Non-Anti-TNF-a Antibody Therapies Effective as Second-Line Treatment for Ulcerative Colitis

UC colonoscopy
ulcerative colitis, biopsy, microscopic image, colonoscopy, IBD
Investigators examined whether a patient’s initial response to anti-tumor necrosis factor (TNF)-a antibody could inform subsequent treatment in ulcerative colitis.

Non-anti-tumor necrosis factor (TNF)-a antibody (ATA) therapy may be a suitable second-line treatment option for patients with ulcerative colitis (UC) who were nonresponsive to first-line ATA treatment, according to study results published in the Journal of Gastroenterology and Hepatology.

For the retrospective analysis, researchers reviewed 163 patients with UC who were treated with ATA as the first biologic between 2009 and 2020 at Chiba University Hospital in Japan for clinical outcomes. Treatment efficacy was evaluated using the partial Mayo score (pMayo). Patients with pMayo scores less than or equal to 1 throughout the study period were excluded from the analysis.

Study participants had a median age of 38 (range, 18-74) years; 99 patients were men; and the disease duration was 4.0 (range, 0-42.0) years.

As first-line therapy, 113 received infliximab, 41 adalimumab, and 9 golimumab. After first ATA, 17.8% achieved remission, 42.3% had response, 34.4% had primary nonresponse, and 5.5% had intolerance.

Overall, patients had a median pMayo score of 5 (range, 0-9); 80 were receiving corticosteroids, 59 immunomodulators, 32 calcineurin inhibitors; white blood cell count was 7.9 (range, 2.7-21.9) ´ 1000/mL; C-reactive protein was 0.50 (range, 0-11.4) mg/dL; and albumin was 3.8 (range, 2.0-4.8) g/dL.

During the course of treatment, 63 switched to a second ATA and 36 switched to non-ATAs.

As second-line therapies, 28 received golimumab, 20 adalimumab, 20 tofacitinib, 15 infliximab, 9 vedolizumab, and 7 ustekinumab. Among the ATA second-line therapies, 20.1% achieved remission, 31.7% had response, 46.0% had primary nonresponse, and 2.2% had intolerance. For non-ATA second-line therapies, 38.9% achieved remission, 19.4% had response, 33.3% had primary nonresponse, and 8.4% had intolerance.

Among the cohort of patients with primary nonresponse, 78.3% and 42.1% also had nonresponse to their second-line therapy among the ATA and non-ATA cohorts, respectively (P <.01).

Among the second-line therapy groups, no significant clinical characteristics were observed between the ATA and non-ATA recipients.

In the multivariate analysis, primary nonresponse to first ATA was a significant predictor for nonresponse to second-line ATA (OR, 5.69; 95% CI, 1.50-21.7; P =.01). For nonresponse to second-line non-ATA, the only predictor was age younger than 28 years (OR, 29.8; 95% CI, 1.87-473; P =.02).

This study was limited by its single-center design and small sample size.

“According to our results, non-ATA showed a better response and remission rate than

ATA as subsequent therapy to patients who had received ATA, regardless of the efficacy of the initial ATA,” the study authors noted. “Therefore, routine selection of non-ATA rather than ATA may be reasonable as subsequent therapy to initial ATA failure.”


Kanayama K, Kato J, Shiratori W, et al. Anti-TNFα antibody versus non-anti-TNFα molecular agents for ulcerative colitis patients who failed initial anti-TNFα therapy. J Gastroenterol Hepatol. Published online March 9, 2022. doi:10.1111/jgh.15826