Updated "User's Guide" Published for Anti-TNFs in IBD

Anti—tumor necrosis factor (TNF) drugs have been used for the treatment of inflammatory bowel disease (IBD) for 20 years. Studies of both originator and biosimilar versions of infliximab and other anti-TNFs have yielded advances in treatment, and in a review, a group of Swiss and Israeli authors have encapsulated this knowledge to provide what they called a user’s guide.

TNF inhibitors have been “the mainstay in the treatment of inflammatory bowel disease (IBD),” the authors said. Infliximab (Remicade) was the first anti-TNF biologic available to treat Crohn disease (CD) in 1998 and ulcerative colitis (UC) in 2005. In addition to infliximab, adalimumab is used in treatment of CD and UC, plus certolizumab pegol for CD and golimumab for UC. Focusing mainly on infliximab, for which the greatest body of evidence exists, the authors provided what they consider to be the most up-to-date methodology for addressing IBD with anti-TNFs.

Outlining the recommended indications for anti-TNF therapy in CD and UC, the authors noted there has recently been a shift toward introducing these drugs early when treating patients with serious disease. They cited research suggesting initiation of anti-TNF therapy during the first 2 years of CD may be more efficacious than initiating later in the course of the disease.

Investivative studies suggest combination therapy with immunomodulators has superior efficacy compared with anti-TNF agents alone, they said, and noted a greater risk of infection and neoplasms, or cancers, has been associated with combination therapy. The cancers include lymphoma and nonmelanoma skin cancer. This prompted the authors to conclude “The benefits of combination therapy should be balanced with its decreased safety profile.”

The authors also discussed reasons for withholding anti-TNF agents, prescreening guidelines, and recommendations for preventing infection. They recommended a full screening prior to the initiation of biologic agents for IBD.

In their discussion of infliximab infusion protocols, the authors noted that subcutaneous infliximab may soon be available, saying “a phase 1 study in the CD population has been recently conducted” on a subcutaneous formulation of the infliximab biosimilar CT-P13 (Remsima; Inflectra). Subcutaneous CT-P13 was recently approved in the European Union for all indications of intravenous infliximab in adult patients.

With respect to safety and the management of adverse effects, the authors acknowledged the “increased risk of infection” associated with anti-TNF therapy, the most common being pneumonia, which they said highlights the importance of immunization. They noted a 13-year follow-up study that showed a relative risk of serious infection of 2.46 (95% CI, 1.80-3.36) in patients who received infliximab. Risk factors for serious infection include prednisone and narcotic use, duration and severity of disease, and infliximab use, but not age, they said.

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Their recommendations for reducing the risk of malignancy in patients on anti-TNF therapy for IBD include annual skin exams and limiting the duration of combination therapy with thiopurines, which control inflammation, to less than 2 years. ” If the patient has a diagnosis of malignancy during TNF inhibitor therapy, the situation should be discussed by a multidisciplinary team of clinicians, they advised.

One of the limitations of therapy with TNFs in IBD is that there is a loss of response in as many as 30% to 50% of patients. The authors recommended therapeutic drug monitoring (TDM) to optimize dosing, suggesting TDM could “determine if the loss of response is due to subtherapeutic levels.” They wrote TDM may also be useful when a patient is in remission, either to prevent a flare or loss of response.

In their discussion of biosimilars in IBD, the authors concluded that switching from the infliximab originator product to the CT-P13 biosimilar is "equivalent to continuing [infliximab] originator for IBD patients,” based on the evidence. However, the “IBD-specific literature is lacking” for the infliximab biosimilar SB2 (Renflexis) and adalimumab biosimilars.

Reference

Vulliemoz M, Brand S, Juillerat P, Mottet C, Ben-Horin S, Michetti P. TNF-alpha blockers in inflammatory bowel diseases: practical recommendations and a user's guide: an update. Digestion. Published online July 31. doi:10.1159/000506898