Insights From Studies on Ustekinumab: Efficacy, Long-Term Outcomes, and Treatment Persistence in Patients With Ulcerative Colitis

The UNIFI study showed that patients who achieved both histologic and endoscopic improvement of the mucosa (histologic-endoscopic mucosal improvement [HEMI]) following ustekinumab induction therapy proceeded to have higher rates of 1-year clinical remission and 3-year symptomatic remission than patients with histologic or endoscopic improvement alone.^1,2 The UNIFI long-term extension study, presented by Peyrin-Biroulet and colleagues, further assessed ustekinumab as maintenance therapy over 4 years, and focused on patients who achieved symptomatic remission with or with-out HEMI.³

The proportion of patients in symptomatic remission through 200 weeks (approximately 4 years) of ustekinumab treatment was highest among those patients who achieved disease clearance following induction. A total of 73.4% of patients who showed disease clearance after induction achieved symptomatic remission at 200 weeks, compared with 53.5% of patients who achieved symptomatic remission without HEMI and 45.1% of patients who achieved neither symptomatic remission nor HEMI (Figure 3). Similar outcomes were shown for patients who achieved corticosteroidfree symptomatic remission at week 200 (70.9% of patients who achieved disease clearance compared with 52.1% of patients who achieved symptomatic remission without HEMI and 42.7% of patients who achieved neither symptomatic remission nor HEMI).

Figure 3.

The proportion of patients with ulcerative colitis in symptomatic remission through week 200^a-e of UST treatment from the UNIFI study.

^aIncluded patients randomized to receive SC UST at week 0 of maintenance.

^bPatients with insufficient data to evaluate histologic improvement status at the end of induction were excluded.

^cPatients who had both stool frequency and rectal bleeding subscores missing at a visit were considered not to be in symptomatic remission for that visit.

^dPatients who had a prohibited change in UC medication, an ostomy or colectomy, or used a rescue medication after a clinical flare or discontinued study agent owing to lack of therapeutic effect or owing to an AE of worsening of UC before week 44 were considered not to be in symptomatic remission at week 44.

^ePatients who had an ostomy or colectomy or discontinued study agent due to lack of therapeutic effect or owing to an AE of worsening of UC after week 44 and before the designated visit were considered not to be in symptomatic remission.

AE, adverse event; HEMI, histo-endoscopic mucosal improvement; SC, subcutaneous; UC, ulcerative colitis; UST, ustekinumab. Adapted from Peyrin-Biroulet et al. Abstract P2203. Presented at: ACG 2023; October 20-25, 2023; Vancouver, Canada.³

The time to treatment failure was prolonged in patients who achieved disease clearance following ustekinumab induction, which was significantly longer than in patients in symptomatic remission without HEMI (P=.043), who in turn had significantly longer time to treatment failure than patients in neither symptomatic remission nor HEMI (P=.004). Similarly, the rates of Inflammatory Bowel Disease Questionnaire (IBDQ) remission (defined as a total IBDQ score ≥170) at week 200 were highest in those patients with disease clearance after induction therapy (58.2%), compared with patients in symptomatic remission without HEMI (46.5%) and neither symptomatic remission nor HEMI (42.7%).

A separate study presented by Zhdanava and colleagues evaluated treatment persistence during the maintenance phase of therapy among patients with UC who were naive to biologic therapy when they initiated treatment with either ustekinumab or adalimumab (the index biologic therapy).⁴ Persistence is considered an important outcome reflective of both the efficacy and safety of a biologic therapy.^5,6 This study had a retrospective cohort design and used US administrative claims data. Several measures of persistence were assessed as study outcomes.

Persistence on the index biologic was defined as the absence of index biologic therapy exposure gap between the end of supply and the date of next claim or the end of follow-up. The exposure gap was greater than 120 days for ustekinumab (based on twice the duration of the ustekinumab maintenance cycle) and greater than 60 days for adalimumab (based on a maintenance cycle of 2 weeks, with dispensing typically of 2 doses covering 4 weeks). The probability of persistence on the index biologic was significantly higher with ustekinumab compared with adalimumab (83.8% vs 57.6%; hazard ratio [HR], 3.09; 95% CI, 2.29-4.16; log-rank P<.001). Persistence while corticosteroid free was a composite outcome defined as the absence of index biologic therapy exposure gap and of corticosteroid used for at least 14 consecutive days of supply after day 90 postindex. The probability of persistence while corticosteroid free was also higher for ustekinumab than adalimumab (64.9% vs 42.4%; HR, 2.00; 95% CI, 1.63-2.45; log-rank P<.001). Persistence while on monotherapy was a composite outcome defined as the absence of index biologic therapy exposure gap and of immunomodulator (azathioprine, cyclosporine, mercaptopurine, methotrexate, or tacrolimus) and non-index advanced therapy use. Persistence while on monotherapy was significantly higher among ustekinumab-treated patients than adalimumab-treated patients (78.2% vs 50.9%; HR, 2.67; 95% CI, 2.07-3.44; log-rank P<.001).