Systematic Review With Meta-analysis: Safety and Effectiveness of Combining Biologics and Small Molecules in Inflammatory Bowel Disease

Alayo, Quazim A.; Fenster, Marc; Altayar, Osama; Glassner, Kerri; Llano, Ernesto M.; Clark‐Snustad, Kindra; Patel, Anish; Kwapisz, Lukasz; Yarur, Andrés; Cohen, Benjamin L.; Ciorba, Matthew A.; Thomas, Deborah A.; Lee, Scott D.; Loftus, Edward V.; Fudman, David; Abraham, Bincy; Colombel, Jean Fréd́eric; Deepak, Parakkal

doi:10.1093/crocol/otac002

Cited by 38 publications

(50 citation statements)

References 50 publications

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“…Rates of adverse events were lower (5.7%) than those reported by other combination therapy studies and also lower than a real-world SBT safety study (15.7%) [17 ▪ ,18]. In a meta-analysis across 13 studies (one clinical trial, 12 observational studies) involving 266 patients on seven different combinations, Alayo et al [19 ▪▪ ] identified that the most common DBT and SBT were VDZ with anti-TNF ( n = 56) or Tofa ( n = 57), respectively. Pooled rates of serious adverse events for these were 9.6% [95% confidence interval (95% CI), 1.5–21.4] for VDZ+anti-TNF and 1.0% (95% CI, 0.0–7.6) for Tofa+VDZ.…”

Section: Treatment Strategiesmentioning

confidence: 75%

Management of refractory inflammatory bowel disease

Gergely¹,

Prado

Deepak³

2022

Current Opinion in Gastroenterology

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Purpose of reviewNearly one-third of patients with inflammatory bowel disease (IBD) do not achieve remission despite our best therapies. When this happens, it is critical to understand the reason for treatment failure. Once nonresponse is confirmed, these patients should be referred to an IBD centre for multidisciplinary care. This review will discuss the remaining treatment options, including escalation of biologics to unlicensed doses, combination biologics, nonvalidated therapies and surgical options. It will additionally provide updates in the management of acute severe ulcerative colitis (ASUC).Recent findingsThere is an increasing interest in combination biologics to treat refractory IBD, although data supporting its safety and effectiveness are limited. The use of hyperbaric oxygen, mesenchymal stem cell therapy and dietary interventions also show early promise in this area. Studies have additionally focused on personalized therapy to identify aggressive phenotypes and predict treatment response in these challenging patients. In ASUC, infliximab and cyclosporine remain mainstays of treatment, and tofacitinib shows promise as a salvage therapy.SummaryRefractory IBD is common, yet large knowledge gaps remain. Recent and ongoing studies have focused on medical, surgical and dietary approaches with mixed success. Larger prospective studies are desperately needed to address this complex issue.

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Section: Treatment Strategiesmentioning

confidence: 75%

Management of refractory inflammatory bowel disease

Gergely¹,

Prado

Deepak³

2022

Current Opinion in Gastroenterology

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“…In a recent meta-analysis (266 patients from 13 studies) most common combination therapy was with VDZ. The overall adverse events ranged from 0% to 12%, and pooled rates of adverse events were higher with VDZ and IFX combination compared to IFX and Tofacitinib (9.6% vs. 1%) [30]. VDZ is the commonly preferred agent in combination therapy because of its gut selectivity and favorable safety profile.…”

Section: Dual Biologic Therapymentioning

confidence: 99%

“…However, combination of biologics and/or small molecules appears to be effective in inducing clinical remission in this subset of patients. In a meta-analysis by Alayo et al [30], the pooled clinical remission rates in refractory IBD ranged from 40.5% to 80% and endoscopic remission ranged from 18% to 37% across various studies. In another meta-analysis the pooled rates of clinical and endoscopic remission were 59% (95% CI 42−74%), and 34% (95% CI 23−46%), respectively [32 ▪▪ ].…”

Section: Considerations When Choosing Appropriate Biological Therapymentioning

confidence: 99%

Considerations when starting patients on multiple biologics and small molecules

Vuyyuru

Kedia

Ahuja

2022

Current Opinion in Gastroenterology

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Purpose of reviewInflammatory bowel disease (IBD) is complex disease that poses significant economic, and psychological burden on patients. Despite advent of newer biologics and small molecules targeting different aspects of immunopathogenesis, there appears to be a plateau in clinical outcomes. In this review we discuss the role of multiple biologics, existing evidence and various considerations when prescribing multiple biologics.Recent findingsRecent scientific advances helped to unravel the pathophysiology of inflammatory bowel disease and newer cytokines have been identified which can be potential targets in the management of IBD. Targeting more than one cytokine appears to be logical solution to break the therapeutic ceiling to improve clinical outcomes in IBD. The combination biologics appear safe and effective; however, the available evidence is limited. Refractory IBD, presence of other immune mediated inflammatory diseases and extra intestinal manifestations are currently the common considerations of combination biologics in IBD.SummaryInflammatory bowel disease is a complex immune mediated disease with diverse clinical presentation and often has a complicated clinical course requiring multidisciplinary management. As the number of targeted therapies increases so does the concern on their safety and efficacy. Combination biologics though may appear to be safe, we need well designed prospective studies for firm conclusions.

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“…Indeed, this modality has seen great development in oncological or hematological treatments[ 14 ]. Similarly, in patients with rheumatologic pathologies, this approach is used in some patient subgroups[ 16 ]. This approach is also applicable to patients with refractory IBD to advanced treatments (dual therapy) by using two biologics simultaneously or a biologic in combination with a small molecule[ 16 , 17 ].…”

Section: Definition and Indications Of Dual Therapymentioning

confidence: 99%

“…Similarly, in patients with rheumatologic pathologies, this approach is used in some patient subgroups[ 16 ]. This approach is also applicable to patients with refractory IBD to advanced treatments (dual therapy) by using two biologics simultaneously or a biologic in combination with a small molecule[ 16 , 17 ]. In patients with IBD, there are two distinct scenarios in which it can be used: (1) Patients with refractory IBD without EIM; and (2) patients with IBD in remission, but with active EIM or immune-mediated inflammatory diseases (IMID)[ 18 ].…”

Section: Definition and Indications Of Dual Therapymentioning

confidence: 99%

Role of the combination of biologics and/or small molecules in the treatment of patients with inflammatory bowel disease

Balderramo¹

2022

World J Gastroenterol

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Inflammatory bowel disease (IBD) is a group of chronic diseases that includes ulcerative colitis, Crohn’s disease, and indeterminate colitis. Patients with IBD require prolonged treatment and high utilization of healthcare resources for proper management. The treatment of patients with IBD is focused on achieving therapeutic goals including clinical, biochemical, and endoscopic variables that result in improvement of the quality of life and prevention of disability. Advanced IBD treatment includes tumor necrosis factor inhibitors, integrin antagonist, antagonist of the p40 subunit of interleukin 12/23, and small molecule drugs. However, despite the multiple treatments available, about 40% of patients are refractory to therapy and present with persistent symptoms that have a great impact on their quality of life, with hospitalization and surgery being necessary in many cases. Dual therapy, a strategy sometimes applicable to refractory IBD patients, includes the combination of two biologics or a biologic in combination with a small molecule drug. There are two distinct scenarios in IBD patients in which this approach can be used: (1) Refractory active luminal disease without extraintestinal manifestations; and (2) patients with IBD in remission, but with active extraintestinal manifestations or immune-mediated inflammatory diseases. This review provides a summary of the results (clinical response and remission) of different combinations of advanced drugs in patients with IBD, both in adults and in the pediatric population. In addition, the safety profile of different combinations of dual therapy is analyzed. The use of newer combinations, including recently approved treatments, the application of new biomarkers and artificial intelligence, and clinical trials to establish effectiveness during long-term follow-up, are needed to establish new strategies for the use of advanced treatments in patients with refractory IBD.

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Systematic Review With Meta-analysis: Safety and Effectiveness of Combining Biologics and Small Molecules in Inflammatory Bowel Disease

Cited by 38 publications

References 50 publications

Management of refractory inflammatory bowel disease

Management of refractory inflammatory bowel disease

Considerations when starting patients on multiple biologics and small molecules

Role of the combination of biologics and/or small molecules in the treatment of patients with inflammatory bowel disease

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