Background TCZ monotherapy has been studied in 3 global randomised clinical trials: AMBITION,1 ACT-RAY2 and ADACTA.3 The AMBITION trial demonstrated statistically significant superiority of a biologic monotherapy over MTX monotherapy; in pts who were MTX naive or MTX free for 6 mos prior to study start, TCZ 8 mg/kg monotherapy resulted in statistically greater ACR20/50/70 responses at 24 wks compared with MTX.
Objectives In this post hoc exploratory analysis, efficacy and safety were evaluated in pts from AMBITION who remained on TCZ monotherapy in the long-term extension (LTE) study up to 240 wks.
Methods Pts randomised to TCZ 8 mg/kg monotherapy in AMBITION (n=286) who entered the LTE (n=243) were included. During the LTE, MTX/other allowable disease-modifying anti-rheumatic drug (DMARD) could be added for pts who did not achieve a 50% reduction in number of tender and swollen joints from baseline of the core study. The rate, timing and nature of added DMARDs were characterised. Efficacy and adverse events (AEs) were also assessed up to 240 wks.
Results Of 243 pts who entered the LTE, 57.2% (n=139) remained on monotherapy 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; 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 and 37 (27%) withdrew. Mean SJC, TJC and DAS28 (data not shown) decreased sharply during the first 24 wks and continued to decrease or were maintained thereafter (Table). Similar trends in improved disease state were observed; 40.1% and 16.7% of pts achieved DAS28 <2.6 and clinical disease activity index (CDAI) remission, respectively, by wk 24; rates increased or were maintained thereafter; absolute numbers achieving these endpoints increased to wks 192 and 120 (Table). Absolute numbers achieving DAS28 ≤3.2 and CDAI low disease activity increased to wks 120 and 96 (data not shown for wk 96), respectively. AEs for all pts in this analysis (n=243) were consistent with the known safety profile of TCZ.
Conclusions For pts who stayed on monotherapy during the trial, TCZ treatment provided durable efficacy over time, as demonstrated by increasing proportions and/or numbers achieving low disease activity and remission thresholds. AEs reported were consistent with the known safety profile of TCZ; no new safety signals were detected.
Ann Rheum Dis 2010;69:88;
Ann Rheum Dis 2013;72:43;
Ann Rheum Dis 2012;71(Suppl3):152
Disclosure of Interest: G. Jones Grant/research support from: Abbott, Roche, Novartis, Amgen, MSD, Auxilium, UCB, Consultant for: Abbott, Roche, Novartis, Amgen, MSD, UCB, Janssen, Genzyme, Speakers bureau: Abbott, Roche, Novartis, Amgen, MSD, UCB, Janssen, A. Sebba Consultant for: Genentech, Lilly, Novartis, Merck, Speakers bureau: Genentech, Novartis, A. Anisfeld Employee of: Genentech, a member of the Roche group, J. Devenport Employee of: Genentech, a member of the Roche group, C. Bernasconi Consultant for: Roche, D. Smart Employee of: Roche, D. Galindez Employee of: Genentech, a member of the Roche group, C. Mpofu Employee of: Roche, J. Gomez-Reino Grant/research support from: MSD, UCB, Consultant for: BMS, GSK, MSD, Pfizer, Roche, UCB, Speakers bureau: Abbott, BMS, GSK, MSD, Pfizer, Roche, UCB