Treatment With Anti–Tumor Necrosis Factor Biologic Agents in Human T Lymphotropic Virus Type I–Positive Patients With Rheumatoid Arthritis

Abstract

Objective. To investigate the response to and safety of anti-tumor necrosis factor (anti-TNF) therapy in human T lymphotropic virus type I (HTLV-I)-positive patients with rheumatoid arthritis (RA).Methods. Therapeutic response was evaluated in 10 HTLV-I-positive and 20 HTLV-I-negative patients with RA (sex and age matched) at 3 months after the beginning of anti-TNF therapy using the European League Against Rheumatism improvement criteria. As secondary end points, the discontinuation rate of anti-TNF therapy and its safety, especially the development of adult T cell leukemia (ATL), were evaluated over a 2-year period. Results. Significantly higher baseline levels of C-reactive protein (CRP) were observed in HTLV-I-positive patients than in HTLV-I-negative patients (P ‫؍‬ 0.0003). The response rate to anti-TNF therapy was lower in HTLV-I-positive patients than in HTLV-I-negative patients. The median CRP level, erythrocyte sedimentation rate, and Disease Activity Score in 28 joints at 3 months after anti-TNF treatment in HTLV-I-positive patients were significantly higher than in HTLV-Inegative patients (P ‫؍‬ 0.003, P ‫؍‬ 0.03, and P ‫؍‬ 0.003, respectively). The discontinuation rate due to insufficient response was significantly higher in HTLV-I-positive patients than in HTLV-I-negative patients (P ‫؍‬ 0.013). During the 2-year observation period, no patients developed ATL. Conclusion. These data suggest that HTLV-I-positive patients with RA had higher inflammation and greater resistance to anti-TNF treatment than HTLV-I-negative patients. Further study is necessary to determine whether HTLV-I infection should be measured when anti-TNF agents are administered to patients with RA, especially in areas were HTLV-I is endemic.

Inflammatory manifestations of HTLV-1 and their therapeutic options

“…There is always the worry of ATLL development if immune-modulatory drugs, such as TNF-a, which are standard treatment for RA, are used. There are reassuring reports on TNF-a blockers, although it seems to be less effective in HTLV-1 positive patients [207,208]. Rituximab and etanercept have been used [209], but need to be verified in clinical trials.…”

Brief Report: Attenuated Effectiveness of Tumor Necrosis Factor Inhibitors for Anti–Human T Lymphotropic Virus Type I Antibody–Positive Rheumatoid Arthritis

“…The HTLV‐I virus infects primarily CD4+ T lymphocytes but also synovial fibroblasts and salivary gland epithelial cells, and HTLV‐I infection can modify the functions of these cells . In this context, a previous study by our group that was conducted in an area endemic for HTLV‐I infection showed that HTLV‐I – positive patients with RA are more resistant to TNF inhibitors compared with HTLV‐I – negative RA patients .…”

“…In a previous study by our group , we compared the response to TNF inhibitors in 10 HTLV‐I–positive RA patients with that in 20 HTLV‐I–negative patients with RA (matched for age and sex), in a single area with a high prevalence of HTLV‐I, Miyazaki Prefecture. We observed that the treatment outcomes were generally affected by several background elements, such as disease activity at the start of treatment and positivity for rheumatoid factor (RF) or anti–citrullinated protein antibodies (ACPAs).…”

HTLV‐1 carrier psoriasis patients treated by anti‐IL‐23/IL‐17

“…They showed no indication of developing ATLL during a 2-year observation period. 2 Furthermore, HTLV-1-infected cells from patients with HTLV-1-associated myelopathy showed no significant inflammatory cytokine profiles by anti-tumour necrosis factor-a inhibitor. 3 These findings suggest that the inhibition of anti-tumour necrosis factor-a has no influence on the development of ATLL.…”