Background Tocilizumab (TCZ) is a humanized anti-IL-6 receptor-blocking monoclonal antibody used for the treatment of rheumatoid arthritis (RA), idiopathic juvenile arthritis (IJA) and off-label in Adult Onset Still Disease (AOSD). The development of anti-TCZ antibodies could reduce treatment efficacy or induce treatment failure.
Objectives To analyse TCZ serum levels and antidrug antibodies (ADA) in a cohort of RA, IJA and AOSD patients treated with TCZ, and to evaluate its relationship with Disease Activity Score using a 28-joint count (DAS28), C-reactive protein (CRP) levels and the presence of combined treatment with glucocorticoids or DMARDs.
Methods Cross-section study including all patients undergoing chronic treatment with TCZ in a tertiary academic hospital. Referral area: 850,000 inhabitants. Twenty-two patients were included. TCZ serum and ADA levels were measured by ELISA (Theradiag) at baseline (before infusion), 15 days and 30 days after infusion.
Results Twenty-two patients were studied: 18 RA, 3 IJA and 1 AOSD, 81.8% female; mean age and mean disease duration: 54.2 (±13) and 15.5 (±12) years respectively; 73% of the RA patients were positive for anti-CCP and 70% for rheumatoid factor, mean DAS28-CRP at day 0 and 30: 2.9 and 2.6 respectively. Fifteen patients were treated with TCZ for more than 1 year (range 12-58 months), 19 were treated with TCZ at 8 mg/kg, 2 at 6mg/kg, and one at 5mg/kg every 4 weeks due to low disease activity. Thirteen patients received TCZ in monotherapy, 9 received DMARDs combined treatment, 10 with glucocorticoids (mean dose 4mg/day, range 2-10mg). TCZ serum levels were at baseline: 1.2- 61.7 μg/ml, 15 days: <1-130.1 μg/ml and 30 days: <1-97.1 μg/ml. No patient showed presence of ADA. No correlation was found with DAS28-CRP, but there was inversely relation between CRP and TCZ serum levels (p=ns). The mean CRP levels were 14.4, 64.2 and 17.6 mg/dL at day 0, 15 and 30. TCZ Serum levels were higher in patients with combined therapy with DMARDs than those with monotherapy at day 15 and 30 (p=ns, 71 vs 55 μg/mL/23 vs 12 μg/mL, respectively). Patients treated without glucocorticoids had high levels of TCZ (68.62 vs 59.96 μg/mL at day 15 and 20.2 vs 13.68 μg/mL at day 30, p=ns)
Conclusions Levels of TZC were heterogeneous. Our patients showed no presence of ADA, this data suggest that TCZ has a low immunogenic potential. No correlation was found in disease activity and TCZ serum levels, but we found a relation with CRP levels. Patients with DAMRDs or without glucocorticoids showed higher levels of TCZ. We did not find correlation between combined treatment with DMARDs or glucocorticoids and levels of TCZ. Our study was limited due to a low sample size; we cannot exclude the correlation between TCZ and DAS28-CRP in a higher sample of patients.
Dougados M, Kissel K, Conaghan PG et al. Clinical, radiographic and immunogenic effects after 1 year of tocilizumab-based treatment strategies in rheumatoid arthritis: the ACT-RAY study. Ann Rheum Dis. 2014;73(5):803-9
Van Herwaarden N, Herfkens-Hol S, van der Maas A, et al. Dose reduction of tocilizumab in rheumatoid arthritis patients with low disease activity. Clin Exp Rheumatol. 2014;32(3):390-4
Disclosure of Interest None declared