SUMMARY

• The company cannot recommend any practices, procedures, or usage that deviate from the approved labeling.
• A phase 2 study and case report describing the use of STELARA in patients with RA are described below.^1,2

CLINICAL DATA

Phase 2 Study

Smolen et al (2017)¹ conducted a phase 2, randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of subcutaneous (SC) STELARA and guselkumab in patients with active RA (>=6/66 swollen joints and >=6/68 tender joints plus a serum C reactive protein (CRP) level >=0.8 mg/dL) despite treatment with methotrexate (MTX). Further, all patients received MTX (10-25 mg/week) for ≥6 months before screening, including treatment at a stable dose for ≥12 weeks.

Study Design/Methods

• A total of 274 adult RA patients were randomized (1:1:1:1:1) to receive placebo (PBO) plus MTX (n=55), or STELARA 90 mg plus MTX (n=55), or guselkumab 50 mg plus MTX (n=55), or guselkumab 200 mg plus MTX (n=54) at weeks 0, 4, and every 8 weeks, or STELARA 90 mg plus MTX (n=55) at weeks 0, 4, and every 12 weeks through week 28.
• At week 16, patients in the PBO group who had <10% improvement from baseline in both tender and swollen joint counts entered double-blind early escape and received STELARA 90 mg at weeks 16, 20 and 28; no treatment adjustments were made for patients randomized to the STELARA or guselkumab groups.
• Patients were permitted to continue stable doses of oral corticosteroids or nonsteroidal antiinflammatory drugs (NSAIDs), or other analgesics for RA.
• Patients were ineligible if they received any approved or investigational biologic agents.
• The primary endpoint included the proportion of patients achieving a 20% improvement according to the American College of Rheumatology criteria (ACR20) at week 28.
• Other efficacy endpoints included 28-joint count Disease Activity Score using CRP (DAS28-CRP), Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI). Health-related quality of life and physical function were assessed using the 36-item Short-Form Health Survey (SF-36) and the Health Assessment Questionnaire-Disability Index (HAQ-DI).

Results

Efficacy

• At week 28, statistically significant differences in ACR20 response between the PBO group (40%) as compared with the combined STELARA group (53.6%; P=0.101) and the combined guselkumab group (41.3%; P=0.877) were not observed. At week 28, ACR20 response was reported in 40.0% of patients in the placebo + MTX group, 52.7% in the STELARA 90 mg + MTX every 8 weeks group, 54.5% in the STELARA 90 mg + MTX every 12 weeks group, 38.2% in the guselkumab 50 mg + MTX group, and 44.4% in the guselkumab 200 mg + MTX group, respectively.
• Since statistical significance was not achieved for the primary endpoint, a nominal significance level was applied to secondary endpoints and other analyses.
• Results for primary and secondary endpoints through week 28 are provided in Table: Secondary Efficacy Assessments at Week 28.

Safety

• The proportion of patients with at least at least 1 adverse event (AE) through week 16, before early escape and through week 48 were comparable among the treatment groups.
• The incidence of patients with ≥ 1 serious adverse event (SAE) was low and similar across treatment groups through week 48 (PBO+MTX; 5.5% [n=3], STELARA 90 mg every 8 weeks; 7.4% [n=4], STELARA 90 mg every 12 weeks; 5.5% [n=3], guselkumab 50 mg every 8 weeks + MTX; 0% [n=0], guselkumab 200 mg every 8 weeks + MTX; 5.6% [n=3]).
• Through week 48, the most common type of AE was infections.
• Two malignancies were reported including squamous cell carcinoma of the lung in the STELARA 90 mg every 12-week-group and breast cancer in the guselkumab 200 mg group.
• One death occurred in the STELARA 90 mg every 8-week-group for which the exact cause of death could not be confirmed. There were no reports of tuberculosis or opportunistic infections.

Case Report

Chimenti et al (2015)² reported a case of PsO treated with STELARA in a patient with a 6 year history of coexisting RA.

• A 60-year old woman with RA, arterial hypertension and previous tuberculosis developed diffuse cutaneous PsO during treatment with adalimumab 40 mg SC every 2 weeks plus MTX 15mg weekly.
• At the time of RA diagnosis, laboratory tests were: erythrocyte sedimentation rate (ESR) was 48mm/h, C-reactive protein (CRP) was 13mg/L (NV <3mg/L), rheumatoid factor (RF) was 313 IU/mL (NV<15 IU/mL) and anti-citrullinated protein antibodies (ACPA) were 165 IU/mL (NV<20 IU/mL).
• Prior treatments, which were ineffective or not well tolerated, included MTX, sulfasalazine, leflunomide, hydroxychloroquine, glucocorticosteroids and etanercept.
• After 12 months of adalimumab treatment, diffuse psoriatic plaques with palmoplantar involvement with a Psoriasis Area and Severity Index Score (PASI) of 28 was observed.
• The patient started treatment with STELARA 45 mg SC injections and after 12 weeks, reported cutaneous improvement with a PASI score of 10 as well as stable articular disease with no swelling and/or joint tenderness.
• After 24 weeks of treatment with STELARA, psoriasis of the hand and feet with a PASI score of 6.1 was reported.
• After 28 weeks, complete resolution of skin involvement (PASI 0) and stability of the joints (DAS28-ESR 1.9) were observed and the patient was reported as stable during a followup after 3 years of treatment with the following laboratory test results and: ESR 16, CRP 0 mg/L, RF 32,7 IU/mL, ACPA 123 IU/mL.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, DERWENT^® (and/or other resources, including internal/external databases) was conducted on 1 February 2024.