Delphi Consensus Outlines Anti-TNF Introduction, Monitoring Guidelines for Patients with IBD

Sandro Ardizzone, MD

Credit: Enthera Pharmaceuticals

Results from a Delphi consensus among inflammatory bowel disease (IBD) expert gastroenterologists are providing clinicians with everyday clinical practice guidance for introducing and monitoring anti-tumor necrosis factor (TNF) therapy in patients with IBD.

Expert opinions about the introduction, optimization, and maintenance of anti-TNF therapy were recorded and subject to participant feedback to produce a collective consensus for everyday clinical practice given the current lack of dedicated clinical trials to develop data-driven recommendations for the treatment.¹

“International guidelines for IBD are focused on which drug therapy should be used but lack precise indications about the correct timing of use. With the increase of real-life experience on the use of anti-TNF therapy, the questions about the timing of proper introduction, optimization and maintenance are becoming increasingly critical,” wrote investigators.¹

Although there is no cure for IBD, current treatment options including medications, surgery, and a range of diet and lifestyle changes seek to reduce inflammation and mitigate symptoms.² Anti-TNF therapy blocks the activity of TNF, a substance in the body causing inflammation and leading to immune system diseases like IBD.³ However, guidelines for introducing and monitoring anti-TNF therapy in patients with IBD are sparse.

To formulate temporary consensus recommendations for introducing and monitoring anti-TNF therapy in patients with IBD, Sandro Ardizzone, MD, head of the gastrointestinal unit at ASST Fatebenefratelli Sacco-University of Milan in Italy, and colleagues recorded expert opinions based on responses to 2 successive questionnaires about unaddressed issues regarding the use of anti-TNF therapy for IBD. Investigators invited 61 experts to participate in the first round, of which 52 (85.3%) responded and 9 (14.7%) did not. All participating experts were invited to the second round, of which 5 (9.6%) did not respond, and 47 took part (90.4%).¹

Opinions were recorded autonomously and independently through a questionnaire administered by an ad hoc software with individualized and password-protected access to ensure confidentiality. Participants voted on each statement and left comments voicing their knowledge and input. The group’s level of agreement was based on individual evaluations by each participant for each proposed statement.¹

The judgment was expressed on a Likert scale from 1-9, where 1 indicated maximum disagreement and 9 indicated maximum agreement. For the purpose of analysis, consensus for agreement was defined as >85% of respondents voting 7–9, weak consensus for agreement was defined as <85% of respondents voting 7–9 but >90% voting 4–9, and nonconsensus was defined as < 90% respondents voting 4–9 and 1–6.¹

Controlled feedback was implemented through repeated reviews. The questionnaire was reformulated after each phase to reflect the summary of the opinions originated in the prior round. It was then sent back to survey participants and subject to further dissemination to gradually produce a group consensus.¹

The first questionnaire included 19 statements, 11 of which achieved consensus for agreement. Weak consensus for agreement was observed for 5 statements, pertaining mainly to the optimization of anti-TNF therapy in patients with ulcerative colitis. An additional 3 statements received dispersed opinions, all regarding the maintenance of anti-TNF therapy for patients with Crohn disease and ulcerative colitis.¹

Investigators then excluded statements achieving consensus for agreement and weak consensus for agreement and adjusted the remaining statements for inclusion in the second questionnaire, which included a total of 6 statements. Consensus for agreement was achieved for a single statement regarding the optimization of anti-TNF therapy during maintenance. A pair of statements about the use of clinical and laboratoristic evaluation to indicate optimization and loss of response to anti-TNF therapy achieved weak consensus for agreement. Dispersed opinions were recorded for the final 3 statements.¹

Experts recommend the early use of anti-TNF therapy in many situations for patients with CD and UC, especially among those who have steroid refractoriness, complex perianal disease, severe rectal disease, severe colonic ulcerations, axial spondyloarthritis or peripheral spondyloarthritis and extraintestinal manifestations refractory to conventional therapies, and extensive small bowel involvement.¹

For patients with IBD after a drug holiday, experts recommend therapy be re-introduced if relapse of disease activity is demonstrated clinically or with laboratory results or imaging. The consensus also recognized the cost-effectiveness profile of anti-TNF biosimilars makes them the first-line drug in a substantial proportion of patients and may increase access to biological therapy.¹

Experts expressed dispersed opinions about stopping anti-TNF treatment and did not reach a consensus about the duration of maintenance or cessation of therapy, although they recognized the possibility of doing so pending a case-by-case evaluation. Switch-in-class was also debated and did not reach a consensus of agreement.¹

“Overall, the early use of anti-TNF therapy is recommended in many situations. Nowadays, the cost-efficacy profile of anti-TNF biosimilars makes them the first-line drug and provides the opportunity to increase access to such biological therapy,” concluded investigators.¹

References:

1. Ardizzone S, Armuzzi A, Caprioli F, et al. Timing of proper introduction, optimization and maintenance of anti-TNF therapy in IBD: Results from a Delphi consensus [published online ahead of print, 2023 Sep 21]. Dig Liver Dis. 2023;S1590-8658(23)00938-6. doi:10.1016/j.dld.2023.09.003
2. Johns Hopkins Medicine. Inflammatory Bowel Disease (IBD). Conditions and Diseases. Accessed October 23, 2023. https://www.hopkinsmedicine.org/health/conditions-and-diseases/inflammatory-bowel-disease
3. US Food and Drug Administration. Information on Tumor Necrosis Factor (TNF) Blockers (marketed as Remicade, Enbrel, Humira, Cimzia, and Simponi). February 25, 2021. Accessed October 23, 2023. https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/information-tumor-necrosis-factor-tnf-blockers-marketed-remicade-enbrel-humira-cimzia-and-simponi