gms | German Medical Science

Background: Upadacitinib (UPA) is an oral, selective JAK-1 inhibitor in development for the treatment of patients with moderate-to-severe rheumatoid arthritis (RA) and other immune-mediated diseases. SELECT-NEXT is a randomized, double-blind, placebo (PBO)-controlled Phase 3 trial in RA patients with an inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), in which UPA has shown significant improvements in clinical signs and symptoms compared with PBO [1]. One of the inclusion criteria was high sensitivity C-reactive protein (CRP) ≥3 mg/mL at screening. This is a post hoc analysis to determine the relationship between baseline CRP and clinical outcomes.

Methods: High-sensitivity CRP laboratory values were determined by central testing. Patients were categorized into quartiles by baseline CRP, with ranges (mg/L) of Q1: 0.2–4.6; Q2: 4.6–8.5; Q3: 8.5–17.7; Q4: 17.9–122.0. At Week 12, patient outcomes were summarized by baseline CRP quartiles in the three treatment arms (UPA 15 mg or 30 mg once daily [QD], or PBO).

Disease activity was measured by Disease Activity Score-28 with CRP (DAS28-CRP) and Clinical Disease Activity Index (CDAI) applying low disease activity (LDA) or remission criteria. Patient assessment of pain at 50/70% improvement levels was measured using a 0–100 mm visual analog scale. Statistical comparisons for UPA versus PBO in corresponding CRP quartiles were conducted using the Cochran–Mantel–Haenszel test. Non-responder imputation was applied for missing values.

Results: Baseline characteristics across 661 patients are displayed in Table 1 [Tab. 1]. There was a trend for higher measures of DAS28/CDAI/pain when comparing Q4 with Q1. However, CRP levels were well matched between treatment groups.

At Week 12, the percentage of patients achieving DAS28 LDA, DAS28 remission, and 50/70% improvement in pain was numerically similar across UPA-treatment CRP quartiles, and consistently significantly higher than in corresponding PBO CRP quartiles (Table 2 [Tab. 2]). There was a similar trend for more patients in the UPA-treatment quartiles to meet CDAI endpoints, although variable for statistical significance (Table 2 [Tab. 2]).

Conclusion: In SELECT-NEXT, RA patients treated with UPA demonstrated improvements in pain and disease activity, including achievement of remission irrespective of baseline CRP levels.

Disclosure of interest:

• Andreas Krause: Consultancies, speaking fees, or honoraria from AbbVie, Bristol-Myers Squibb, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, and UCB.
• David M Kofler: Research funding from Chugai Pharmaceutical Co., Ltd. and Bristol-Myers Squibb.
• Louis Bessette: Speaker, advisor, and research funding: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Merck, Novartis, Pfizer, and UCB.
• Christopher J Edwards: Has received honoraria and research support from AbbVie, Biogen, Bristol-Myers Squibb, Celgene, Fresenius, Janssen, Lilly, Mundipharma, Pfizer, MSD, Novartis, Roche, Samsung, Sanofi, and UCB.
• Filip Van den Bosch: Speaker and/or consultancy fees from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Sanofi, and UCB.
• Katya Cherny: No disclosures.
• Kirsten Famulla and Heidi S Camp: AbbVie employees, and may own AbbVie stock and/or options.
• Gerd R Burmester: Honoraria for consulting and lectures: AbbVie, Lilly, and Pfizer.

The study was funded by AbbVie. AbbVie participated in study design, data acquisition and interpretation, and in the writing, review, and approval of this abstract. Medical writing assistance was provided by Kevin Hudson, PhD, of 2 the Nth, which was funded by AbbVie Inc.