Efficacy and safety of abatacept or infliximab vs placebo in ATTEST: a phase III, multi-centre, randomised, double-blind, placebo-controlled study in patients with rheumatoid arthritis and an inadequate response to methotrexate.

OBJECTIVES: This double-blind trial evaluated the efficacy and safety of abatacept or infliximab vs placebo. The primary objective of this study was to evaluate the mean change from baseline in Disease Activity Score (based on erythrocyte sedimentation rates; DAS28 (ESR)) for the abatacept vs placebo groups at day 197. METHODS: Patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX) were randomised 3:3:2 to abatacept ( approximately 10 mg/kg every 4 weeks, n = 156), infliximab (3 mg/kg every 8 weeks, n = 165), or placebo (every 4 weeks, n = 110) and background MTX. Safety and efficacy were assessed throughout the study. RESULTS: Similar patient demographics and clinical characteristics were present at baseline between groups, with mean scores of approximately 1.7 for HAQ-DI and 6.8 for DAS28 (ESR). At 6 months, mean changes in DAS28 (ESR) were significantly greater for abatacept vs placebo (-2.53 vs -1.48, p<0.001) and infliximab vs placebo (-2.25 vs -1.48, p<0.001). For abatacept vs infliximab treatment at day 365, reductions in the DAS28 (ESR) were -2.88 vs -2.25. At day 365, the following response rates were observed for abatacept and infliximab, respectively: American College of Rheumatology (ACR) 20, 72.4 and 55.8%; ACR 50, 45.5 and 36.4%; ACR 70, 26.3 and 20.6%; low disease activity score (LDAS), 35.3 and 22.4%; DAS28-defined remission, 18.7 and 12.2%; good European League Against Rheumatism (EULAR) responses, 32.0 and 18.5%; and Health Assessment Questionnaire Disability Index (HAQ-DI), 57.7 and 52.7%. Mean changes in physical component summary (PCS) were 9.5 and 7.6, and mental component summary (MCS) were 6.0 and 4.0, for abatacept and infliximab, respectively. Over 1 year, adverse events (AEs) (89.1 vs 93.3%), serious AEs (SAEs) (9.6 vs 18.2%), serious infections (1.9 vs 8.5%) and discontinuations due to AEs (3.2 vs 7.3%) and SAEs (2.6 vs 3.6%) were lower with abatacept than infliximab. CONCLUSIONS: In this study, abatacept and infliximab (3 mg/kg every 8 weeks) demonstrated similar efficacy. Overall, abatacept had a relatively more acceptable safety and tolerability profile, with fewer SAEs, serious infections, acute infusional events and discontinuations due to AEs than the infliximab group. TRIAL REGISTRATION NUMBER: NCT00095147.

Listerial infections in patients with systemic lupus erythematosus.

Infection with Listeria monocytogenes is known to occur more frequently in immunosuppressed patients, including those receiving high-dose prednisone or cytotoxic therapy for collagen vascular disease. We reviewed three cases of listeriosis and systemic lupus erythematosus (SLE) seen at our institution, in addition to five cases reported in the English literature. Seven of the eight patients had non-CNS listerial infections. All patients but one had associated risk factors of either renal failure or pregnancy. From our review, we found that listeriosis is uncommon in SLE, and patients without renal failure or pregnancy do not seem to be at increased risk for listeriosis. Although most patients were treated with high-dose prednisone, with or without cytotoxic drugs, the role of immunosuppression by these drugs as a risk factor for listeriosis remained unclear.

Causes of diplopia.

A prospective study of 96 diplopia patients was analyzed concerning the common types and causes in order to develop early and proper management. Two-thirds (62) of the patients were male (64.6%). The average age was 34.5 +/- 15.7 years (+/- SD). The result revealed that the common types of diplopia were horizontal, vertical and torsional diplopia, respectively. The common causes of diplopia were head trauma (38.5%), systemic diseases from diabetes mellitus, hypertension (20.8%), undetermined group (15.6%), eye diseases (9.4%), and etc. Sixth cranial nerve paralysis was frequently found among the third, fourth and sixth cranial nerves. There were 13 cases of spontaneous fusion in the primary position. Only 7 of 12 surgical cases eventually achieved satisfactory alignment and fusion.

Clinical significance of low molecular weight IgM in patients with systemic lupus erythematosus.

The presence of low molecular weight (LMW) IgM was found in 45% of patients with systemic lupus erythematosus (SLE). Complete chart analysis of clinical and laboratory variables was done on 39 patients with negative LMW IgM (Group 1) and on 40 patients with positive LMW IgM (Group 2). There were statistically significant differences between the 2 groups related to age at onset, hemoglobin concentration, IgM levels, and levels of anti-dsDNA. There were 12 known deaths among the 40 patients in the positive group (30.0%) and only 4 known deaths among the 39 patients in the negative group (10.26%), p less than 0.1. There were no significant intergroup differences of race, sex, mucocutaneous manifestations, arthritis, positive ANA, positive serologic test for syphilis by rapid plasma reagent, Coombs' positive anemia, thrombocytopenia, serositis, incidence of renal and central nervous system involvement. Our study shows that LMW IgM occurred in about half of the patients with SLE. Patients with positive LMW IgM compared to those without it had greater mortality at an earlier age.

Spontaneous ureteral rupture in a patient with systemic lupus erythematosus.

A patient with known systemic lupus erythematosus had fever and symptoms of a lower urinary tract infection. Bone scintigraphy showed left ureteral perforation and necrosis with no demonstrable nephrolithiasis. It is speculated that this episode was due to lupus vasculitis.

Subciliary incision and skin-muscle eyelid flap for orbital fractures.

The lower eyelid skin-muscle flap is now widely used for cosmetic blepharoplasty, primarily because of the ease and speed of dissection it offers. We have used the same technique as a surgical approach in fractures of the orbital floor and rim. In a large clinical series seen over a three and a half-year period, no major complications were noted. This approach provides simple, extremely rapid exposure of the injured area and is an excellent alternative to other approaches to this site.

Muscle flaps and musculocutaneous flaps in the repair of urinary fistulas.

Techniques for including muscle flaps and musculocutaneous flaps in the repair of difficult vesicocutaneous, urethrocutaneous, and vesicovaginal fistulas are described. These methods have been uniformly successful in 10 consecutive patients. The incorporation of such healthy, well-vascularized tissue into the standard techniques of urologic repair can be a major factor in the successful management of these problems.

Interstitial lung disease in polymyositis and dermatomyositis.

An increased frequency of diffuse interstitial lung disease (DILD) was found in 7 of 15 cases of polymyositis and dermatomyositis seen in a 7-yr period. Affected patients had higher values of creatine phosphokinase and aldolase and more severe muscle necrosis than 8 patients with DILD. Early corticosteroid therapy sufficient to normalize enzymes apparently led to better resolutions of DILD. Active muscle necrosis seemed to be related to the development of DILD.

Spontaneous and X-ray induced chromosomal aberrations in selected connective tissue diseases.

Chromosome studies were performed on peripheral blood lymphocytes of 28 patients with connective tissue disease (6 with progressive systemic sclerosis, 6 with systemic lupus erythematosus, 6 with anti-nuclear antibody positive rheumatoid arthritis, 6 with anti-nuclear antibody negative rheumatoid arthritis, and 4 with mixed connective tissue disease) and on 17 controls to determine the frequency of spontaneous as well as X-ray (75 rads) induced aberrations. The mean spontaneous chromosomal aberration frequency for the 28 patients (9.1%) was significantly (P = 0.038) greater than that of controls (6.4%). When patients were categorized into specific clinically designated connective tissue disease subdivisions for comparison with the controls, only X-irradiated cells from the progressive systemic sclerosis group displayed significantly elevated levels of total chromosomal aberrations over those of the control group. The X-irradiated lymphocytes from these patients had an average of 23.6% aberrations per patient, while those of the control group showed an average of 14.9% per patient (P less than 0.05).