Second-line ustekinumab for Crohn’s disease holds up in real world, as good as vedolizumab

Ustekinumab is well tolerated and proves to be effective in the second-line treatment of patients with Crohn’s disease (CD), according to real-world data from the Cross Pennine II study. Furthermore, while clinical remission appears to occur sooner with ustekinumab than with vedolizumab, the two drugs perform comparably at maintaining remission over 12 months.

Cross Pennine II included a real-world cohort of 282 CD patients (mean age 40 years) who had been treated with ustekinumab for a mean of 18 months across several IBD centres in the UK. A total of 200 patients (70.9 percent) achieved clinical response or remission at 14 weeks, and 162 of them (62.5 percent) maintained remission at 52 weeks. There were 74 adverse events documented, of which 26 were labelled as serious (8.3 per 100 person-years). [Aliment Pharmacol Ther 2022;doi:10.1111/apt.16742]

Failure to ustekinumab treatment at 14 weeks was associated with high baseline Harvey-Bradshaw Index (HBI; odds ratio [OR], 1.12, 95 percent confidence interval [CI], 1.01–1.24; p=0.024) and penetrating and stricturing disease behaviour (Montreal B2: OR, 1.47, 95 percent CI, 0.33–6.47; p=0.608; Montreal B3: OR, 3.49, 95 percent CI, 1.01–12.1; p=0.05). At 52 weeks, predictors of treatment failure included current smoking, baseline HBI or physician global assessment, and use of steroids.

A propensity score-matched analysis was conducted to compare ustekinumab and vedolizumab. This included 275/282 patients (97.5 percent) on ustekinumab and 118/135 patients (87.4 percent) ustekinumab-naïve patients who were treated with vedolizumab after failing any anti-TNFα agent from the Cross Pennine study. [Dig Liver Dis 2018;50:1299-1304]

Patients on ustekinumab were 38-percent (95 percent confidence interval [CI], 25–50; p<0.001) more likely to achieve clinical remission at 14 weeks. At 52 weeks, the difference shrank to a nonsignificant 9 percent (95 percent CI, −15 to 33; p=0.462).

Almost all patients in the Cross Pennine II cohort had already been exposed to a biologic agent, and roughly half had had CD-related abdominal surgery. Of note, 222 patients (78.7 percent) had at least one comorbidity, with the most common being essential hypertension, ischaemic heart disease, psoriasis, and type 2 diabetes.

“Our findings confirm that ustekinumab allows a more rapid achievement of clinical remission compared to vedolizumab, which may take a few more weeks for reaching this goal, as is already known,” according to the investigators. [World J Gastroenterol 2017;23:6385-6402]

“However, at 52 weeks, both drugs are effective in maintaining remission, although some predictors of treatment failure were found for ustekinumab, and these should be taken into account when choosing therapy,” they pointed out.

Vedolizumab is the second class of monoclonal antibodies to be licensed after anti-TNF therapies. Its efficacy and safety have been demonstrated in long-term extension studies and real-world studies. Meanwhile, ustekinumab is latest monoclonal antibody to be approved for the induction and maintenance of CD. [Aliment Pharmacol Ther 2020;52:1353-1365; Dig Liver Dis 2018;50:1299-1304; Dig Liver Dis 2019;51:68-74]

Aside from targeting a crucial inflammatory pathway in CD, ustekinumab is also effective in treating some CD-related extra-intestinal manifestations, especially dermatologic and rheumatologic, such as psoriasis and psoriatic arthritis. However, real-world data exploring the drug’s efficacy and safety in CD are still emerging, as are comparative studies with vedolizumab in anti-TNFα-experienced patients. [J Crohns Colitis 2021;15:1236-1243; Ann Rheum Dis 2016;75:1984-1988]