Background The optimal strategy to use biologic DMARDs (bDMARDs) after rituximab (RTX) in RA is unknown.
Objectives To evaluate the effectiveness of switching to alternative modes of action (i.e. tumor necrosis factor alpha inhibitor (TNFi), abatacept (ABA) or tocilizumab (TCZ)) after RTX discontinuation.
Methods Patients of the prospective, longitudinal and multinational CERERRA (European Collaborative Registries for the Evaluation of Rituximab in Rheumatoid Arthritis) database were analyzed with respect to the effectiveness of TNFi, ABA or TCZ as a new bDMARD after RTX. Patients were included, if they had stopped RTX no longer than 6 months prior to the new bDMARD, had a baseline visit within 21 days of commencement of the new bDMARD, and at least 1 follow up visit. Baseline characteristics were compared across bDMARD classes. The effectiveness of the new bDMARD was assessed by the decline in DAS28-ESR and CDAI after 6 months follow up. Multivariable linear regression was used to adjust for potential confounders. EULAR response rates after 6 months were compared for the treatments and drug discontinuation rates were calculated by the Kaplan-Meier method and compared across bDMARD classes.
Results The demographics and baseline disease characteristics as well as the use of concomitant methotrexate, leflunomide, or other sDMARDs were similar between the treatment groups.
At baseline, the median DAS28-ESR was 5.7 (IQR 4.8-6.6) among all patients and was similar across treatment groups (p=0.97). Patients on TCZ had a significantly greater decline of DAS28-ESR, than patients on TNFi or ABA after 6 months (Figure 1A). After adjusting for age, sex, baseline prednisone use and the number of previous bDMARDs, the average decline was 1.0 (95% CI 0.2-1.7) units smaller in patients on TNFi and 1.8 (95% CI 1.0-2.5) units smaller in patients on ABA compared to patients on TCZ.
The median CDAI in all patients was 25.1 (IQR 17.6-34.9) at baseline and was similar across the three treatment groups (p=0.41). The greatest decline was present in the TCZ group (Figure 1B). After adjusting for age, sex, baseline prednisone use and the number of previous bDMARDs, the average decline was 9.4 (95%CI 1.7-16.1) units smaller in patients on TNFi and 8.1 (95%CI 0.9-15.3) units smaller in patients on ABA compared to patients on TCZ.
Six months after the commencement of the new bDMARD, 34% of all subjects had a good EULAR response, 39% had a moderate response and 27% no response. The rates of EULAR responses varied significantly between treatment groups (p<0.001).
The HAQ-DI improved in all treatment groups (p<0.001), but did not differ between bDMARDs, as did drug retention rates.
Conclusions The results of this multinational cohort suggest that in clinical practice IL-6 blockade may be superior to alternative bDMARD classes following RTX discontinuation and represents a feasible strategy in the attainment of remission or low disease activity using a treat-to-target approach.
Disclosure of Interest U. Walker Consultant for: AbbVie, BMS, MDS, Pfizer, Roche, UCB, V. Jaeger: None declared, K. Chatzidionysiou: None declared, M. Hetland: None declared, E.-M. Hauge: None declared, K. Pavelka Consultant for: MSD, AbbVie, Pfizer, Roche, BMS, D. Nordström Consultant for: AbbVie, BMS, MSD, Pfizer, Roche, UCB, H. Canhao: None declared, M. Tomšič: None declared, R. van Vollenhoven Grant/research support from: AbbVie, BMS, GSK, Pfizer, Roche, UCB, Consultant for: AbbVie, Biotest, BMS, GSK, Janssen, Lilly, Merck, Pfizer, Roche, UCB, Vertex, C. Gabay Grant/research support from: Roche, Merck, Abbvie, Consultant for: Roche, Abbvie, Pfizer, BMS, Sanofi-Aventis, Merck, AB2 Bio