Hideki Kasahara

Maintenance treatment using abatacept with dose reduction after achievement of low disease activity in patients with rheumatoid arthritis (MATADOR) – A prospective, multicenter, single arm pilot clinical trial

Abstract Objectives: To preliminarily evaluate the feasibility of maintenance therapy with reduced dose of intravenous abatacept (ABT) to 250 mg/body/month after achieving remission or low disease activity (LDA). Patients and methods: RA patients treated with ABT at 13 sites were enrolled in this prospective interventional pilot study during the period between March 2013 and March 2015. Inclusion criteria were (1) age at 20 years or older, (2) under treatment with monthly intravenous ABT at approved doses, (3) DAS28-CRP lower than 2.7 at least for 6 months, (4) agreed to join this trial with written informed consent and (5) body weight under 125 kg. Enrolled patients were maintained with intravenous monthly ABT at a reduced dose of 250 mg/body (MATADOR protocol). The primary end point was the proportion of the patients continued with MATADOR protocol at week 48. MATADOR protocol was discontinued upon disease flare or other reasons such as patients’ request or severe adverse event (AE). Disease activities and structural changes were also evaluated. Results: Fifty-three patients fulfilled the entry criteria and were followed for 1-year. MATADOR protocol was continued for 1-year in 43 (81%) of the evaluated patients. Three patients experienced severe AEs. Mean DAS28-CRP and remission rate were 1.56 and 88% when ABT reduced and 1.80 and 81% at 1-year, respectively. Structural remission was achieved in 34 out of 42 evaluated patients. Conclusions: Reduced dose of intravenous ABT was proposed as a feasible choice for maintenance therapy for RA after achievement of remission/LDA, although further randomized trials would be awaited.

Tomosynthesis can facilitate accurate measurement of joint space width under the condition of the oblique incidence of X-rays in patients with rheumatoid arthritis

OBJECTIVE Accurate evaluation of joint space width (JSW) is important in the assessment of rheumatoid arthritis (RA). In clinical radiography of bilateral hands, the oblique incidence of X-rays is unavoidable, which may cause perceptional or measurement error of JSW. The objective of this study was to examine whether tomosynthesis, a recently developed modality, can facilitate a more accurate evaluation of JSW than radiography under the condition of oblique incidence of X-rays. METHODS We investigated quantitative errors derived from the oblique incidence of X-rays by imaging phantoms simulating various finger joint spaces using radiographs and tomosynthesis images. We then compared the qualitative results of the modified total Sharp score of a total of 320 joints from 20 patients with RA between these modalities. RESULTS A quantitative error was prominent when the location of the phantom was shifted along the JSW direction. Modified total Sharp scores of tomosynthesis images were significantly higher than those of radiography, that is to say JSW was regarded as narrower in tomosynthesis than in radiography when finger joints were located where the oblique incidence of X-rays is expected in the JSW direction. CONCLUSION Tomosynthesis can facilitate accurate evaluation of JSW in finger joints of patients with RA, even with oblique incidence of X-rays. ADVANCES IN KNOWLEDGE Accurate evaluation of JSW is necessary for the management of patients with RA. Through phantom and clinical studies, we demonstrate that tomosynthesis may achieve more accurate evaluation of JSW.

Crystalglobulinemia manifesting as chronic arthralgia and acute limb ischemia: A clinical case report

Rationale: Crystalglobulinemia is a rare disease caused by monoclonal immunoglobulins, characterized by irreversible crystallization on refrigeration. It causes systemic symptoms including purpura, arthralgia, and vessel occlusive conditions to be exacerbated by exposure to cold. We report a patient with crystalglobulinemia associated with monoclonal gammopathy of undetermined significance (MGUS) manifesting as chronic arthralgia and recurrent acute arterial occlusion. Presenting concerns: A 61-year-old man, who had been diagnosed with MGUS and who had arthralgia of unknown origin, presented with recurrent acute limb ischemia after surgical thromboembolectomy. Refrigeration of his serum formed precipitates that looked like needle-shaped crystals. These crystals did not dissolve with warming, which is not a characteristic of cryoglobulins. Skin biopsy results showed crystal-liked eosinophilic bodies in small vessels and we diagnosed crystalglobulinemia. Intervention and outcomes: Although he underwent above-knee amputation, he was treated with a bortezomib and dexamethasone-based chemotherapeutic regimen, following lenalidomide maintenance therapy. Finally, he achieved complete remission and serum crystalglobulins diminished. Lessons: Monoclonal gammopathy, previously diagnosed as MGUS, can cause systemic symptoms and thrombotic conditions by producing pathologic immunoglobulins, such as crystalglobulins. In such situations, MGUS, even when it has not progressed to multiple myeloma, can be a target of aggressive chemotherapy. Crystalglobulinemia should be considered for patients with monoclonal gammopathy manifesting as systemic and thrombotic symptoms exacerbated by cooling.

Hypertrophic osteoarthropathy: Detecting periosteal inflammation using Doppler ultrasound

A 69-year-old woman presented with a 2-month history of bilateral morning stiffness and arthralgia of the wrists, shoulders, and ankles in November 2016. She had undergone total hysterectomy and bilateral salpingo-oophorectomy for endometrial cancer 7 years ago and had subsequently undergone chemotherapy. However, her response to chemotherapy had been poor, and she had developed metastatic lung cancer 4 years later. A physical examination showed clubbed fingers and toes (Figure 1a, b), swelling of both ankles, and bilateral tenderness of the forearms and shins. Blood test results showed mildly elevated C-reactive protein and plasma vascular endothelial growth factor (VEGF) levels. The results were negative for rheumatoid factor, anticitrullinated protein antibody, and antinuclear antibody tests. A plain radiograph of the tibias showed periosteal thickening, and power Doppler ultrasound signals over the periosteum of the radius, ulna, and tibia indicated periosteal inflammation (Figure 2 a-d). Bone scintigraphy revealed the linear uptake of technetium-99m-labeled methylene diphosphonate in the radii, ulnas, and particularly, the tibias (Figure 3). Hypertrophic osteoarthropathy (HOA) associated with metastatic lung cancer was diagnosed. After treatment with a nonsteroidal anti-inflammatory drug and intravenous zoledronic acid, the pain in her joints and bones improved with reduction in Doppler signals. However, the metastatic lung tumors slowly enlarged, and the pain in her joints and bones progressively worsened.