Abstract

Background: Among rheumatoid arthritis (RA) patients with chronic kidney disease (CKD), the usage of methotrexate and nonsteroidal anti-inflammatory drugs is limited1. Biologic Disease-Modifying Anti-Rheumatic Drugs (bDMARDs) may present potential alternatives. Objectives: The present study sought to investigate the real-world efficacy, safety, and tolerance of first-line bDMARDs in RA patients with CKD. Methods: We retrospectively analyzed the RA patients who had been prescribed their first bDMARDs at Toranomon Hospital or Toranomon Hospital Kajigaya between 2004 and 2022. Primary outcome was 36-month drug survival rate of first-line bDMARDs. Firstly, for the evaluation of overall effectiveness, safety, and tolerability, we compare the 36-month drug survival rates of bDMARDs across different modalities in three groups with CKD Stage G1, G2/G3a/G3b, and G4/G5. Secondly, for the assessment of effectiveness, we compare the trends of DAS28-CRP and DAS28-ESR over a period of six months following the initiation of bDMARDs. Thirdly, for the evaluation of safety, we investigate whether the proportion of reasons for discontinuation within 36 months varies according to the stage of CKD. Furthermore, as a sub-analysis exclusively focusing on CKD G4/G5, we compare and examine the 36-month retention rates between the dialysis and non-dialysis groups, as well as among different modalities of bDMARDs. Results: A total of 425 patients were enrolled, with 40 being under hemodialysis. The numbers of patients of CKD stage G1, G2/G3a/G3b, and G4/G5 were 165, 190, and 70, respectively. The first-line bDMARDs modalities included TNFα inhibitors (TNFαis) in 347 cases, interleukin-6 inhibitors (IL-6is) in 36 cases, and cytotoxic T-lymphocyte antigen-4 immunoglobulins (CTLA4-Igs) in 42 cases. The 36-month drug retention rates of bDMARDs stratified by CKD stages (G1, G2/G3a/G3b, and G4/G5) were as follows: TNFαi (42.9%, 43.4%, 34.0%), IL-6is (56.3%, 33.3%, 50.0%), and CTLA-4Igs (50.0%, 31.3%, 33.3%). Although no significant difference was captured, the retention rate of TNFαis was lower in the CKD stage G4/G5 group. Especially among patients with CKD stage G4/G5, the 36-month retention rates were as follows: non-dialysis (40.0%) and dialysis (42.5%), with no significant differences observed. Stratified by bDMARDs modality, the retention rates with IL-6is were significantly higher; TNFαis (34.0%), IL-6is (71.4%), and CTLA4-Ig (33.3%). Following the initiation of bDMARDs, RA activity assessed by DAS28-CRP and DAS28-ESR improved, enabling the reduction of PSL dose, irrespective of the patient's CKD stages. The most common reason for discontinuation was lack of effectiveness. Hazard ratio for discontinuation of IL-6i due to non-effectiveness in comparison to TNFαi was 0.48 (95%CI, 0.21 – 1.08), p = 0.08. Among patients with CKD stage G4/G5, the HR was 0.11 (95%CI, 0.02 – 0.85), p = 0.03. Conclusion: Our study provides initial evidence suggesting that first-line bDMARDs can be utilized effectively, safely, and tolerably in RA patients with CKD, even among patients on dialysis. In particular, IL-6i had a significantly higher drug retention rate in patients with CKD stage G4/G5 and fewer discontinuations due to ineffectiveness. REFERENCES: [1] Kameda H, Fujii T, Nakajima A, et al. Japan College of Rheumatology guideline for the use of methotrexate in patients with rheumatoid arthritis. Mod Rheumatol. 2019. Acknowledgements: NIL. Disclosure of Interests: None declared.