Background In Germany, Tocilizumab (TCZ) is used for the treatment of rheumatoid arthritis both in biologic-naïve patients and those with previous failures of biologic (b)DMARDs.
Objectives To investigate effectiveness and retention rates of TCZ in patients with multiple bDMARD failures.
Methods We included 885 RA patients enrolled with the start of TCZ treatment between 2009 and 2015 in the German biologics register RABBIT (Rheumatoid arthritis: Observation of biologic therapy). Patients were stratified according to the number of bDMARD failures prior to the initiation of TCZ: biologic naive (n=318), 1 bDMARD failure (n=286), 2 bDMARD failures (n=186), ≥3 bDMARD failures (n=95).
We used Kaplan-Meier survival methods to examine the retention rates within 12 months after the initiation. Discontinuation was defined as stopping TCZ therapy. Effectiveness regarding the control of disease activity (mean DAS28-ESR) over 3, 6 and 12 months was examined with linear mixed models.
Results Compared to biologic naive patients those with prior bDMARD failures at start of TCZ were younger but had significantly longer disease duration (bio-naive: 8, 1 bDMARD failure: 11.6, 2 failures: 13.3 and ≥3 failures: 15.3 years; p<0.01). The DAS28 at baseline and loss of physical function were significantly higher in patients with ≥3 bDMARD failures. In the latter group patients with more than 2 comorbidities were also more frequent (21% (bio-naive), 31% (1), 24% (2), 38% (≥3 failures)). No differences were found regarding concomitant use of glucocorticoids and csDMARDs. All patients with ≥3 bDMARD failures had been exposed to TNF-inhibitors (TNFi), 60% had also been exposed to other bDMARD classes. In contrast, only 5.9% (12.9%) of patients with 1 (2) bDMARD failures had been exposed to non-TNFi.
During follow-up in RABBIT, patients with ≤2 bDMARD failures reached low disease activity (DAS28) on average while those with ≥3 bDMARD failures remained in moderate disease activity. Treatment continuation on TCZ therapy was similar in biologic naive patients and in those with ≤2 bDMARD failures. Patients with ≥3 bDMARD failures had significantly lower continuation rates (Figure). Adverse events (AEs) were the most frequent reason for discontinuation in all strata; in patients with ≥3 bDMARD failures the withdrawal of TCZ due to AEs occurred in 52% of patients.
Conclusions TCZ was similarly effective in biologic naive patients and in patients with up to 2 prior TNFi failures. The majority of those patients achieved low disease activity (DAS28<3.2). However, in patients with ≥3 bDMARD failures disease activity remained on a higher level and treatment continuity was significantly lower. It seems that despite all progress in the treatment of RA during the last decades a small patient group remains in which the disease is difficult to be controlled despite effective treatment.
Disclosure Supported by a joint, unconditional grant from AbbVie, Celltrion, Hospira, Bristol-Myers Squibb, MSD Sharp&Dohme, Pfizer, Roche, and UCB.
Disclosure of Interest None declared