SAT0128 A PHASE 4 TRIAL ASSESSING THE IMPACT OF RESIDUAL INFLAMMATION AND CLINICAL CHARACTERISTICS ON THE OUTCOME OF DOSE TAPERING OF ADALIMUMAB IN PATIENTS WITH RHEUMATOID ARTHRITIS WHO ARE IN STABLE CLINICAL REMISSION
Authors: Paul Emery, Gerd Rüdiger Burmester, Esperanza Naredo, Ivan Lagunes-Galindo, Franziska Koenigsbauer, Philip G. Conaghan
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> For rheumatoid arthritis (RA) pts in stable clinical remission (SCR) on bDMARDs, EULAR and ACR recommend to consider tapering the dose of bDMARD.<sup>1,2</sup> However, there are limited data indicating which factors, if any, are prognostic of flares after tapering. Moreover, association between underlying inflammation and disease flare following tapering remains unclear. <h3>Objectives</h3> Investigate association between residual disease activity at double-blind(db) bl detected by MRI and occurrence of flares in SCR RA pts randomized to an adalimumab (ADA) dose tapering regimen controlled by ADA withdrawal (w/d). <h3>Methods</h3> Pts in SCR (DAS28[ESR or CRP] &lt;2.6) for at least 6 mos and at screening (DAS28[ESR] &lt;2.6) on ADA 40 mg eow were enrolled in this phase 4, randomized, db, parallel group study. Following 4-wksof open-label lead-in (OL-LI) during which SCR was confirmed, pts were randomized 5:1 to taper (ADA 40 mg q3w) and w/d arms for 36 wks. Pts experiencing flare (defined as either DAS28[ESR] &gt;2.6 and DAS28[ESR] increase &gt;0.6 from bl or DAS28[ESR] increase ≥1.2 from bl, irrespective of absolute DAS28[ESR]) received rescue OL ADA 40 mg eow for up to 16 wks. The primary endpoint was the association between bl hand and wrist synovitis and bone marrow edema (BME) RAMRIS scores and their composite with flare occurrence. Secondary endpoints were association between pt and disease characteristics and occurrence of flare, time to and occurrence/severity of flares, maintenance of remission, and time to and regain of clinical remission following flare. Logistic regression, descriptive statistics (counts and proportions with 95% CI) and Kaplan-Meier estimates are provided. Last observation carried forward was used for missing data. Treatment-emergent adverse events were monitored. <h3>Results</h3> Of 146 pts who entered the OL-LI period, 122 were in SCR at wks 0 and 4 and were randomized to taper (n=102) or w/d (n=20) arm. Pts were female (75%) with ∼13 yrs of active disease, received ADA for &gt;5 yrs (∼2 yrs in SCR). Bl disease activity measures were low (DAS28[ESR]: 1.7; composite synovitis and BME RAMRIS score: 4.0), and &gt;85% pts were in CDAI and/or SDAI remission. In the taper and w/d arms, 37 (36%) and 9 (45%) pts experienced flare, respectively. Time to flare was 18.0/13.3 wks (Q1 for taper/withdrawal arm). At wks 12/24/36, flare rates were 13.1/27.4/34.9% in the taper arm and 10.0/35.0/40.0% in the w/d arm. Neither of the bl RAMRIS scores nor their composite was associated with flare occurrence in the taper arm (<b>Table</b>). Only bl HAQ-DI was associated with flare occurrence. Through 16 wks of OL rescue with ADA 40 mg eow, 38% and 50% of pts in the taper and w/d arms, respectively, regained clinical remission; approximately 85% in both arms were in clinical remission by DAS28(ESR) &lt;2.6 at week 40. No new serious risks or safety signals were identified. <h3>Conclusion</h3> A relatively low flare rate was observed among this established RA population in longstanding SCR who tapered or withdrew ADA. Baseline HAQ-DI, but not MRI inflammation, was found to be associated with flare occurrence, which may be reflective of the very low bl MRI inflammation scores in this sustained remission cohort. <h3>References</h3> [1] Smolen, et al. Ann Rheum Dis, 2017;76:1113-36. [2] Singh, et al. Arthritis Rheumatol, 2016;68:1-26. <h3>Acknowledgement</h3> AbbVie, Inc: study sponsor, study design, data collection, analysis, interpretation, writing, review, approval of final version. Support: Maja Hojnik, MD, PhD. Writing: Dalia Majumdar, PhD, Benjamin Wolfe, PhD, Abbvie. Stats: Xiaolei Leahy, Abbvie. <h3>Disclosure of Interests</h3> Paul Emery Grant/research support from: Pfizer, MSD, AbbVie, Bristol-Myers Squibb, Roche, Consultant for: Pfizer, MSD, AbbVie, Bristol-Myers Squibb, UCB, Roche, Novartis, Gilead,Samsung, Sandoz and Lilly, Gerd Rüdiger Burmester Consultant for: Roche, Sanofi-Genzyme, Speakers bureau: Roche, Sanofi-Genzyme, Esperanza Naredo Consultant for: Abbvie, Speakers bureau: AbbVie, Roche, Bristol-Myers Squibb, Pfizer, UCB, Lilly, Novartis, Janssen, and Celgene GmbH, Ivan Lagunes-Galindo Shareholder of: AbbVie Inc, Employee of: AbbVie Inc, Franziska Koenigsbauer Shareholder of: AbbVie Inc, Employee of: AbbVie Inc, Philip G Conaghan Consultant for: Flexion Therapeutics, AbbVie, Medivir, Merck Serono, Novartis, GlaxoSmithKline