Anti-IL-12/23p40 antibodies for induction of remission in Crohn's disease

Abstract

Although we are uncertain about the efficacy of ustekinumab for induction of remission, moderate quality evidence suggests that ustekinumab may be effective for induction of clinical improvement in patients with moderate to severe CD. Due to small numbers of patients in dose subgroups the optimal dosage of ustekinumab is unclear. Briakinumab and ustekinumab appear to be safe. Due to sparse data we were unable to determine the risk of serious adverse events. Further studies are required to determine the efficacy and safety of ustekinumab in patients with moderate to severe CD. The results of three phase III trials that are currently underway will provide important new information.

New and Evolving Immunotherapy in Inflammatory Bowel Disease

“…Remission rates were not significantly different between ustekinumab and placebo at week 6, but maintenance of remission was significantly higher in patients with an initial response to ustekinumab (41.7 vs. 27.4% placebo; p = 0.03) [24]. Compared to placebo, there was no significant increase in adverse events [20,25,26] except for injection site reactions noted in one study [17] and a higher number of severe infections in another study [24]. A Cochrane review [26] of both trials of ustekinumab in active CD [24,25] found the failure rate to achieve remission with ustekinumab not to be statistically different from placebo [relative risk (RR) 0.94, 95% CI 0.88-1.01] even when subgrouped by dose.…”

“…Compared to placebo, there was no significant increase in adverse events [20,25,26] except for injection site reactions noted in one study [17] and a higher number of severe infections in another study [24]. A Cochrane review [26] of both trials of ustekinumab in active CD [24,25] found the failure rate to achieve remission with ustekinumab not to be statistically different from placebo [relative risk (RR) 0.94, 95% CI 0.88-1.01] even when subgrouped by dose. Ustekinumab was, however, associated with a statistically lower rate of failure of response than placebo (RR 0.79, 95% CI 0.71-0.89), with a subgroup analysis showing a significant difference for the 4.5 mg/kg dose group [26].…”

“…A Cochrane review [26] of both trials of ustekinumab in active CD [24,25] found the failure rate to achieve remission with ustekinumab not to be statistically different from placebo [relative risk (RR) 0.94, 95% CI 0.88-1.01] even when subgrouped by dose. Ustekinumab was, however, associated with a statistically lower rate of failure of response than placebo (RR 0.79, 95% CI 0.71-0.89), with a subgroup analysis showing a significant difference for the 4.5 mg/kg dose group [26]. Of note, mucosal healing assessed in 50 patients in the CERTIFI trial was observed in 8 of 41 patients (19.5%) receiving ustekinumab compared to 1 of 9 patients (11.1%) treated with placebo (not significant; p = 1.00).…”

Therapeutic Antibody‐Based Drugs in the Treatment of Human Inflammatory Disorders

“…These include the anti-TNF mAbs (infliximab, adalimumab, golimumab and certolizumab pegol) and two anti-integrin-blocking mAbs (natalizumab and vedolizumab). In contrast to the benefit evident in neutralising TNF, a contributing role for IL-17 in IBD is still uncertain, and IL-12/IL-23 are likely not the driver cytokines as there is only marginal efficacy from ustekinumab (anti-12/IL-23) in CD patients, and no benefit was evident in initial trials with briakinumab (anti-IL-12/IL-23 p40-neutralising mAbs) [54]. Indeed, brodalumab (anti-IL-17RA-neutralising mAb) caused worsening symptoms in CD [55].…”

Psoriatic Disease 10 Years Later

“…IL-23 sustains Th17 cell responses and gut inflammation 15 . The introduction of the anti-IL-12/23p40 antibody ustekinumab for the treatment of Crohn disease (CD), approved also for PsA and psoriasis, has contributed to the elucidation of a shared pathway between these pathologies based on the IL-23-driven process 16 .…”