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OP0031 A Phase 2 Study Evaluating the Efficacy and Safety of Subcutaneously Administered Ustekinumab and Guselkumab in Patients with Active Rheumatoid Arthritis Despite Treatment with Methotrexate
  1. J. Smolen1,
  2. S.K. Agarwal2,
  3. E. Ilivanova3,
  4. X.L. Xu4,
  5. Y. Miao5,
  6. S. Mudivarthy6,
  7. W. Xu6,
  8. W. Radziszewski4,
  9. A. Greenspan7,
  10. A. Beutler6,
  11. D. Baker6
  1. 1Medical University of Vienna, Vienna, Austria
  2. 2Baylor College of Medicine, Houston, United States
  3. 3Leningrad Region Clinical Hospital, St.Petersburg, Russian Federation
  4. 4Janssen R&D, LLC, La Jolla
  5. 5Janssen R&D, LLC
  6. 6Janssen R&D, LLC, Spring House
  7. 7Janssen Scientific Affairs, LLC, Horsham, United States

Abstract

Objectives To evaluate UST (anti-IL-12/23p40 mAb) and GUS (investigational anti-IL-23p19 mAb) in reducing signs and symptoms in active RA despite MTX.

Methods In this Ph2, randomized, double-blind, multicenter, PBO-controlled, parallel-group study, patients (18-80yrs) with active RA (≥6 tender joint count [TJC] and 6 swollen joint count [SJC] and serum CRP≥0.80mg/dL) despite MTX, were randomized to the following through wk28 (with MTX): PBO wks 0,4, q8wks; UST90mg wks 0, 4, q8wks; UST90mg wks 0, 4, q12wks; GUS200mg wks 0, 4, q8wks; or GUS50mg wks 0, 4, q8wks. Patients were on MTX (10mg-25mg/wk) for ≥6 months with stable dose for a minimum of 12wks prior to randomization. Oral prednisone/equivalent (≤10 mg/day) and NSAIDs were permitted; previous and concomitant use of biologics not permitted. At wk16, PBO patients who failed to achieve ≥10% improvement (both TJC and SJC) received UST 90mg at wk16, 20, and 28. All patients were followed for safety through wk48. Primary endpoint was ACR20 response at wk28.

Results 274 patients were enrolled; 22 (8.0%) d/c through wk28. Major reasons for d/c: lack of efficacy (10 [3.6%]);AEs (8 [2.9%]). Patient demographics were generally similar between groups. Baseline clinical disease characteristic were well balanced across groups except median disease duration (slightly longer in PBO [6.3yrs] vs UST [4.15 yrs] and GUS [4.30 yrs] groups). Baseline median CRP for all patients was 1.5mg/dL and median SJC and TJC were 14 and 24, resp. Proportion of patents with ACR20 did not differ significantly between groups; however some differences were observed for secondary endpoints (Table). Through wk48, 45.5% PBO, 50.4% combined UST, and 43.1% combined GUS had ≥1 treatment-emergent adverse events (TEAEs); serious TEAEs were reported in 5.5%, 6.4%, 2.8%, in PBO, combined UST and combined GUS, respectively. Death occurred in 1 patient (UST90mg q8wk) (suspected pulmonary embolism or thoracic aorta aneurysm). Infections were reported in 29.1%, 29.6%, and 22.9% in the PBO, combined UST, and combined GUS groups, respectively; serious infections occurred in 1 PBO patient (appendicitis), 1 UST 90mg q8wk-treated patient (UTI) and 2 GUS 200mg q8wk-treated patients (1 lobar pneumonia and 1 gastroenteritis). No TB, opportunistic infections, MI or stroke were reported. A serious TEAE of unstable angina was reported in PBO. There were 2 cases of malignancy: squamous cell carcinoma of lung in UST 90mg q12wk group and breast cancer in GUS 200mg q8wk.

Conclusions Neither UST nor GUS demonstrated significant efficacy in improving signs and symptoms of active RA based on ACR20 response at wk28. Improvements (based on nominal p<0.05) were observed in some secondary efficacy measures in both UST groups vs PBO. Both UST and GUS were generally well tolerated. Based on these results,inhibition of IL12 and/or IL23 does not appear to significantly alleviate signs and symptoms of active RA. These results provide additional insights into the differences between RA and psoriatic joint disease.

Disclosure of Interest J. Smolen Grant/research support from: Janssen Research & Development, LLC., S. Agarwal Grant/research support from: Janssen Research & Development, LLC., E. Ilivanova Grant/research support from: Janssen Research & Development, LLC., X. Xu Employee of: Janssen Research & Development, LLC., Y. Miao Employee of: Janssen Research & Development, LLC., S. Mudivarthy Employee of: Janssen Research & Development, LLC., W. Xu Employee of: Janssen Research & Development, LLC., W. Radziszewski Employee of: Janssen Research & Development, LLC., A. Greenspan Employee of: Janssen Scientific Affairs, LLC., A. Beutler Employee of: Janssen Research & Development, LLC., D. Baker Employee of: Janssen Research & Development, LLC.

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