Background/Purpose: Treatment with tocilizumab (TCZ) monotherapy has been studied in 3 randomized clinical trials: AMBITION,¹ ACT-RAY,² and ADACTA.³ AMBITION¹  was the first trial to demonstrate clinical superiority of a biologic monotherapy over methotrexate (MTX) monotherapy: in pts who were MTX naive or MTX free for 6 mos before entry, treatment with TCZ 8 mg/kg monotherapy resulted in statistically greater ACR 20/50/70 responses than MTX at 24 wks. Numeric differences favoring TCZ monotherapy were observed for other endpoints and pt-reported outcomes as early as 2 wks. TCZ was generally well tolerated. In this post hoc exploratory analysis, long-term efficacy was evaluated in pts from AMBITION who remained on TCZ monotherapy in the ongoing long-term extension (LTE) period up to 240 wks. The rate, timing, and nature of the addition of disease-modifying anti-rheumatic drug (DMARD) for TCZ pts who added DMARDs were also characterized.

Methods: Pts randomized to TCZ 8 mg/kg monotherapy in AMBITION (n=286) who entered the LTE (n=243) were included. During the LTE period, MTX/other allowable DMARD could be added according to the investigator’s practice and as tolerated by the pt for those pts who did not achieve a 50% reduction in the number of tender and swollen joints from baseline of the core study. Efficacy assessments and DMARD status were evaluated up to 240 wks.

Results: Of 243 pts assigned to TCZ monotherapy who entered the LTE, 57.2% (n=139) remained on monotherapy in the LTE until withdrawal or data cut, 9.9% (n=24) added a DMARD before LTE entry, and 32.9% (n=80) added a DMARD after LTE entry (18.5% [n=45] ≤3 wks post-entry and 14.4% [n=35] >3 wks post-entry). Added DMARDs included MTX (93% [97/104]), hydroxychloroquine (3% [3/104]), leflunomide (2% [2/104]), and parenteral gold (2% [2/104]). Of the 139 pts who remained on TCZ monotherapy, 102 (73%) reached 240 wks of treatment for this data cut and 37 (27%) withdrew. Mean SJC, TJC, and DAS28 (data not shown) decreased sharply during the first 24 wks, and levels continued to decrease or were maintained thereafter (Table). Similar trends in improved disease state were observed, as shown by 40.1% and 16.7%  of pts achieving DAS28 <2.6 and clinical disease activity index (CDAI) remission by wk 24, respectively; rates increased or were maintained thereafter; absolute numbers achieving these endpoints increased to wks 192 and 120 (Table). Absolute numbers of pts achieving DAS28 ≤3.2 and CDAI low disease activity increased to wks 120 and 96 (data not shown for wk 96), respectively.

Conclusion: For the large proportion of pts continuing treatment in the LTE, TCZ monotherapy provided durable efficacy over time, as demonstrated by increasing proportions and/or numbers achieving low disease activity and remission thresholds.

References: 1. Jones Ann Rheum Dis 2010;69:88; 2. Dougados Ann Rheum Dis doi:10.1136/ annrheumdis-2011-201282; 3. Gabay EULAR 2012.