Management of Primary Nonresponders and Partial Responders to Tumor Necrosis Factor-α Inhibitor Induction Therapy among Patients with Crohn’s Disease

Abstract

Induction therapy with tumor necrosis factor-α (TNF-α) inhibitors is highly effective for the treatment of Crohn’s disease. However, there are primary nonresponders (PNR) of TNF-α inhibitors without clinical response during the induction period. In addition, there are partial responders (PR), who show some efficacy, but clinical remission is not achieved by induction therapy. To date, the definition and clinical management of PNR and PR have not been established. This report summarizes the opinions of 36 Japanese experts attending the Japan Round Table Discussion on IBD Meeting regarding how to determine PNR and PR of TNF-α inhibitors and how to manage these patients in clinical practice. PNR, who do not show any initial improvement of clinical symptoms and serum C-reactive protein (CRP) levels, require re-assessment of intestinal complications. PR can be determined either by clinical symptoms, serum CRP levels, or imaging results. PR need intensification of the treatment with TNF-α inhibitors either with or without optimization of immunomodulators. Optimization of initial TNF-α inhibitor therapy may improve long-term outcomes, but more evidence is required to improve the use of TNF-α inhibitors for the prevention and management of PNR and PR.

Genetic association of primary nonresponse to anti-TNFα therapy in patients with inflammatory bowel disease

“…We observed a 15%PNR in CD patients versus 32% PNR in UC patients in our discovery cohort. Previous studies on anti-TNFα nonresponse report 10–15% PNR in CD patients and 30–32% PNR in UC patients [2–5]. Therefore, even with a small sample size, the observed frequency of PNR in our GWAS cohort by disease subtypes are in line with previously reported frequency in CD and UC patients.…”

“…Despite substantial efficacy of antitumor necrosis factor-alpha (anti-TNFα) biologics in the treatment of inflammatory bowel disease (IBD), 8-42% of patients do not respond [primary nonresponders] to therapy [1][2][3][4][5]. Primary nonresponse (PNR) to anti-TNFα has serious implications on disease course, including reduced likelihood of response to a second anti-TNF agent, and a greater need for surgery [6].…”

PERFUSE: Non-Interventional Cohort Study of Patients Receiving Infliximab Biosimilar SB2: Results in Pediatric Patients

“…Primary failure was deined as "treatment failure occurring within 14 weeks of IFX initiation" and classiication was left up to the treating physician. Though this leads us to report lower levels of primary failure than other studies using broader deinitions, overall persistence in naïve patients over the course of the irst 3 months is within the range observed in other pediatric IFX studies (between 60% and 90% persistence at 8-10 weeks, depending on the study) (40)(41)(42). The proportion of secondary nonresponders relative to the overall population size (UC: 55.6% and CD: 13.7%; UC: 13.3% and CD: 7.8%, for naïve and switched patients, respectively) was in line with other IFX studies (between 13% and 20% loss of response per patient year), except for naïve UC patients for whom it was higher (42,43).…”

Could Mucosal TNF Transcript as a Biomarker Candidate Help Optimize Anti-TNF Biological Therapy in Patients With Ulcerative Colitis?

“…Currently, neutralizing TNF monoclonal antibodies have been widely accepted as one of the standard strategies for the treatment of severe steroid or immunomodulator-refractory or -dependent IBD patients ( 12 ), which results in remarkably improved rates of disease remission and mucosal healing ( 12 ). Even so, not all IBD patients respond well to anti-TNF therapy ( 13 ); the primary response rate to the initial anti-TNF treatment is only ~60% and 20~30% of these responders will stop responding at some point during maintenance therapy ( 13 – 17 ). Furthermore, more than 30% of IBD patients in remission during the first year and over 60% of IBD patients in remission within 5 years will relapse after withdrawal of anti-TNF bioagents ( 13 , 18 , 19 ).…”