Background/Purpose:  Renal involvement is relatively common in rheumatoid arthritis (RA) patients. Recent randomized controlled trials of anti-tumor necrosis factor-α (anti-TNFα) showed that the concomitant administration of methotrexate (MTX) is superior to monotherapy. However, the dose of MTX must be reduced in RA patients with chronic renal insufficiency (CRI) because MTX elimination is delayed in these patients. In contrast, the ACT-RAY trials indicated that the efficacy of tocilizumab (TCZ) monotherapy is comparable with combination therapy with MTX. The present study was intended to evaluate the efficacy and safety of TCZ therapy in RA patients with CRI.

Methods: The subjects were all patients with RA who had started TCZ therapy at our hospital from April 2008 to December 2013. Pretreatment characteristics were compared between patients with and without CRI. Clinical disease activity index (CDAI) levels and hemoglobin values as well as adverse events were recorded during the follow-up period of the first 24 weeks. CRI was defined as an estimated glomerular filtration rate (eGFR) < 60 ml/min for 3 months.

Results: A total of 105 patients were included in this study and among these, 37 patients (35.2%) were diagnoses with CRI. Mean eGFR levels in the CRI group and in non-CRI group were 43.7 ml/min and 80.9 ml/min, respectively. Sixty percent of CRI patients and 70% of non-CRI patients were refractory to anti-TNFα agents. CRI patients were significantly older (75.3 years versus 62.0 years, p < 0.0005) and had longer RA duration (9.8 years versus 5.4 years, p = 0.005). There was no significant difference in the other RA-related markers between both groups. Approximately 85% of patients in each group showed high or median disease activity. Biopsy-proven amyloidosis was observed in one patient in the CRI group. Hypertension was observed at a significantly higher rate in the CRI group (81% versus 36.8%, p < 0.0005). Of note, serum levels of hemoglobin were significantly lower in CRI patients compared with non-CRI patients (11.2 g/dl versus 12.5 g/dl, p < 0.0005). Eighty-one percent of CRI patients received TCZ monotherapy, while 49% of non-CRI patients used MTX concomitantly with TCZ. Mean changes of CDAI at week 24 from baseline were 17.1 (26.7 to 9.6) in the CRI group and 17.5 (25.8 to 8.3) in the group without CRI. Rates of patients with low disease activity or remission at week 24 were 62.2 % of CRI patients and 55.9% of non-CRI patients. Mean hemoglobin levels were significantly increased over time during TCZ therapy. At week 24, mean increases of 1.2 g/dl (11.2 to 12.4, p < 0.0005) and 0.8 g/dl (12.5 to 13.3, p = 0.005) were observed in the CRI group and in the non-CRI group, respectively. Adverse events occurred in two patients without CRI (diverticulitis and acute cholecystitis). Neither serious adverse event nor aggravation of renal function was reported in the CRI group.

Conclusion: TCZ therapy was effective in reduction of disease activity and improvement of hemoglobin levels in RA patients with CRI. In addition, TCZ showed stable safety and tolerability profiles even in CRI patients.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/tocilizumab-therapy-for-rheumatoid-arthritis-patients-with-chronic-renal-insufficiency/