Background Clinical trials have demonstrated the efficacy of Tocilizumab (TCZ) for patients with rheumatoid arthritis (RA). Several studies have demonstrated that dose tapering of TNF-inhibitors is a feasible therapeutic option in rheumatic patients with low disease activity (LDA). Nevertheless, few reports analyse the effectiveness of dose-tapering of TCZ.
Objectives To evaluate the clinical outcome and incidence of flares in patients with RA in remission or LDA under a tapering strategy with TCZ and to analyse the influence of the tapering on serum drug levels.
Methods Of a cohort of 34 adult patients with RA under therapy with TCZ, 13 patients with sustained LDA or remission (DAS 28-ESR <3,2) under a tapering strategy were included. Clinical disease activity (DAS-28-ESR, CDAI and SDAI), serological data (C-reactive protein, erythrocyte sedimentation rate) and serum TCZ levels were evaluated at the visit prior to starting tapering strategy (V0) and at the last visit available during a three-year follow-up period (LV). The tapering strategy consisted in a progressive interval prolongation and/or dose reduction. A flare was defined as an increase of the DAS28 greater than 3.2 plus a delta-DAS28 (related to pre-tapering DAS28) lower than -0.6. The number of flares, time to first flare and the activity in the worst flare were collected. In the case of a flare, the concomitant therapy and TCZ dose could be intensified. Blood samples were collected just before the infusion and serum drug levels were measured by ELISA.
Results The baseline demographic and clinical characteristics are shown in Table 1. No differences in the clinical activity (DAS28: 2,28± 0,8 at V0 vs 2,5±0,7 at LV, p=0,25; CDAI 4,71: ±5,1 at V0 vs 5,71±5,1 at LV p=0,08; SDAI (4,99±5,3 at V0 vs 5,0 ±4,8 at LV, p=0,052), number of swollen joints (1,69±3,2 at V0 vs 1,46±1,8 at LV; p=0,091) and tender joints (0,69± 1,1 at V0 vs 0,62±0,96 at LV; p=0,243) and acute-phase reactants (CRP: 0,48±0,6 at V0 vs 0,54±0,6 at LV, p=0,219; ESR: 7,69±3,1 at V0 vs 10,3±5,4 at LV, p=0,152) between V0 and LV were observed. The decrease of drug levels between V0 and LV was not significant (15,4±9,31 vs 3,02±5,99, p=0,867). During the follow-up period, 6 (43%) patients presented flares. The number of flares after the tapering strategy was 1,2±1,6 and the time to the first flare was 1±0,4 years. The following clinical and disease activity data and serum TCZ levels were registered at the worst flare: STJ: 6,7± 7,4 and TJC: 1,83±1,2; DAS28: 3,99±0,6, CDAI: 14,7± 8,2 and SDAI: 14,5±9,08; TCZ levels: 0,86±1,78. Most patients after having a flare (4/6) reached remission or LDA at the end of the study, and no significant differences in LDA were observed between those with or without flares (DAS-28 LV<3,2:4/11 (36,4%) vs 7/11 (63,6%), p=0,097; CDAI LV <10: 4/10 (66,7%) vs 6/10 (85,7%), p=0,42; SDAI LV <11: 4/11 (36,4%) vs 7/11 (63,6%), p=0,097, respectively). All of the patients continued on tapering strategy and no patients dropped out because of inefficacy.
Conclusions The tapering strategy in patients with RA with LDA or remission receiving TCZ appears to be feasible, resulting in a low proportion of patients with flares and a good longterm clinical disease activity control.
Disclosure of Interest C. Tornero Grant/research support from: Funded by an unrestricted medical grant from Pfizer., C. Plasencia: None declared, D. Pascual: None declared, T. Jurado: None declared, I. Monjo: None declared, M. B. Paredes: None declared, E. Moral: None declared, A. Pieren: None declared, L. Nuño: None declared, G. Bonilla: None declared, D. Peitedo: None declared, E. M.Mola: None declared, A. Balsa: None declared