Differential effects of IL-6 blockade tocilizumab and TNF inhibitors on angiogenesis in synovial tissues from patients with rheumatoid arthritis.

OBJECTIVE: To compare the influences of tocilizumab (TCZ) and TNF inhibitors (TNFi) on the angiogenesis in synovial tissues of rheumatoid arthritis (RA). METHODS: Synovial tissues were obtained during joint operations from 13 RA patients treated with TCZ for at least 4 months with or without previous use of TNFi, from 13 RA patients with TNFi alone and from 10 RA patients with only conventional synthetic DMARDs (csDMARDs). Synovial tissues were evaluated by hematoxylin and eosin stain as well as by immunohistological staining with anti-CD31 in which the microvessel densities (MVD) were quantitated. Synovial histopathology was scored for various components. RESULTS: The most remarkable change in the synovium with TCZ was reduced angiogenesis as well as degeneration of lining layers irrespective of the previous use of TNFi. Thus, MVD in patients treated with TCZ with or without previous TNFi were significantly decreased compared with those in patients with TNFi alone or with csDMARDs. Moreover, MVD was significantly correlated with lining layer proliferation, but not with synovial stromal proliferation or inflammatory changes. CONCLUSIONS: These results demonstrated that inhibition of angiogenesis is a unique action of TCZ. Moreover, the data also suggest that lining layers proliferation might be closely associated with angiogenesis.

Spontaneously Resolved Recurrent Cervical Epidural Hematoma in a 37-Week Primigravida.

Study Design Case report. Objective To describe a patient with a recurrent spontaneous spinal epidural hematoma (SSEH) during pregnancy that had spontaneous remission. Methods A 27-year-old primigravida at 37 weeks' gestation suddenly felt a strong left shoulder pain without any trauma. She had a history of fenestration for a spontaneous cervical hematoma when she was 18 years old. An emergency magnetic resonance imaging revealed a recurrence of the cervical epidural hematoma at the C4-T1 level, but she had no paralysis. Results The patient subsequently underwent a cesarean section and delivered a healthy male infant. Her spinal epidural hematoma disappeared. Multislice computed tomography showed no evidence for a vascular malformation or tumor. Three years after the initial cesarean section, she underwent a second one and delivered another male infant. Conclusions We report on a rare case of recurrent SSEH during pregnancy with no neurologic deficits that was treated nonoperatively with close observation and resulted in spontaneous resolution. In such patients with no neurologic deficits, nonoperative management with close observation may be a reasonable alternative.

Long-term safety and efficacy of treatment with subcutaneous abatacept in Japanese patients with rheumatoid arthritis who are methotrexate inadequate responders.

OBJECTIVE: To assess the long-term safety, immunogenicity, and efficacy of subcutaneous (SC) abatacept in combination with methotrexate (MTX) in Japanese patients with rheumatoid arthritis who were MTX inadequate responders, in a long-term extension (LTE) to a double-dummy, double-blind study (NCT01001832). METHODS: Patients, who had previously received SC or intravenous (IV) abatacept with MTX (6-8 mg/week) for 24 weeks, received SC abatacept (125 mg/week) with MTX for an additional 52 weeks. Safety, immunogenicity, and efficacy were assessed. RESULTS: The LTE included 112 patients. SC abatacept was generally well tolerated in the LTE, with no new safety signals. American College of Rheumatology 20, 50, and 70 response rates, disease activity score 28 (C-reactive protein) remission rates (< 2.6), and Health Assessment Questionnaire-Disability Index response rates (≥ 0.3 improvement from baseline) achieved at the end of the double-blind period were maintained over the LTE and were comparable in patients who received SC or IV abatacept in the double-blind period. Seropositivity for immunogenicity occurred in 4 (3.6%) patients. Self-injection of SC abatacept was well controlled and not associated with additional safety events. CONCLUSIONS: SC abatacept had acceptable safety and was well tolerated and effective over the LTE (76 weeks in total), with low rates of immunogenicity in Japanese patients.

Efficacy, safety, pharmacokinetics and immunogenicity of abatacept administered subcutaneously or intravenously in Japanese patients with rheumatoid arthritis and inadequate response to methotrexate: a Phase II/III, randomized study.

OBJECTIVE: To evaluate efficacy and safety of subcutaneous (SC) and intravenous (IV) abatacept and background methotrexate (MTX) in Japanese patients with rheumatoid arthritis (RA) and inadequate response to MTX (MTX-IR). METHODS: Double-dummy, double-blind study (NCT01001832); 118 adults with ≥ 10 swollen joints, ≥ 12 tender joints and C-reactive protein (CRP) ≥ 0.8 mg/dL randomized 1:1 to SC abatacept (125 mg weekly) with IV loading (∼10 mg/kg on Day 1), or IV abatacept (∼10 mg/kg monthly) for 169 days, both also receiving MTX (6-8 mg/week). Primary endpoint was Day 169 American College of Rheumatology (ACR)20 response; other efficacy endpoints, safety and immunogenicity were assessed. RESULTS: Similar proportions of patients achieved ACR20 responses at Day 169 with SC (91.5% [95% CI 81.3, 97.2]) and IV abatacept (83.1% [71.0, 91.6]). ACR50/70 responses, adjusted mean changes from baseline in Health Assessment Questionnaire-Disability Index scores and remission rates (28-joint Disease Activity Score [CRP] < 2.6) were also comparable between groups. Serious adverse event frequencies (5.1% vs. 3.4%) were similar with both formulations. One patient per group tested seropositive for immunogenicity. Weekly SC abatacept dosing achieved mean serum concentrations > 10 µg/mL (minimum therapeutic target). CONCLUSIONS: SC abatacept demonstrated comparable efficacy and safety to IV abatacept, with low immunogenicity rates, in MTX-IR Japanese patients with RA.

A Fatal Case of Relapsing Pneumonia Caused by Legionella pneumophila in a Patient with Rheumatoid Arthritis After Two Injections of Adalimumab.

We present a rare fatal case of relapsing pneumonia caused by Legionella pneumophila in a patient with rheumatoid arthritis after only two injections of adalimumab. A 78-year-old Japanese woman with a 14-year history of rheumatoid arthritis was prescribed adalimumab because her disease activity remained high. However, 8 days after her second injection of adalimumab, she was admitted to our hospital and diagnosed with pneumonia caused by L. pneumophila. Following intravenous antibiotic therapy, she recovered completely from pneumonia and was discharged on day 10, but pneumonia relapsed, resulting in death 79 days after the first episode of pneumonia. L. pneumophila can lead to recurrence of pneumonia that can ultimately prove fatal, similar to the present case. A review of the pertinent literature is also presented.

Golimumab reduces disease activity of rheumatoid arthritis for 1 year and strongly inhibits radiographic progression in Japanese patients: partial but detailed results of the GO-FORTH and GO-MONO studies.

The objective of this study is to evaluate the efficacy of golimumab (GLM) in Japanese patients with active rheumatoid arthritis (RA) for 1 year. Nineteen patients were enrolled; 9 were randomized to the placebo (PBO) + methotrexate (MTX), GLM 50 mg + MTX, or GLM 100 mg + MTX therapy group; and 10 were randomized to the PBO, GLM 50 mg, or GLM 100 mg therapy group. One patient in the GLM 100 mg + MTX therapy group with median values from the GO-FORTH study was added. Data were evaluated by assessing the changes in DAS28-ESR, Health Assessment Questionnaire Disability Index (HAQ-DI), and total Sharp score (TSS) at week 52. Mean changes in DAS28-ESR in the MTX monotherapy, GLM 50 mg + MTX, GLM 100 mg + MTX, PBO, GLM 50 mg, and GLM 100 mg therapy groups were -2.70, -2.57, -2.27, -0.60, -2.53, and -2.53, respectively; the mean improvements in HAQ-DI were 0.188, 0.708, 0.377, 0.188, 1.042, and 0.625, respectively. The mean changes in TSS were 1.63, -0.33, -1.17, 4.25, 1.00, and 1.67, respectively. A significant difference was only observed in the mean TSS change between the PBO + MTX and the GLM 100 mg + MTX groups. However, in terms of mean changes in DAS28-ESR in the combination therapy groups, PBO + MTX therapy seemed to elicit similar results as the GLM 50 mg + MTX and GLM 100 mg + MTX therapies (no significant difference) because all four patients in the PBO + MTX therapy group may have received GLM from week 24 as a crossover. Combined GLM + MTX therapy reduced disease activity and strongly inhibited radiographic disease progression in patients with active RA at week 52.

Pneumococcal polyarticular septic arthritis after a single infusion of infliximab in a rheumatoid arthritis patient: a case report.

INTRODUCTION: We present a case of Streptococcus pneumoniae polyarticular septic arthritis in a patient with rheumatoid arthritis receiving a single infusion of infliximab. CASE PRESENTATION: A 38-year-old Japanese man with a 5-year history of seronegative rheumatoid arthritis had previously received sulphasalazine and methotrexate therapies and was on regular low-dose prednisolone therapy. Despite these treatments, his disease activity remained high and infliximab was introduced in addition to methotrexate, prednisolone, and folic acid. However, he was admitted to hospital with a fever of 40.6°C, chills, and polyarthralgia eight days after the first infusion of infliximab. His joints were swollen, painful, and warm. Laboratory data showed marked acute inflammation. He was diagnosed with bacterial septic polyarthritis, and emergency surgical joint lavage and drainage was performed at the knees along with needle aspiration and lavage of the ankles and right wrist. He was then given intravenous antibiotic therapy for 31 days. He made a good recovery and was discharged on day 37. CONCLUSIONS: We believe this is the first reported case of severe pneumococcal septic arthritis requiring hospitalization in a patient treated with infliximab. S. pneumonia is now a well-recognized but uncommon cause of polyarticular septic arthritis that can lead to cessation of therapy, as in our patient's case.

The migration of a broken luque rod: a case report.

An exceedingly rare complication of Luque segmental spinal instrumentation in spinal fractures is described. A patient was treated for fractures of the eighth and ninth thoracic vertebra associated with traumatic paraplegia using Luque segmental spinal instrumentation. Ten years postoperatively, broken rods and sublaminar wires were found. One of the broken rods migrated caudad penetrating the sacrum and protruding into the pelvic cavity. The rod had projected into the rectum, and was extracted through the wall of the rectum and the anus. This case report emphasizes the importance of careful surgical technique and long-term follow up for patients who had undergone spinal instrumentation surgery.

Intra-articular synovial lipoma of the knee joint (located in the lateral recess): a case report and review of the literature.

This report describes a rare intra-articular synovial lipoma of the knee joint which developed in a 66-year-old female. The patient suffered from sudden knee pain and a catching or slight interruption of normal motion of the left knee and then noticed the tumor. The tumor was located in the lateral recess of the knee joint and showed a signal intensity similar to subcutaneous fat on T1 and T2()-weighted magnetic resonance images. The arthroscopy revealed a smooth, globular, yellowish, encapsulated tumor extending into the lateral recess from the surface of the lateral condyle and the tumor was totally excised under arthroscopic guidance. Histologic examination of the specimen revealed a tumor composed of mature adipose cells covered by a thin fibrous layer of varying thickness and normal synovial lining cells. The diagnosis was intra-articular synovial lipoma. Intra-articular synovial lipomas should be distinguished from other similar lipomatoid conditions such as Hoffa disease and villous lipomatous proliferation of the synovial membrane (lipoma arborescens). Intra-articular synovial lipoma should be considered in the differential diagnoses when examining a patient with sudden knee pain, and a catching or locking knee.