Investigation of treatment continuity, usefulness, and nocebo effect in switching from the original etanercept to its biosimilar in patients with rheumatoid arthritis: A JET observational study in Japanese clinical practice.

OBJECTIVES: To assess the usefulness and onset of nocebo effects after switching from the original etanercept (ETN) to a biosimilar (BS) in routine clinical practice at rheumatology clinics in Japan (13 sites). METHODS: A total of 165 patients (87.0% women, age = 57.88 ± 15.07 years, and disease duration = 10.32 ± 7.71 years), whose low disease activity was maintained with the original ETN for ≥12 weeks, and who agreed to switch treatment to its BS, were included. The end-points were disease activity score 28 (DAS28)-C-reactive protein and DAS28-erythrocyte sedimentation rate. RESULTS: No significant difference was observed between the changes in DAS28-C-reactive protein and DAS28-erythrocyte sedimentation rate >12 weeks before switching and >12 weeks after switching (P = 0.132 and 0.334, respectively). The treatment continuation rate during the 52 weeks after switching to BS was 97.3%. During this period, BS was discontinued in only four patients, and no nocebo effects were suspected in these four patients. CONCLUSION: Switching from ETN to BS was effective even in routine clinical practice at rheumatology clinics in Japan, and no nocebo effects were observed. Sufficient explanations to patients by rheumatologists and the additional payment for drug costs between patients at hospital visits effectively improved the continuation rate without any nocebo effect.

Associations between proinflammatory cytokines in the synovial fluid and radiographic grading and pain-related scores in 47 consecutive patients with osteoarthritis of the knee.

BACKGROUND: One of the sources of knee pain in osteoarthritis (OA) is believed to be related to local chronic inflammation of the knee joints, which involves the production of inflammatory cytokines such as tumor necrosis factor alpha (TNFα), interleukin (IL)-6, and nerve growth factor (NGF) in the synovial membrane, and these cytokines are believed to promote pathological OA. In the present study, correlations between proinflammatory cytokines in knee synovial fluid and radiographic changes and functional scores and pain scores among OA patients were examined. METHODS: Synovial fluid was harvested from the knees of 47 consecutive OA patients, and the levels of TNFα, IL-6, and NGF were measured using enzyme-linked immunosorbent assays. Osteoarthritic knees were classified using Kellgren-Lawrence (KL) grading (1-4). The Western Ontario and McMaster University Osteoarthritis Index (WOMAC) was used to assess self-reported physical function, pain, and stiffness. RESULTS: TNFα and IL-6 were detectable in knee synovial, whereas NGF was not. TNFα was not correlated with the KL grade, whereas IL-6 had a significantly negative correlation. We observed differences in the correlations between TNFα and IL-6 with WOMAC scores and their subscales (pain, stiffness, and physical function). TNFα exhibited a significant correlation with the total score and its 3 subscales, whereas IL-6 exhibited a moderately significant negative correlation only with the subscale of stiffness. CONCLUSIONS: The present study demonstrated that the concentrations of proinflammatory cytokines are correlated with KL grades and WOMAC scores in patients with knee OA. Although TNFα did not have a significant correlation with the radiographic grading, it was significantly associated with the WOMAC score. IL-6 had a significant negative correlation with the KL grading, whereas it had only a weakly significant correlation with the subscore of stiffness. The results suggest that these cytokines play a role in the pathogenesis of synovitis in osteoarthritic knees in different ways: TNFα is correlated with pain, whereas IL-6 is correlated with joint function.

Correlation Between Walking Ability and Monthly Care Costs in Elderly Patients After Surgical Treatments for Hip Fractures.

OBJECTIVE: To validate the relationship between residual walking ability and monthly care cost as well as long-term care insurance (LTCI) certification level in elderly patients after surgical treatment for hip fractures in Japan. METHODS: Elderly patients aged >75 years who underwent surgical treatment for hip fractures in our hospital were included. The preand post-surgical (6-month) walking ability and LTCI certification and the presence or absence of dementia was determined from medical records and questionnaires. Walking ability was classified into 6 levels used in our daily medical practice. Based on these data, we correlated the relationship between walking ability and the LTCI certification level. Further, based on the official statistics pertaining to the average monthly costs per person at each LTCI certification level, we evaluated the relationship between walking ability and monthly care cost. RESULTS: A total of 105 cases (mean age, 80.2 years; 16 men; 39 patients with dementia) were included. The correlation between walking ability and average monthly cost per person as well as LTCI certification level at 6 months postoperatively (r=0.58) was demonstrated. The correlation was found in both groups with and without dementia. CONCLUSION: The ability to walk reduced the cost of care in elderly patients who experienced hip fracture, regardless of the presence of dementia.

Sudden glottic stenosis caused by cricoarytenoid joint involvement due to rheumatoid arthritis.

A woman with rheumatoid arthritis (RA) experienced glottic stenosis approximately two months after switching from etanercept to tocilizumab. Cricoarytenoid joint (CAJ) arthritis due to RA was diagnosed. An awake tracheostomy saved the relievable airway, and the administration of methylprednisolone and infliximab ameliorated the flare-up and glottic stenosis. A follow-up examination revealed the recovery of the patient's normal voice and good control of RA with infliximab and methotrexate. Although general physicians do not frequently encounter patients with symptomatic CAJ arthritis, this condition should be considered as it can be life-threatening. Therefore, when detected, it should be diagnosed and treated immediately.

Gynecomastia associated with low-dose methotrexate therapy for rheumatoid arthritis.

A 68-year-old man with a 3-year history of rheumatoid arthritis (RA) developed gynecomastia 3 months after beginning oral low-dose methotrexate (MTX) therapy. Four months after MTX therapy was discontinued, the gynecomastia symptoms improved. Only eight cases of gynecomastia resulting from low-dose MTX administration have been reported worldwide, and no cases have previously been reported in Japan. Although it occurs infrequently, gynecomastia resulting from low-dose MTX therapy should be considered in male patients with RA.

Correlation between severity of rheumatoid arthritis and manner and extent of cervical lesion.

Abstract To determine the proper management of treatment for rheumatoid cervical lesions, we investigated the clinical course of the cervical spine in rheumatoid arthritis (RA). The severity of RA was classified into three groups according to the disease subsets advocated by Ochi et al.: the less erosive subset (LES), the more erosive subset (MES), and mutilating disease (MUD). Then the following radiographic assessments were performed on cervical roentogenograms: atlantoaxial subluxation (AAS), vertical subluxation (VS), and subaxial subluxation (SAS). One hundred and seventy-four patients were available for this study. The mean age of the patients was 60.9 years (19-85 years). The average duration from the onset of RA was 19.1 years (10-40 years). Eighty-seven patients were classified as LES, 69 were MES, and 18 were MUD. We found that few patients in the LES group had required an operation on the cervical spine. AAS was seen in about 60% of the MES patients, but few cases had VS or SAS, and most operations were atlantoaxial fusion. All patients in the MUD group had some cervical instabilities. Not only VS but also SAS were seen in more than half of these patients, and many patients had required occipitothoracic fusion.