Objective
Immune checkpoint inhibitors (ICIs) for cancer therapy frequently induce immune‐related adverse effects (IRAEs). Therefore, most patients with preexisting autoimmune diseases have been excluded from clinical trials of ICIs. This study was undertaken to evaluate the safety and efficacy of ICIs in patients with preexisting autoimmune disease and cancer.
Methods
A retrospective cohort study was conducted from January 2017 to January 2018 via 3 French national networks of experts in oncology and autoimmunity. Adults with preexisting autoimmune disease who were receiving ICIs were assessed for the occurrence of flare of preexisting autoimmune disease, other IRAEs, and cancer response.
Results
The study included 112 patients who were followed up for a median of 8 months. The most frequent preexisting autoimmune diseases were psoriasis (n = 31), rheumatoid arthritis (n = 20), and inflammatory bowel disease (n = 14). Twenty‐four patients (22%) were receiving immunosuppressive therapy at ICI initiation. Autoimmune disease flare and/or other IRAE(s) occurred in 79 patients (71%), including flare of preexisting autoimmune disease in 53 patients (47%) and/or other IRAE(s) in 47 patients (42%), with a need for immunosuppressive therapy in 48 patients (43%) and permanent discontinuation of ICI in 24 patients (21%). The median progression‐free survival was shorter in patients receiving immunosuppressive therapy at ICI initiation (3.8 months versus 12 months; P = 0.006), confirmed by multivariable analysis. The median progression‐free survival was shorter in patients who experienced a flare of preexisting autoimmune disease or other IRAE, with a trend toward better survival in the subgroup without immunosuppressant use or ICI discontinuation.
Conclusion
Our findings indicate that flares or IRAEs occur frequently but are mostly manageable without ICI discontinuation in patients with a preexisting autoimmune disease. Immunosuppressive therapy at baseline is associated with poorer outcomes.
Objective. To determine the accuracy of salivary gland ultrasonography (SGUS) for diagnosing primary Sjögren's syndrome (SS) and to suggest modifications of the American-European Consensus Group (AECG) classification criteria.Methods. We conducted a cross-sectional study in a prospective cohort of patients with suspected primary SS that was established between 2006 and 2011. The echostructure of the bilateral parotid and submandibular glands was graded from 0 to 4, and the gland size was measured; blood flow to the parotid gland was assessed using Doppler waveform analysis. The reference standard was a clinical diagnosis of primary SS as determined by a group of experts blinded to the results of SGUS. Receiver operating characteristic (ROC) curve analysis was performed to compare the diagnostic value of the 0-4-point echostructure grade for each of the 4 major salivary glands, the sum of the grades for the 4 glands, and the highest grade among the 4 glands.Results. Of the 158 patients in the study, 78 had a diagnosis of primary SS according to the experts, including 61 patients (78.2%) who met the AECG criteria.Doppler waveform analysis and gland size measurement showed poor diagnostic performance. The results of ROC curve analysis showed that the highest grade among the 4 glands provided the best diagnostic value. The optimal grade cutoff was 2 (62.8% sensitivity and 95.0% specificity). A weighted score was constructed using scores for the 5 variables selected by logistic regression analysis, as follows: (salivary flow ؋ 1.5) ؉ (Schirmer's test ؋ 1.5) ؉ (salivary gland biopsy ؋ 3) ؉ (SSA/SSB ؋ 4.5) ؉ (SGUS ؋ 2). According to ROC curve analysis, a score of >5 of 12.5 had 85.7% sensitivity and 94.9% specificity, compared with 77.9% sensitivity and 98.7% specificity for the AECG criteria. The addition of SGUS to the AECG criteria increased sensitivity to 87.0% but did not change specificity.Conclusion. Modifications of the AECG criteria, including the addition of a SGUS score, notably improved diagnostic performance.
Despite a high dead-space volume (9-15 l), this new helmet interface is an efficient alternative to standard face mask during CPAP, even in cases of severe respiratory acidosis and hypercapnia. It allowed to provide long-duration CPAP, without any adverse events or clinical intolerance.
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