Spotlight on IBD therapy comparisons

Multiple recent studies compared effects of medications for inflammatory bowel disease (IBD).

The first study, published by the American Journal of Gastroenterology (AJG) on July 12, used a cohort of Swedish patients with IBD to compare infection rates with vedolizumab versus anti-tumor necrosis factor (TNF) therapy. Among 1,376 cases of Crohn's disease, the rate of serious infections was significantly higher with vedolizumab (5.18 [95% CI, 3.98 to 6.63] vs. 3.54 [95% CI, 2.50-4.85] per 100 person-years; hazard ratio [HR], 1.72 [95% CI, 1.12 to 2.65]). However, among 1,294 studied cases of ulcerative colitis (UC), the rate of serious infections was similar between vedolizumab and anti-TNF therapy (3.74 vs. 3.42 per 100 person-years; HRs, 0.80 [95% CI, 0.47 to 1.36] during the initial 1.1 years and 2.03 [95% CI, 0.65 to 6.32] afterward). "As a clinician, it is important to be aware of the increased risk of serious infections in patients with IBD, linked to both immunosuppressive therapies and disease activity, which this study highlights," said the authors, who noted that the results indicate that "the panorama of serious infections seemed to differ between the drugs."

The second study, published by the New England Journal of Medicine on July 17, was a manufacturer-sponsored noninferiority trial of risankizumab for patients with moderate-to-severe Crohn's disease who had inadequate response to anti-TNF therapy. The open-label trial randomized 255 patients to risankizumab and 265 to ustekinumab. At 48 weeks, 90.2% of the risankizumab group and 72.8% of the ustekinumab group had completed all assigned treatments. At week 24, full clinical remission had been achieved in 58.6% of risankizumab patients and 39.5% of ustekinumab patients (adjusted difference, 18.4 percentage points; 95% CI, 6.6 to 30.3 percentage points). At week 48, endoscopic remission was more common with risankizumab (31.8% vs. 16.2%; adjusted difference, 15.6 percentage points [95% CI, 8.4 to 22.9 percentage points]). "The superior efficacy of risankizumab over ustekinumab that we observed aligns with findings in previous head-to-head clinical trials involving patients with moderate-to-severe plaque psoriasis," the study authors noted, adding that it's not known why "targeted inhibition of interleukin-23 shows greater efficacy than inhibition of both interleukin-12 and interleukin-23."

An accompanying editorial advised against drawing such a broad conclusion from this trial. "Differences in responses to therapies among patients with Crohn's disease may be influenced by the clinical phenotype, the biologic pathways driving disease, the stage of disease, and previous therapeutic interventions. Additional head-to-head trials of interleukin-23 p19 and interleukin-12 p40 that evaluate distinct patient subpopulations will be important," it said.

Finally, a study published by AJG on July 5 looked retrospectively at patients with UC to compare the effectiveness of upadacitinib and tofacitinib. A total of 526 patients on upadacitinib and 1,149 taking tofacitinib were included and propensity score matched. On the study's primary outcome of hospitalization requiring IV steroids and/or colectomy, there was no significant difference between drugs at six months. However, at 12 months, there was a lower risk of the composite outcome with upadacitinib (adjusted odds ratio [aOR], 0.63; 95% CI, 0.44 to 0.89), driven by a lower risk of colectomy (aOR, 0.46; 95% CI, 0.27 to 0.79). A sensitivity analysis found reduced risk of steroid use, colectomy, and the composite outcome (aOR, 0.64; 95% CI, 0.44 to 0.94) at 12 months. "The differences observed in outcomes between upadacitinib and tofacitinib cohorts highlight the importance of understanding the unique mechanisms of action of these Janus kinase (JAK) inhibitors. While tofacitinib inhibits multiple JAKs, including JAK2, JAK3, and TYK2, upadacitinib selectively targets JAK1," the study authors said, noting that the more specific target may increase effectiveness by allowing higher dosing of the drug.