consistent with the remaining studies. Data is displayed as OR and 95% confidence interval. Statistical details including tests for heterogeneity (I-squared) and overall effect (z-score) are provided within each figure. Each pooled effect was measured via random-effects model. Middle vertical dashed lines indicate an OR value of 1, or the value indicating no therapeutic preference for combination therapy versus monotherapy. Abbreviations: DZ, disease. Rem, remission. CD, Crohn disease. UC, ulcerative colitis. IBD, inflammatory bowel disease.
Disclosures:
Jeffrey Lowell indicated no relevant financial relationships.
Keith Sultan indicated no relevant financial relationships.
Jeffrey Lowell, MD, PhD1, Keith S. Sultan, MD2. P2186 - Improved IBD Clinical Outcomes Using Combination Therapy With Infliximab and Immunomodulator Compared to Monotherapy with Infliximab Alone: A Comprehensive Meta-Analysis, ACG 2023 Annual Scientific Meeting Abstracts. Vancouver, BC, Canada: American College of Gastroenterology.
