Background We reported that human T-lymphotropic virus type 1 (HTLV-1) positive patients with rheumatoid arthritis (RA) had higher inflammation and greater resistance to anti-TNF treatment than HTLV-1 negative patients (1). Six of ten HTLV-1 positive patients with RA showed inadequate response to anti-TNF therapies (1).

Objectives To investigate the cytokine profile in peripheral blood of HTLV-1 positive RA patients, and to evaluate the response to and safety of anti-IL-6 receptor antibody, tocilizumab (TCZ) for HTLV-1 positive RA patients who were not responsive to anti-TNF treatments.

Methods We retrospectively evaluated 124 Japanese patients with RA, who were treated with anti-TNF therapies as first biologic agents in our cohort (1). Plasma samples were obtained from 8 of 10 HTLV-1 positive and 16 sex-age matched HTLV-1 negative RA patients before administration of anti-TNF therapies in our cohort. The levels of 25 cytokines in plasma were measured using multiplex cytokine assay (Luminex). Six of ten HTLV-1 positive RA patients were not responsive to anti-TNF treatments in our previous study (1). Then, five of six these RA patients were administered TCZ treatment as their secondary biologics. Therapeutic response at 3 months after beginning of treatment with TCZ was evaluated using EULAR response criteria. We also analyzed the changing of inflammatory biomarkers such as C-reactive protein (CRP), erythrosedimentation rate (ESR), disease activity score in 28 joints (DAS28) and clinical disease activity score (CDAI). As secondary endpoints, discontinuation rate of TCZ treatment and safety, especially the development of adult T-cell leukemia (ATL), were evaluated over a one-year period.

Results Significantly higher baseline levels of plasma CCL20 were observed in 8 HTLV-1 positive RA patients than that in 16 HTLV-1 negative RA patients (p=0.02). The levels of plasma IL-6 in 8 HTLV-1 positive RA patients showed the trend to be higher than that in 16 HTLV-1 negative RA patients (p=0.05). According to EULAR response criteria, the rate of good, moderate and no response in 5 HTLV-1 positive patients who were not responsive to anti-TNF therapies after treatment with TCZ was 60, 40, and 0%, respectively. The rate of low disease activity was 60%. The levels of CRP, ESR, DAS28, and CDAI in 5 HTLV-1 positive RA patients were significantly decreased at 3 months after treatment with TCZ (p=0.04, p=0.04, p=0.04 and p=0.04, respectively). The efficacy of TCZ treatment in these RA patients were sustained for at least one-year period. During the one-year observation period, no patients developed ATL.

Conclusions These data suggested that HTLV-1 positive RA patients might indicate different cytokine profile compared to HTLV-1 negative patients. Although HTLV-1 positive RA patients demonstrated resistance to anti-TNF therapies (1), TCZ treatment was effective and safe in these patients. It is possible that IL-6 may play an important role in the pathogenesis of HTLV-1 positive RA patients. Further study is necessary to clarify the role of HTLV-1 infection in the pathogenesis of RA.

References

1. Umekita K, et al. Treatment with anti-tumor necrosis factor biologics in human T-lymphotropic virus type 1 positive patients with rheumatoid arthritis. Arthritis Care Res. 2014; 66(5):788-92

Disclosure of Interest None declared