Background Monotherapy with a biological can offer an alternative treatment approach in RA patients (pts) for whom methotrexate (MTX) is not appropriate. In ACT-SURE, a phase 3b, 24-wk, prospective, open-label study in adult pts who had moderate to severe active RA and an inadequate response (IR) to current biological or non-biological DMARDs, tocilizumab (TCZ) monotherapy has shown safety and efficacy similar to those of TCZ+DMARD combination.1 However, it is unknown whether biological monotherapy is appropriate for TNF-IR pts, who often have more refractory disease.
Objectives To analyse safety and efficacy measures in pts who were TNF-IR and received TCZ monotherapy or TCZ+DMARDs in the ACT-SURE study.
Methods In ACT-SURE, pts at academic/non-academic centres and in private practice settings who were DMARD-IR or TNF-IR received TCZ 8 mg/kg every 4 wks, alone or in combination with 1 or more DMARDs at the investigator’s discretion. Analyses are presented in TNF-IR pts who received TCZ as monotherapy vs TNF-IR pts who received TCZ+DMARDs.
Results Of 1,681 evaluable pts in the study, 706 were TNF-IR. Of these, 173 pts received TCZ monotherapy and 532 received TCZ+DMARD. 63% of the monotherapy pts and 30% of the TCZ+DMARD pts were IR to ≥3 TNF inhibitors. In pts on TCZ+DMARD, the most commonly used DMARD was MTX (78%; median weekly dose 17.5 mg), followed by leflunomide (12%), hydroxychloroquine (11%) and sulphasalazine (10%). Baseline DAS28 was similar in both groups (6.3, 6.0). Safety in monotherapy/add-on DMARDs was: withdrawal, 16%/17%; adverse event (AE), 82%/81%; serious AE, 10%/9%; AE leading to withdrawal, 7%/6%; infection, 39%/40%; serious infection, 3%/2%; AE during infusion; 6%/7%; neutrophil decrease <1,000/mm3at least once, 1%/4%; ALT shift to >1.5× upper limit of normal (ULN) at any time point, 11%/15%; AST shift to >1.5× ULN at any time point, 2%/6%. At wk 24, efficacy end points were comparable between groups (Table).
Conclusions In a setting close to real life, TCZ monotherapy was highly efficacious at wk 24 in a refractory TNF-IR population and comparable to TCZ+DMARDs. The safety profile was similar for both groups. The results suggest that TCZ monotherapy offers clinical benefit in pts who cannot tolerate MTX or in whom MTX is not appropriate.
Sibilia J et al. Ann Rheum Dis 2011;70(suppl 3):466.
Disclosure of Interest A. Östör Consultant for: Roche, Chugai, Schering-Plough/MSD, Abbott, Wyeth/Pfizer, BMS, GSK, MerckSorono and UCB, J. Román Ivorra Consultant for: Pfizer, UMC, Actelion, J. Wollenhaupt Consultant for: Roche, Chugai, Speakers Bureau: Roche, Chugai, C. Mpofu Employee of: Roche, C. Bernasconi Consultant for: F. Hoffmann-La Roche Ltd, J. Sibilia Speakers Bureau: Roche, Chugai, V. Bykerk Grant/Research support from: Amgen, Pfizer, UCB, BMS, Roche, Abbott, Consultant for: Pfizer, BMS, UCB, Boehringer Ingelheim, Genentech