BENEFIT OF CONTINUING TOCILIZUMAB THERAPY (8 MG/KG EVERY 4 WEEKS) IN RHEUMATOID ARTHRITIS PATIENTS WHO HAVE NOT RESPONDED ADEQUATELY WITHIN THE FIRST 8 WEEKS

Background: Some patients (pts) with rheumatoid arthritis (RA) achieve rapid response to treatment with biologic agents, but those who do not respond early may still reach clinical response if treatment is continued. Objectives: To determine whether pts who did not respond adequately to tocilizumab (TCZ) by 8 wks (based on <50% improvement in SJC) achieved responses at later time points. Methods: This was a post hoc, exploratory analysis in pts from a phase 3 clinical trial (RADIATE) with previous inadequate responses to tumor necrosis factor-α inhibitors (TNF-IR). Pts were randomized to TCZ (4 [TCZ4], 8 [TCZ8] mg/kg) or placebo (control [Con]) every 4 wks plus weekly MTX. Wk 24 clinical responses including DAS28 improvement ≥1.2, low disease activity (LDAS [DAS28 ≤3.2]), DAS28 <2.6, and low CDAI (≤10) were assessed for patients who did not achieve ≥50% improvement in SJC from baseline by wk 8. Each end point was also assessed at wk 24 in pts who had not achieved that end point by wk 8. Missing joint counts were imputed with LOCF, while other components were not imputed. For each end point, pts who received rescue medication or had missing data were included in the analysis and counted as nonresponders. Results: The analysis included 158 Con pts, 161 TCZ4 pts, and 170 TCZ8 pts. By wk 8, ≥50% improvement in SJC was achieved by 49.4%, 50.3%, and 34.8% of TCZ8, TCZ4, and Con pts, respectively. By wk 8, a higher proportion of TCZ8 pts, followed by TCZ4 and Con pts, achieved DAS28 improvement ≥1.2 (81.2%, 55.3%, 24.7%), LDAS (20.0%, 4.3%, 0.6%), DAS28 <2.6 (11.2%, 0.6%, 0%),and CDAI ≤10 (13.5%, 5.6%, 5.1%). Among TCZ8 pts not achieving ≥50% improvement in SJC by wk 8, substantial proportions achieved DAS28 improvement, LDAS, DAS28 <2.6, and CDAI ≤10 at wk 24 (Table). In contrast, small proportions of TCZ4 pts not responding by wk 8 were able to achieve clinical responses at wk 24; little benefit was seen in Con pts. Similar patterns at wk 24 were seen in pts who did not achieve the higher bar of ≥50% improvement in both TJC and SJC by wk 8. Of pts who did not achieve each end point (ie, LDAS, DAS28 <2.6, CDAI ≤10) by wk 8, substantial proportions on TCZ8 but few on TCZ4 went on to achieve that end point at wk 24. Wk 24 Clinical Responses in pts Not Achieving ≥50% Improvement in SJC by Wk 8 End PointsPlacebo (Con) + MTXTCZ4 + MTXTCZ8 + MTX n=103n=80n=86 Improvement in DAS28 ≥1.2, n (%)7 (6.8)28 (35.0)46 (53.5) LDAS, n (%)1 (1.0)4 (5.0)21 (24.4) DAS28 <2.6, n (%)1 (1.0)2 (2.5)10 (11.6) CDAI ≤10, n (%)1 (1.0)4 (5.0)13 (15.1) Conclusions: In TNF-IR pts receiving TCZ who did not achieve at least 50% improvement in SJC by wk 8, very few (5.0%) pts in the 4 mg/kg group, but a substantial proportion of pts (24.4%) in the 8 mg/kg group, went on to achieve low disease activity status at wk 24 with continued treatment using the same dose. Clinicians might consider escalating TCZ dose to 8 mg/kg in pts receiving 4 mg/kg who do not show ≥50% in SJC by wk 8. Disclosure of Interest: E. Keystone Consultant for: Roche Pharmaceutical, S. Ogale Employee of: Genentech, J. Devenport Employee of: Genentech, D. Lepley Employee of: GenentechCitation: Annals of the Rheumatic Diseases, volume 70, supplement 3, year 2011, page 461Session: Rheumatoid arthritis – other biologic treatment (Poster Presentations )