Anti–Tumor Necrosis Factor-α Monotherapy Versus Combination Therapy with an Immunomodulator in IBD

Dulai, Parambir S.; Siegel, Corey A.; Peyrin–Biroulet, Laurent

doi:10.1016/j.gtc.2014.05.009

Cited by 20 publications

(22 citation statements)

References 74 publications

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“…Combination therapy is the best way to prevent the formation of antibodies,23 which are known to decrease efficacy and increase the risk of infusion reactions 24. However, the increasing use of combination therapy raises other concerns, such as a potential increase in serious treatment-emergent adverse events (eg, infections and malignant conditions) 25. We shall probably face the same problems with vedolizumab and ustekinumab, although gut specificity of the former might be associated with a better safety profile.…”

Section: Introductionmentioning

confidence: 99%

Next generation of small molecules in inflammatory bowel disease

Olivera

Danese

Peyrin–Biroulet

2016

Gut

Self Cite

137

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Section: Introductionmentioning

confidence: 99%

Next generation of small molecules in inflammatory bowel disease

Olivera

Danese

Peyrin–Biroulet

2016

Gut

Self Cite

137

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“…Within the phase III studies of vedolizumab in patients with UC, the rate of secondary loss of response was approximately 25%, and although concomitant immunosuppressive therapy was associated with a reduction in immunogenicity, it had no clear impact on vedolizumab efficacy or maintenance of efficacy . When evaluating TNF antagonists, subanalyses of randomized controlled trials stratified by immunosuppressive use similarly demonstrated a reduction in immunogenicity, with no clear benefit for combination therapy; however, further studies powered to adequately assess this question demonstrated a clear benefit for combination therapy over TNF antagonist monotherapy . Therefore, although this exploratory subanalysis failed to demonstrate a clinical benefit for immunosuppressive combination therapy with vedolizumab, combination therapy did protect against immunogenicity.…”

Section: Clinical Considerationsmentioning

confidence: 99%

Vedolizumab for the Treatment of Moderately to Severely Active Ulcerative Colitis

et al. 2015

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Ulcerative colitis is a chronic, idiopathic, inflammatory bowel disease characterized by a relapsing and remitting course. A substantial proportion of patients fail conventional therapies despite therapy with immunosuppressives and tumor necrosis factor antagonists. Accordingly, newer therapeutic agents that target disease-specific inflammation and minimize adverse events are required. Central to the pathogenesis of ulcerative colitis is an aberrant host response to commensal microorganisms with a resultant dysregulation of gut immune homeostasis and lymphocyte trafficking. Recently, a newer biologic, vedolizumab, which blocks lymphocyte trafficking, has been developed for use in moderate to severe ulcerative colitis. The efficacy of this agent has been demonstrated to be similar to that of other currently available biologics, and the selectivity of this agent in blocking lymphocyte migration to the gut has substantially reduced treatment-related adverse events. The drug has now been approved for use in the United States and Europe, and, although the exact positioning of this biologic in clinical practice is yet to be defined, it represents an important new chapter in our armamentarium of treatment options for this population. In this review, we will highlight key considerations to be made by providers when using this agent in clinical practice.

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“…Large trials have shown a benefit of combination therapy in the short-term in reducing immunogenicity to anti-TNF and achieving corticosteroid-free clinical remission. 3,6,8 LOR, however, is a common clinical problem in patients treated with anti-TNF. Overall, 45% of our cohort had primary non-response or secondary LOR over the follow-up period.…”

Section: Discussionmentioning

confidence: 99%

“…There has been conflicting evidence regarding the benefits of immunomodulator (IM) combination therapy versus anti‐tumour necrosis factor alpha (anti‐TNF) monoclonal antibody monotherapy in maintaining clinical and endoscopic remission in inflammatory bowel disease (IBD) patients . Immunogenicity is associated with anti‐TNF therapy, particularly with the chimeric infliximab (IFX) .…”

Section: Introductionmentioning

confidence: 99%

“…There has been conflicting evidence regarding the benefits of immunomodulator (IM) combination therapy versus anti-tumour necrosis factor alpha (anti-TNF) monoclonal antibody monotherapy in maintaining clinical and endoscopic remission in inflammatory bowel disease (IBD) patients. [1][2][3] Immunogenicity is associated with anti-TNF therapy, particularly with the chimeric infliximab (IFX). 4 There is evidence available that shows a reduction in this immunogenicity and formation of anti-TNF antibodies with combination therapy, although the exact mechanism is still not entirely understood.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Immunomodulator use does not prevent first loss of response to anti‐tumour necrosis factor alpha therapy in inflammatory bowel disease: long‐term outcomes in a real‐world cohort

Varma

Rajadurai

Holt

et al. 2019

Internal Medicine Journal

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Background Recent prospective studies suggest combination therapy with immunomodulators improves efficacy, but long‐term data is limited. Aim To assess whether anti‐tumour necrosis factor alpha (anti‐TNF) monotherapy was associated with earlier loss of response (LOR) than combination therapy in a real‐world cohort with long‐term follow up. Methods A retrospective audit was conducted of inflammatory bowel disease patients receiving anti‐TNF therapy in a tertiary centre and specialist private practices. All patients with accurate data for anti‐TNF commencement and adequate correspondence to determine end‐points were included. Outcomes measured included time to first LOR, causes and biochemical parameters. Results Two hundred and twenty‐four patients were identified; 139 (62.1%) on combination therapy and 85 (37.9%) on monotherapy. Forty‐five percent of patients had LOR during follow up until a maximum of 8.5 years; 59.4% on combination therapy and 40.6% on monotherapy (P = 0.533). The median time to LOR was not different between groups; 1069 days for combination therapy and 1489 days for monotherapy (P = 0.533). There was no difference in time to LOR between patients treated with different combination regimens or different anti‐TNF agents. Conclusion In this large cohort of patients in a real‐world setting, patients treated with anti‐TNF monotherapy had similar rates of LOR as patients on anti‐TNF combination therapy, at both short‐ and long‐term follow up.

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Anti–Tumor Necrosis Factor-α Monotherapy Versus Combination Therapy with an Immunomodulator in IBD

Cited by 20 publications

References 74 publications

Next generation of small molecules in inflammatory bowel disease

Next generation of small molecules in inflammatory bowel disease

Vedolizumab for the Treatment of Moderately to Severely Active Ulcerative Colitis

Immunomodulator use does not prevent first loss of response to anti‐tumour necrosis factor alpha therapy in inflammatory bowel disease: long‐term outcomes in a real‐world cohort

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