Yayoi Hashiba

Treatment with anti–tumor necrosis factor biologic agents in human T lymphotropic virus type I–positive patients with rheumatoid arthritis.

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).

Comparative risk of hospitalized infection between biological agents in rheumatoid arthritis patients: A multicenter retrospective cohort study in Japan

Objective Knowing the risk of hospitalized infection associated with individual biological agents is an important factor in selecting the best treatment option for patients with rheumatoid arthritis (RA). This study examined the comparative risk of hospitalized infection between biological agents in a routine care setting. Methods We used data for all RA patients who had first begun biological therapy at rheumatology divisions of participating community hospitals in Japan between January 2009 and December 2014. New treatment episodes with etanercept, infliximab, adalimumab, abatacept, or tocilizumab were included. Patients were allowed to contribute multiple treatment episodes with different biological agents. Incidence rates (IRs) of hospitalized infection during the first year of follow-up were examined. Cox regression analysis was used to calculate hazard ratios (HRs) for overall hospitalized infection and for pulmonary hospitalized infection, adjusting for possible confounders. Results A total of 1596 new treatment episodes were identified. The incidence of overall hospitalized infection during the first year was 86 with 1239 person-years (PYs), yielding a crude IR of 6.9 per 100 PYs (95% confidence interval [CI], 5.6–8.6). After correction for confounders, no significant difference in risk of hospitalized infection was observed between treatment groups: adjusted HRs (95% CI) were 1.54 (0.78–3.04) for infliximab, 1.72 (0.88–3.34) for adalimumab, 1.11 (0.55–2.21) for abatacept, and 1.02 (0.55–1.87) for tocilizumab compared with etanercept. Patient-specific factors such as age, RA functional class, body mass index (BMI), prednisolone use, and chronic lung disease contributed more to the risk of hospitalized infection than specific biological agents. The incidence of pulmonary hospitalized infection was 50 and a crude IR of 4.0 per 100 PYs (95% CI, 3.1–5.3). After adjustment for confounders, adalimumab had a significantly higher HR for pulmonary hospitalized infection compared with tocilizumab: an adjusted HR (95% CI) was 4.43 (1.72–11.37) for adalimumab. BMI, prednisolone use, diabetes mellitus, and chronic lung disease were also significant factors associated with the risk of pulmonary hospitalized infection. Conclusions The magnitude of the risk of overall hospitalized infection was not determined by the type of biological agents, and patient-specific risk factors had more impact on the risk of hospitalized infection. For pulmonary hospitalized infections, the use of adalimumab was significantly associated with a greater risk of this complication than tocilizumab use.

Remission of chronic type ATL in a patient with rheumatoid arthritis after withdrawing methotrexate and infliximab combination therapy: a case report

Abstract A 70-year-old Japanese female was diagnosed with seropositive rheumatoid arthritis (RA) in January 2008. She had high disease activity and was treated with prednisolone, methotrexate (MTX) and infliximab (IFX). She was found to be positive for human T-lymphotropic virus type 1 (HTLV-1) antibody in 2012, and her HTLV-1 proviral DNA load (PVL) was as high as 5.82 copies per 100 white blood cells (WBCs). In 2014, she complained of fever and showed elevated soluble IL-2 receptors (sIL-2R) and WBCs. Abnormal lymphocytes with convoluted nuclei were found on blood smear analysis (13% of WBCs). She was negative for lymphadenopathy, skin lesion and organomegaly. She was diagnosed with chronic type adult T-cell leukaemia-lymphoma (ATL), and treatment with IFX and MTX was discontinued. Abnormal lymphocytes disappeared and sIL-2R level decreased a few months later. ATL did not relapse for more than 2 years. This case emphasises the need for careful observation in HTLV-1 positive patients with RA, especially in patients with high PVL. In addition, there is a possibility that prompt withdraw of biologics and MTX may contribute to the spontaneous remission of ATL.

Arteriosclerosis of Whole Aorta in Takayasu Arteritis

Persistent inflammation is a serious risk factor for arteriosclerosis and arteriosclerotic disease in Takayasu arteritis (TA)1,2. A female patient was diagnosed with TA at 32 years of age. She underwent treatment with glucocorticoids for about 1 year, and then the medication was discontinued. At 57 years of age, she presented to our hospital complaining of left back pain on …

The time-sequential changes of risk factors for adult T-cell leukemia development in human T-cell leukemia virus-positive patients with rheumatoid arthritis: a retrospective cohort study

Abstract Objective: This study aimed to investigate the time-sequential changes of risk factors for adult T-cell leukemia (ATL) development in human T-cell leukemia virus type 1 (HTLV-1)-positive rheumatoid arthritis (RA) patients. Methods: HTLV-1 infection was screened using particle agglutination assay and confirmed via western blotting in 365 RA patients. Twenty-three HTLV-1-positive RA patients were included in the study cohort. Blood samples were obtained from these patients at each observation time point. The values of HTLV-1 proviral load (PVL) and serum soluble IL-2 receptor (sIL2-R), which are risk factors for ATL development, were measured using real-time PCR and enzyme immunoassay, respectively. Results: The study cohort comprised 79 person-years. The median HTLV-1 PVL and sIL2-R values of the HTLV-1-positive RA patients were 0.44 copies per 100 white blood cells (WBCs) and 406 U/mL, respectively. Three HTLV-1-positive RA patients showed a high PVL value. No remarkable changes were observed in the PVL and sIL2-R values during the observation period. However, one elderly HTLV-1-positive RA patient who had a high PVL value developed ATL during treatment with methotrexate and infliximab. Conclusion: A thorough clinical assessment of the risk factors for ATL development may be necessary in daily clinical practice for RA patients in HTLV-1-endemic areas in Japan.

Leukocytapheresis in rheumatoid arthritis

In this article, we discussed leukocytapheresis (LCAP) for rheumatoid arthritis (RA). Recently, a simple and practical on-line continuous LACP system has been developed. It is equipped with a direct hemoperfusion column (Cellsorba®, Asahikasei Medical Co., Ltd.) packed with fine-diameter polyester fibers, which are commonly used to adsorb white blood cells to prevent a graft-versus-host reaction during blood transfusion. Clinical trials revealed that LCAP is a effective and safe therapy for patients with drug-resistant RA or RA complicated with vasculitis. Because the procedure is simple and requires no plasma substitutes and the volume needed for extracorporeal circulation is less than that for other plasmapheresis, LCAP might be accepted as an optional therapeutic modality for active RA that was refractory to conventional drug therapy including biological agents. The mechanism of the efficiency of LCAP on RA is unclear. LCAP may cause a reduction of activated T cells from affected joints, down-regulation of Pgp on helper T cells and restoration of Treg function, and that may modify the abnormal cytokine balance. These findings may explain some of the mechanisms by which the articular symptoms are improved by LCAP.

AB0124 Tocilizumab is Clinically Effective and Safe for Human T-Lymphotropic Virus Type 1 Positive Patients with Rheumatoid Arthritis Who Are Not Responsive to Anti-TNF Treatment

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 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

FRI0194 Treatment with anti-tumor necrosis factor (TNF) biologics to human t-lymphotropic virus type 1 (HTLV-1) positive patients with rheumatoid arthritis (RA): a case-control study

Objectives To see whether the clinical features and responses to anti-TNF of HTLV-1 positive patients with RA are different from those of HTLV-1 negative patients. Methods The clinical features and response to anti-TNF were compared between 10 female HTLV-1 positive RA patients and 20 age-matched female HTLV-1 negative patients, who were diagnosed based on the 1987 ACR criteria for RA. Therapeutics response was evaluated using the EULAR improvement criteria. Results Significantly higher baseline level of C-reactive protein (CRP) was observed in HTLV-1 positive patients than in HTLV-1 positive patients (P = 0.003). The value of disease activity score in 28 joints (DAS28) and the levels of erythrocyte sedimentation rate (ESR) tended to be higher in HTLV-1 positive patients. The discontinuation rate of anti-TNF was higher in HTLV-1 positive patients 6 months after the beginning of treatment than in HTLV-1 negative patients (30 % v.s 0 %, respectively). Most of reason for discontinuation was inefficacy of anti-TNF. EULAR response rate in 3 months of the treatment was worse in HTLV-1 positive patients than in HTLV-1 positive patients. The levels of CRP, ESR and the value of DAS28 remained to be significantly higher in carrier RA than non-carrier RA. There is no development of lymphoma or myelopathy during 2-years observation period in HTLV-1 positive patients. Conclusions The result of this small study suggested that HTLV-1 positive RA patients have high inflammation and resistance to the treatment with anti-TNF. Further study with larger number of cases is necessary to confirm these data. Disclosure of Interest None Declared