ObjectiveTo investigate whether antidrug antibodies and/or drug non‐trough levels predict the long‐term treatment response in a large cohort of patients with rheumatoid arthritis (RA) treated with adalimumab or etanercept and to identify factors influencing antidrug antibody and drug levels to optimize future treatment decisions.MethodsA total of 331 patients from an observational prospective cohort were selected (160 patients treated with adalimumab and 171 treated with etanercept). Antidrug antibody levels were measured by radioimmunoassay, and drug levels were measured by enzyme‐linked immunosorbent assay in 835 serial serum samples obtained 3, 6, and 12 months after initiation of therapy. The association between antidrug antibodies and drug non‐trough levels and the treatment response (change in the Disease Activity Score in 28 joints) was evaluated.ResultsAmong patients who completed 12 months of followup, antidrug antibodies were detected in 24.8% of those receiving adalimumab (31 of 125) and in none of those receiving etanercept. At 3 months, antidrug antibody formation and low adalimumab levels were significant predictors of no response according to the European League Against Rheumatism (EULAR) criteria at 12 months (area under the receiver operating characteristic curve 0.71 [95% confidence interval (95% CI) 0.57, 0.85]). Antidrug antibody–positive patients received lower median dosages of methotrexate compared with antidrug antibody–negative patients (15 mg/week versus 20 mg/week; P = 0.01) and had a longer disease duration (14.0 versus 7.7 years; P = 0.03). The adalimumab level was the best predictor of change in the DAS28 at 12 months, after adjustment for confounders (regression coefficient 0.060 [95% CI 0.015, 0.10], P = 0.009). Etanercept levels were associated with the EULAR response at 12 months (regression coefficient 0.088 [95% CI 0.019, 0.16], P = 0.012); however, this difference was not significant after adjustment. A body mass index of ≥30 kg/m2 and poor adherence were associated with lower drug levels.ConclusionPharmacologic testing in anti–tumor necrosis factor–treated patients is clinically useful even in the absence of trough levels. At 3 months, antidrug antibodies and low adalimumab levels are significant predictors of no response according to the EULAR criteria at 12 months.

Numerous studies report an increased frequency of minor physical anomalies (MPAs) in schizophrenic individuals compared with controls. However, these studies vary considerably regarding the magnitude of the case-control disparity and the topographical distribution of the anomalies. A meta-analysis was carried out on the existing MPA literature in an effort to better understand the relationship between MPAs and schizophrenia. Following a literature search, 13 studies were identified that met our inclusion criteria. Mean total MPA scores were available for 11 of these studies, whereas only seven studies provided regional MPA scores. For both the total MPA and regional MPA analyses, pooled effect sizes (Hedges' g and pooled odds ratios, respectively) were calculated along with tests of heterogeneity. For the total MPA analyses, a meta-regression approach was used to explore the relationship between possible moderator variables (e.g., number of MPA scale items) and effect size heterogeneity. The magnitude of the pooled effect size for the total MPA scores was high (1.131; p < 0.001), indicating significantly more overall MPAs in schizophrenic individuals. Significant effect size heterogeneity was present (p < 0.001); however, this heterogeneity could not be explained by any of the included moderator variables. The regional MPA analysis revealed significantly increased MPAs in all six anatomical regions (p < 0.05), although the pooled odds ratios for these regions did not differ significantly from one another. These results suggest a lack of regional specificity for MPAs in schizophrenia.

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The case histories are reported of two patients with systemic lupus erythematosus (SLE) who developed fatal neurological involvement, each presenting with cerebeliar and brainstem signs. Neuro-pathological changes were confined to the cerebellum and brainstem, with clear evidence of a small vessel vasculopathy. The predominant histological abnormalities were multiple perivascular haemorrhages in one case and classical vasculitic changes in the other.

Blau's syndrome refers to the rare familial presentation of a sarcoid-like granulomatous disease classically involving the skin, uveal tract and joints, in the absence of pulmonary manifestations. The onset is in childhood, and the mode of inheritance is thought to be autosomal dominant. We report a 15-year-old female and her 22-month-old daughter who presented with clinical features similar to those of Blau's syndrome. In addition to the skin, eye and joint disease, the mother also developed neurological involvement. In both patients long-term systemic corticosteroids were required to control the disease.