Ustekinumab is effective and safe for ulcerative colitis through 2 years of maintenance therapy

Abstract

SummaryBackgroundThe ongoing UNIFI long‐term extension evaluates subcutaneous ustekinumab for moderate‐to‐severe ulcerative colitis (UC) from weeks 44 through 220.AimsTo assess efficacy (through week 92) and safety (through week 96) during the long‐term extensionMethodsOverall, 399 responders to intravenous ustekinumab induction and who were randomised to maintenance therapy were treated in the long‐term extension (115 received subcutaneous placebo, 141 received ustekinumab 90 mg every 12 weeks [q12w], and 143 received ustekinumab 90 mg q8w). Placebo treatment was discontinued at unblinding after week 44. Partial Mayo scores were collected every 12 weeks and at each dosing visit after unblinding. Safety was evaluated throughout.ResultsAmong all patients randomised in maintenance, symptomatic remission rates (stool frequency = 0/1; rectal bleeding = 0) at week 92 were, 64.5% and 67.6% in the ustekinumab q12w and q8w groups, respectively. Among randomised patients treated in the long‐term extension, 78.7% and 83.2% of patients receiving q12w and q8w, respectively, attained symptomatic remission at week 92; >95% of patients in symptomatic remission at week 92 were corticosteroid‐free. Both ustekinumab groups maintained efficacy through week 92. From weeks 44 to 96, adverse events (AEs) per hundred patient‐years (PY) of follow‐up for combined ustekinumab vs placebo were: 255.68 vs 267.93; serious AEs, 9.34 vs 12.69; malignancies (including non‐melanoma skin cancers), 0.93 vs 1.49; and serious infections, 2.33 vs 2.99. One patient with multiple comorbidities who received one ustekinumab dose after dose adjusting from placebo experienced a fatal cardiac arrest.ConclusionsThe efficacy of ustekinumab in patients with UC was sustained through 92 weeks. No new safety signals were observed (ClinicalTrials.gov number, NCT02407236).

Obesity Is Not Associated With an Increased Risk of Serious Infections in Biologic-Treated Patients With Inflammatory Bowel Diseases

“…However, whether obesity modifies the risk of infections in patients with IBD, particularly those being treated with immunosuppressive agents, has not been well studied. Registry studies of biologic agents, including infliximab (TREAT, ENCORE) and adalimumab (PYRAMID), and open-label extension safety studies of vedolizumab and ustekinumab have not examined whether obesity is a risk factor for serious infections (10)(11)(12)(13)(14)(15)(16). In an open-label extension study of tofacitinib in ulcerative colitis, higher body weight was associated with an increased risk of serious infections (17).…”

Japanese pediatric patient with moderately active ulcerative colitis successfully treated with ustekinumab

“…Ustekinumab is effective and safe for inducing and maintaining remission in adult patients with moderate to severe UC [3,5,6] . Although the off-label use of ustekinumab in the pediatric population is increasing, data on its use in children remain scarce, especially for UC [14] .…”

“…Ustekinumab is a first-in-class therapeutic human immunoglobulin-G1 kappa monoclonal antibody that binds to interleukin-12 and interleukin-23, which are cytokines that modulate the function of lymphocytes such as T-helper (Th)-1 and Th17 cell subsets [1] . Ustekinumab is effective in treating adult Crohn disease (CD) and ulcerative colitis (UC) [2–6] . However, data on its efficacy and safety in pediatric CD and UC are limited, [7] although its effectiveness has recently been reported to be similar to that in adult CD and UC [8–10] .…”

Positioning biologics and small molecules in the management of moderate to severe ulcerative colitis

“…UST is safe and well tolerated with serious AE's not commonly reported. No new safety signals have emerged in longer term safety data [19]. In fact, from weeks 44 to 96, AEs, serious AEs, malignancies, and serious infections per hundred patient-years of follow-up were numerically lower in the UST treated groups compared to placebo.…”