2109: Domains Contributing to Minimal Disease Activity Non-Achievement in Patients with Psoriatic Arthritis Receiving Golimumab: Post Hoc Analysis of a Phase 3, Randomized, Double-blind, Placebo-controlled Study

Arthur Kavanaugh¹, Gordon Lam², Lai-shan Tam³, Natalie Shiff⁴, Youngja Lee⁵, Ana-Maria Bravo Perdomo⁶, May Shawi⁷, Elizabeth Hsia⁸, Emmanouil Rampakakis⁹ and Carlos Enrique Toro Gutiérrez¹⁰, ¹University of California San Diego, La Jolla, CA, ²Arthritis and Osteoporosis Consultants of the Carolinas; Clinical Affiliate, Atrium Health and the Wake Forest School of Medicine, Cornelius, NC, ³The Chinese University of Hong Kong, Hong Kong, China, ⁴Janssen Scientific Affairs, LLC, Horsham, PA, USA/ Department of Community Health and Epidemiology, College of Medicine, University of Saskatchewan, Saskatoon, Canada, Philadelphia, PA, ⁵Immunology Medical Affairs, Janssen Asia Pacific, Yongsan-gu, Seoul, Republic of Korea, ⁶Immunology Medical Affairs, Janssen Latin America, Columbia, Colombia, ⁷Immunology Global Medical Affairs, Janssen Pharmaceutical Companies of Johnson & Johnson, Horsham, PA, ⁸Janssen Research and Development, LLC; University of Pennsylvania School of Medicine, Kennett Square, PA, ⁹McGill University, Department of Pediatrics and JSS Medical Research, Montréal, QC, Canada, ¹⁰Internal Medicine and Rheumatology, Reference Center for Osteoporosis, Rheumatology & Dermatology. Pontificia Javeriana University, Calí, Colombia

Background/Purpose: Sustained minimal disease activity (MDA) is only achieved by a small portion of PsA patients (pts). Levels of disease activity consistent with MDA may be achieved less frequently in pt-driven domains¹. Here we identified PsA disease domains contributing to MDA non-achievement and associated factors using data from the Phase 3 GO-VIBRANT trial.

Methods: GO-VIBRANT included biologic-naïve pts with active PsA (≥5 swollen [SJC] & ≥5 tender joints [TJC], CRP ≥0.6 mg/dL) despite standard therapies. Pts were randomized 1:1 to intravenous golimumab (IV-GLM) 2 mg/kg at weeks (W) 0, 4, and then Q8W through W52; or IV placebo (PBO) at W0, 4, 12, and 20 followed by crossover to IV-GLM at W24. This post hoc analysis included 241 IV-GLM-treated pts. MDA requires fulfillment of ≥5/7 criteria: TJC ≤1, SJC ≤1, Psoriasis Area and Severity Index (PASI) ≤1, Pt Pain ≤15mm, Pt Global Assessment (PtGA) ≤20mm, Health Assessment Questionnaire – Disability Index (HAQ-DI) ≤0.5, and ≤1 tender entheses. A trajectory of achieving each MDA criterion through W52 was built using non-responder imputation for missing values. Time to achieving each criterion was assessed with Kaplan-Meier analysis; to account for differences in scales and criteria strictness, a secondary analysis utilized scores normalized to the SJC (0-66) scale and set targets to ≤1. MDA predictors were assessed with multivariate regression for time to achievement (Cox proportional hazards) and W52 achievement (logistic). Presence of a proxy for central pain sensitization/fibromyalgia (pFM) was defined as TJC minus SJC ≥7².

Results: IV-GLM treatment was associated with improvement in all MDA domains, with W24 & W52 response rates of: SJC (53.5% & 61.8%), TJC (22.8% & 32.4%), PASI (53.6% & 59.7%), Pt Pain (37.3% & 43.6%), PtGA (44.8% & 45.2%), HAQ-DI (37.8% & 44.9%), entheseal points (68.4% & 64.6%). Time to achieve minimal SJC and enthesitis was significantly faster than TJC, HAQ-DI, and Pt Pain for native-scale scores (Fig). When normalized, TJC, HAQ-DI, and Pt Pain, as well as PtGA, were slower to respond. Higher baseline (BL) TJC and pFM were significant predictors of longer time to achieve TJC ≤1 and of not meeting TJC ≤1 at W52 (Table). Significant BL predictors of longer time to achieve HAQ-DI ≤0.5 were higher age, HAQ-DI score, and spinal pain; these as well as smoking were associated with lower odds of HAQ-DI ≤0.5 at W52. Worse BL pain, pFM, and higher BMI were significant predictors of longer time to achieve Pt Pain ≤15 mm and non-achievement at W52. Worse BL PtGA (only for time to achievement) and smoking status were negative predictors of PtGA ≤20mm.

Conclusion: IV-GLM provided improvement in each MDA domain through W52. Although IV-GLM was effective across most variables assessed, BL domain score, pFM presence, older age, and modifiable lifestyle factors (smoking, higher BMI) were negative determinants of MDA in the slower to respond pt-driven domains. Addressing these modifiable factors may optimize MDA achievement in PsA.

References:
1. Rahman et al. BMJ Open 2017; 7 (8): e016619.
2. Pollard et al. Rheumatology. 2010 May;49(5):924-8.


Disclosures: A. Kavanaugh, AbbVie, Amgen, Pfizer, Bristol-Myers Squibb(BMS), Centocor-Janssen, UCB, AstraZeneca, Roche; G. Lam, AbbVie, Bristol-Myers Squibb(BMS), Janssen, Pfizer, Sanofi, UCB; L. Tam, AbbVie, Amgen, Boehringer-Ingelheim, Eli Lilly, GlaxoSmithKlein(GSK), Janssen, Novartis, Pfizer, Sanofi, AstraZeneca; N. Shiff, Janssen Scientific Affairs, LLC, Johnson & Johnson, AbbVie, Gilead; Y. Lee, Janssen, Johnson & Johnson; A. Bravo Perdomo, Janssen, Johnson & Johnson; M. Shawi, Janssen Pharmaceutical Companies of Johnson and Johnson; E. Hsia, Janssen Research and Development, LLC, Johnson & Johnson; E. Rampakakis, Janssen, JSS Medical Research; C. Toro Gutiérrez, AbbVie, Amgen, Biopas, Bristol-Myers Squibb(BMS), Boehringer-Ingelheim, Janssen, Pfizer, Roche, Novartis.