Spotlight on IBD therapy effects

Three recent studies focused on the effects of commonly used therapies for inflammatory bowel disease (IBD).

The first study found that the biologic infliximab, an antitumor necrosis factor (anti-TNF) drug that impairs vaccine effectiveness and increases susceptibility to serious infection, blunts the body's immune response to COVID-19 infection. Researchers assessed antibody responses to SARS-CoV-2 infections in patients with IBD treated with infliximab compared with a reference cohort treated with vedolizumab, which is not associated with vaccine responses or increased susceptibility to infections. They recruited 6,935 patients from 92 U.K. hospitals between Sept. 22 and Dec. 23, 2020. Results of the study, which was partially industry-funded, were published online on March 22 by Gut.

Rates of symptomatic and proven SARS-CoV-2 infection were similar between groups. Seroprevalence was lower in infliximab-treated patients than in those treated with vedolizumab (3.4% [161 of 4,685] vs. 6.0% [134 of 2,250]; P<0.0001). Compared to vedolizumab, infliximab (odds ratio [OR], 0.66 [95% CI, 0.51 to 0.87]; P=0.0027) and immunomodulator use (OR, 0.70 [95% CI, 0.53 to 0.92]; P=0.012) were independently associated with lower seropositivity in multivariable logistic regression analyses. In patients with confirmed SARS-CoV-2 infection, seroconversion was observed in fewer infliximab-treated than vedolizumab-treated patients (48% [39 of 81] vs. 83% (30 of 36]; P=0.00044). Among other limitations, it is not known whether attenuated immune responses in infliximab-treated patients translates into increased risk of SARS-CoV-2 infection, the study authors noted. “From a public health perspective, impaired serological responses might lead to chronic nasopharyngeal colonisation that may act as a reservoir to drive persistent transmission and the evolution of new SARS-CoV-2 variants,” they wrote.

Another study found that while both infliximab and adalimumab are effective in the long-term treatment of outpatients with IBD in real-life clinical practice, adalimumab appears to be the safer drug. Researchers retrospectively reviewed 712 adult outpatients with an established diagnosis of IBD who were unresponsive to standard treatments and treated with infliximab or adalimumab in 18 Italian IBD centers until Dec. 31, 2018, irrespective of the length of treatment. Patients who completed at least the induction treatment were included. The primary end points were 1) achieving combined remission, defined as Mayo score of 2 or less in patients with ulcerative colitis, and clinical remission, defined as Harvey-Bradshaw Index of 5 or less in patients with Crohn's disease and 2) safety of infliximab and adalimumab, defined as absence of adverse events during treatment. Results were published online on March 19 by the European Journal of Gastroenterology & Hepatology.

The study included 410 patients with Crohn's disease (268 treated with adalimumab, 142 with infliximab; median follow-up, 60 months) and 302 with ulcerative colitis (118 treated with adalimumab, 184 with infliximab; median follow-up, 48 months). In Crohn's disease, clinical remission was maintained in 75.0% of the adalimumab group versus 72.5% of the infliximab group (P=0.699), and mucosal healing and steroid-free remission were maintained in 49.5% of the adalimumab group versus 63.9% of the infliximab group (P=0.077) and in 77.7% of the adalimumab group versus 77.3% in the infliximab group (P=0.957), respectively. In ulcerative colitis, clinical remission was maintained in 50.0% of the adalimumab group versus 65.8% of the infliximab group (P<0.000), and mucosal healing and steroid-free remission were maintained in 80.6% of the adalimumab group versus 77.0% of the infliximab group (P=0.494) and in 90.2% of the adalimumab group versus 87.5% of the infliximab group (P=0.662), respectively. Infliximab was more likely to cause adverse events than adalimumab (16.6% vs. 6.2%, P<0.000). The two main limitations of the study were its retrospective design and the overall inclusion of patients with moderate rather than severe IBD, the authors noted.

The third study found that anti-TNF therapy may be associated with reduced mortality compared with long-term corticosteroid use in certain patients with IBD. Researchers looked at a Veterans Health Administration cohort of patients with IBD treated with prolonged corticosteroids (≥3,000-mg prednisone equivalent and/or ≥600 mg of budesonide within a 12-month period) and/or new anti-TNF therapy from Jan. 1, 2006, to Oct. 1, 2015. The primary end point was all-cause mortality, defined by the Veterans Health Administration vital status file. Results were published on March 1 by JAMA Network Open.

A total of 2,997 patients (mean age, 50.0 years; 90.9% men) were included in the final analysis, 1,734 (57.9%) with Crohn's disease and 1,263 (42.1%) with ulcerative colitis. All-cause mortality was 8.5% (n=256) over a mean of 3.9 years of follow-up. At cohort entry, 1,836 patients were new anti-TNF therapy users and 1,161 were prolonged corticosteroid users. Anti-TNF therapy use was associated with a lower likelihood of mortality for patients with Crohn's disease (OR, 0.54; 95% CI, 0.31 to 0.93) but not for those with ulcerative colitis (OR, 0.33; 95% CI, 0.10 to 1.10). However, in a sensitivity analysis that adjusted prolonged corticosteroid users to include patients receiving corticosteroids within 90 to 270 days after initiation of anti-TNF therapy, the OR for patients with ulcerative colitis was statistically significant at 0.33 (95% CI, 0.13 to 0.84) and the OR for those with Crohn's disease was 0.55 (95% CI, 0.33 to 0.92). Limitations of the study include its use of administrative data and the potential for residual confounding, the authors said. “[The results support] prior high-quality studies of Medicaid and Medicare beneficiaries. Given the observation that older patients with more comorbidities do not seem to receive anti-TNF agents to the same degree as their younger, healthier counterparts, there is an urgent need to recognize the benefit associated with anti-TNF therapy vs corticosteroid use in such populations,” they concluded.