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Objective:To report adverse events (AEs) seen in a large cohort of patients with juvenile idiopathic arthritis (JIA) treated with tumour necrosis factor (TNF)α blockers (infliximab and etanercept).Methods:All patients with JIA treated with infliximab or etanercept at the Paediatric Rheumatologic Centre of the G Pini Institute (Milan, Italy) from November 1999 to February 2006, were enrolled in an open, single-centre, long-term prospective studyResults:In all, 163 patients (68 infliximab, 95 etanercept) were enrolled. Mean (SD) age of onset was 6.4 (4.8) years, mean age 17.1 (9.2) years, mean therapy duration 22.9 (17.6) months. A total of 45 patients (32 infliximab, 13 etanercept) failed to respond to or did not tolerate the first therapy and switched to a second one. In all, 208 treatments (81 infliximab, 127 etanercept) were performed. A total of 71 AEs occurred in 51 (62.9%) patients on infliximab and led to discontinuation in 26 (32.1%); 133 AEs occurred in 69 (54.3%) patients on etanercept and led to discontinuation in 18 (14.2%). Some AEs, such as thrombocytopoenia, neuropsychiatric disorders, new onset of Crohn disease and new onset or flare-up of chronic iridocyclitis (CIC), are unusual and have rarely been described before, yet proved to be significant in frequency and/or clinically noteworthy in the large population we followed.Conclusions:In our 6-year study, anti-TNFα agents infliximab and etanercept were well tolerated and safe, and were associated with only few serious, but all reversible, AEs. However, such inhibitors are associated with various and numerous AEs. Children and young adults affected by JIA should be carefully monitored so as to limit the risk of AEs during anti-TNFα therapy as much as possible.

We report the spectrum of ocular toxicity following accidental inoculation of latex of Calotropis procera (Sodom apple) in 29 eyes between January 2003 and December 2006. All patients presented with sudden painless dimness of vision with photophobia. Twenty-five (86%) patients had initial visual acuity of less than 20/60. All eyes had conjunctival congestion and mild to severe corneal edema with Descemet's folds. Three (10%) eyes had an epithelial defect, nine (31%) had iridocyclitis, and seven (24%) had associated secondary glaucoma. After treatment with topical corticosteroids, antiglaucoma agents, cycloplegics, hypertonic saline and tears supplements, 27 (93%) eyes recovered completely within 3-14 days. After three months, 17 (74%) out of 23 eyes showed a significant low endothelial cell count compared to the normal fellow eye ( P 0.001). The latex of Calotropis procera causes significant ocular morbidity which may be preventable by simple health education. The long-term effect on corneal endothelium has to be studied further.

Malignant pleural mesothelioma is a highly aggressive cancer with poor prognosis and few treatment options following progression on platinum-containing chemotherapy. We assessed the safety and efficacy of pembrolizumab (an anti-programmed cell death receptor 1 [PD-1] antibody) in advanced solid tumours expressing programmed cell death ligand 1 (PD-L1) and report here on the interim analysis of the malignant pleural mesothelioma cohort. Previously treated patients with PD-L1-positive malignant pleural mesothelioma were enrolled from 13 centres in six countries. Patients received pembrolizumab (10 mg/kg every 2 weeks) for up to 2 years or until confirmed progression or unacceptable toxicity. Key eligibility criteria included measurable disease, failure of standard therapy, and Eastern Cooperative Oncology Group performance status of 0 or 1. PD-L1 positivity was defined as expression in 1% or more of tumour cells by immunohistochemistry. Response was assessed based on investigator review using the Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1). Primary endpoints were safety and tolerability, analysed in the all-patients-as-treated population, and objective response, analysed for the full-analysis set. This trial is registered with ClinicalTrials.gov, number NCT02054806, and is ongoing but not recruiting participants. As of June 20, 2016, 25 patients received pembrolizumab. 16 (64%) patients reported a treatment-related adverse event; the most common adverse event were fatigue (six [24%]), nausea (six [24%]), and arthralgia (five [20%]). Five (20%) patients reported grade 3 treatment-related adverse events. Three (12%) patients required dose interruption because of immune-related adverse events: one (4%) of 25 each had grade 3 rhabdomyolysis and grade 2 hypothyroidism; grade 3 iridocyclitis, grade 1 erythema multiforme, and grade 3 erythema; and grade 2 infusion-related reaction. No treatment-related deaths or discontinuations occurred. Five (20%) patients had a partial response, for an objective response of 20% (95% CI 6·8–40·7), and 13 (52%) of 25 had stable disease. Responses were durable (median response duration 12·0 months [95% CI 3·7 to not reached]); two patients remained on treatment at data cutoff. Pembrolizumab appears to be well tolerated and might confer anti-tumour activity in patients with PD-L1-positive malignant pleural mesothelioma. Response durability and efficacy in this patient population warrants further investigation. Merck.