SUMMARY

• The company cannot recommend any practices, procedures, or usage that deviate from the approved labeling.
• A post hoc analysis including the UNITI-1, UNITI-2, and IM-UNITI studies reported the incidence of resolution of uveitis or iritis in patients treated with STELARA.¹
• A prospective study and case reports describe the use of STELARA in patients with uveitis.^2,3

CLINICAL DATA

UNITI Trial Program

The efficacy and safety of STELARA was evaluated in 3 randomized, double-blind, placebocontrolled phase 3 clinical studies in adult patients (≥18 years of age) with moderately to severely active Crohn’s disease (CD) (Crohn’s Disease Activity Index [CDAI] score of 220 to 450). There were two 8-week intravenous (IV) induction studies (UNITI-1 and UNITI-2), followed by a 44-week subcutaneous (SC) randomized withdrawal maintenance study (IM-UNITI), representing 52 weeks of therapy.⁴ All patients (randomized and non-randomized) who completed the efficacy and safety assessment at week 44 of the IM-UNITI maintenance study were eligible to participate in the IM-UNITI extension (up to 4 years) and continued to receive the same treatment as they were receiving at week 44 of the IM-UNITI maintenance study (no dose adjustment occurred in the long-term extension [LTE]).^4,5

In the UNITI program, baseline and disease characteristics were similar among the treatment groups. Patients were allowed to have stable doses of immunosuppressants, mesalamine, antibiotics, or oral glucocorticoids (≤40 mg prednisone daily or ≤9 mg budesonide daily) or a combination of these. In patients who had a response to induction treatment and who were receiving glucocorticoids, tapering was initiated at week 0 of the IM-UNITI trial.⁴

UNITI-1 and UNITI-2 IV Induction Studies

UNITI-1 was a phase 3, randomized, double-blind, placebo-controlled, multicenter study that was conducted to evaluate the efficacy and safety of 2 STELARA IV induction regimens in adult patients with moderately to severely active CD (CDAI 220-450) who failed or were intolerant to 1 or more tumor necrosis factor (TNF) blockers.^4,6,7

UNITI-2 was a phase 3, randomized, double-blind, placebo-controlled, multicenter study that was conducted to evaluate the efficacy and safety of 2 STELARA IV induction regimens in adult patients with moderately to severely active CD who had failed or were intolerant to oral steroid and/or immunosuppressive therapy (ie, azathioprine, mercaptopurine, or methotrexate), but were not refractory to TNF blocker therapy. Patients were allowed to have previously received ≥1 TNF blocker but couldn’t have been intolerant to the TNF blocker(s) and had not met the criteria for primary or secondary nonresponse to the treatment.^4,8,9

IM-UNITI SC Maintenance Study

IM-UNITI was a phase 3, randomized, double-blind, placebo-controlled, multicenter study that was conducted to evaluate the efficacy and safety of 2 maintenance SC regimens of STELARA in patients with moderately to severely active CD who responded to IV treatment with STELARA in the UNITI-1 and UNITI-2 studies.^4,10,11

Post Hoc Analysis - UNITI-1, UNITI-2, and IM-UNITI

Narula et al (2021)¹ reported results from a post hoc analysis of the UNITI-1, UNITI-2, and IM-UNITI studies.

Study Design/Methods

• In UNITI-1 and UNITI-2, at week 0, patients were randomized in a 1:1:1 ratio to receive a single dose of IV placebo, or IV STELARA 130 mg, or weight-based IV STELARA dosing approximating 6 mg/kg (260 mg [weight ≤55kg], 390 mg [weight >55kg and ≤85kg], 520 mg [weight >85kg]). The primary endpoint was clinical response at week 6 (defined as a reduction from baseline in CDAI score of ≥100 points or a CDAI score of <150).^1,7,9
• In IM-UNITI, patients who were in clinical response at week 8 to IV STELARA during the UNITI-1 or UNITI-2 induction study were randomly assigned in a 1:1:1 ratio to receive (through week 40) SC placebo, or STELARA 90 mg SC every 8 weeks, or STELARA 90 mg SC every 12 weeks. The primary endpoint was clinical remission at week 44 (CDAI score <150).^1,11
• The outcomes of the post hoc analysis are as follows:
  • The primary outcome was overall resolution of extraintestinal manifestations (EIM) at week 6 in patients treated with STELARA vs placebo.
  • The secondary outcome was overall resolution of EIM at week 52 and individual resolution of EIMs and de novo development of EIMs at weeks 6 and 52 in patients treated with STELARA vs placebo, and the prevalence of active EIM at weeks 6 and 52 vs baseline in patients treated with STELARA.
• Prevalence was defined as the presence of an EIM of interest at the respective visit; resolution was defined as the absence of an EIM which had previously been reported as present; de novo was defined as the development of new or return of EIMs at weeks 6 or 52 of STELARA therapy that were not present at baseline.

Results

• Of the 941 STELARA-treated patients in UNITI-1 and UNITI-2, 504 had 527 EIMs at baseline.
• Among the 941 patients, 23 (2.4%) had uveitis or iritis at baseline.  
  • At week 6, overall resolution of EIM was not statistically significant in patients treated with STELARA vs placebo (186 of 504 [36.9%] vs 90 of 230 [39.1%]; P=0.564).
  • At week 6, among patients with uveitis or iritis at baseline, no significant improvement was observed in patients treated with STELARA vs placebo (15 of 23 [65.2%] vs 9 of 16 [56.3%]; P=0.571).
  • At week 6, among the overall population, uveitis or iritis resolved in 15 of 941 (1.6%) patients and prevailed in 12 of 941 (1.3%) patients (P=0.019 for both); de novo uveitis or iritis was reported in 4 of 941 (0.4%) patients.
• Of the 263 STELARA-treated patients in IM-UNITI, 119 had 147 EIMs at baseline.
• Among the 263 patients, 8 (3.0%) had uveitis or iritis at baseline.
  • At week 52, overall resolution of EIM was not statistically significant in patients treated with STELARA vs placebo (91 of 119 [76.4%] vs 72 of 90 [80.0%]; P=0.542).
  • At week 52, among patients with uveitis or iritis at baseline, no significant improvement was observed in patients treated with STELARA vs placebo (7 of 8 [87.5%] vs 7 of 8 [87.5%]; P=1.000).
  • At week 52, among the overall population, uveitis or iritis resolved in 7 of 263 (2.7%) patients and prevailed in 1 of 263 (0.4%) patients (P=0.070 for both); no patients reported de novo uveitis or iritis.

Prospective Study

Utriainen et al (2018)² reported the results of a prospective, nonrandomized, uncontrolled, phase 1/2 pilot study to investigate the safety, tolerability, and potential efficacy of high-dose SC STELARA for the treatment of active posterior segment uveitis.

Study Design/Methods

• A total of 4 patients were recruited of the 5 patients that were planned for the study.
• Patients received 3 doses of STELARA 90 mg SC at baseline, week 4, and week 8.
• The study duration was 28 weeks with the primary endpoint being the number of patients experiencing treatment response, defined as no active chorioretinal lesions and ≤0.5 anterior chamber (AC) cells or vitreous haze by week 16.
• Peripheral blood mononuclear cells (PBMC) and serum samples were collected at baseline and weeks 4, 8, 16, and 28.
• It was analyzed whether Th1, Th17, and T regulatory (Treg) cell populations were affected by STELARA treatment.

Results

• Three of the 4 patients met the treatment response criteria by 16 weeks.
• A slight increase in the percentage of Tregs, defined as CD25⁺CD127^loFoxp3⁺ cells, was seen in all patients by week 4 compared to baseline. This persisted until week 8, when the percentage of Tregs started to decline.
• The percentage of Th17 cells, defined as CCR6⁺ IL-17⁺, slightly decreased by week 8 compared to baseline in 2 patients.
• IFNγ⁺ CD4⁺ T cells, most likely to be Th1 cells, showed no apparent changes in response to STELARA treatment.
• The majority of patients experienced an improvement in their active posterior segment uveitis, which appeared to correlate with the expansion of Tregs.
• STELARA was well tolerated and no serious adverse events were reported.

Case Reports

Mugheddu et al (2017)³ reported the use of STELARA in a patient with noninfectious uveitis and concomitant severe psoriatic arthritis and plaque psoriasis.

• The patient was a 64-year-old female with a 4-year history of pustular palmo-plantar psoriasis, psoriatic arthritis, Reynaud’s phenomenon, and acute anterior uveitis.
• Treatment with 3 mg/kg/day of cyclosporine A (CsA) provided improvement of ocular manifestations before she experienced a worsening of psoriasis (Psoriasis Area Severity Index [PASI]:12.7) and uveitis, with severe visual impairment.
• Treatment was initiated with adalimumab 80 mg followed by 40 mg every other week.
• Adalimumab was discontinued after developing a severe urticarial rash 2 weeks after her first 40 mg dose and she received prednisone 25 mg/day for 5 days followed by tapering.
• CsA 3 mg/kg/day was restarted due to worsening of psoriasis, joint pain, and uveitis and led to a rapid and complete remission.
• Five months later, after a psoriasis flare (PASI:22) and severe visual deterioration, treatment with STELARA 45 mg SC injection at week 0, week 4, and every 12 weeks was initiated.
• After receiving 3 doses of STELARA, symptoms of psoriasis were resolved with control of her uveitis manifestations.
• The patient still suffered from joint pain and the STELARA dose was increased to
• 90 mg every 12 weeks.
• After 52 weeks of treatment, she had complete remission of uveitis symptoms with preserved visual acuity and her psoriasis and psoriatic arthritis were both controlled.

Chateau et al (2019)¹² describe two case reports of female patients (age 49 and 60) with CD associated non-infectious uveitis treated with STELARA.

• Both patients were diagnosed with ileocolonic CD in 1993 and had undergone ileocecal resection.
• Patients were treated with adalimumab 40 mg weekly.
  • One patient with spondyloarthritis also received methotrexate.
• Each patient presented with disabling non-infectious uveitis flares with severe visual loss in both eyes every year which required repeated courses of topical and systemic corticosteroids.
• One patient had a simultaneous diagnosis of progressive multiple sclerosis.
• Both patients received STELARA with an induction infusion of 390 mg followed by SC injections of 90 mg every 8 weeks.
• Following treatment with STELARA for 6 and 10 months, respectively, no recurrence of noninfectious uveitis symptoms have been observed.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 15 March 2024.