Development and performance of the Clinical Trials ESSDAI (ClinTrialsESSDAI), consisting of frequently active clinical domains, in two randomised controlled trials in primary Sjogren's syndrome

Objective. To develop and evaluate the Clinical Trials EULAR Sjogren's Syndrome Disease Activity Index (ClinTrialsESSDAI), consisting of frequently active clinical domains of the ESSDAI, using two randomised controlled trials in primary Sjogren's syndrome (pSS). Methods. The ASAP-III trial in abatacept (80 pSS patients) and TRACTISS trial in rituximab (133 pSS patients) were analysed. The most frequently active clinical domains were selected, and ClinTrialsESSDAI total score was calculated using existing weightings of the ClinESSDAI (which also excludes the biological domain). Performance of the ClinTrialsESSDAI was compared to ClinESSDAI and ESSDAI. Responsiveness was assessed using standardised response mean (SRM), and discrimination was assessed using adjusted mean difference. Results. Besides the biological domain, the most frequently active domains were glandular, articular, haematological, constitutional, lymphadenopathy and cutaneous. These domains were selected for the ClinTrialsESSDAI. At primary endpoint visits, SRM values of ClinTrialsESSDAI, ClinESSDAI and ESSDAI were respectively -0.65/-0.59, -0.63/-0.59 and - 0.64/-0.61 for abatacept/placebo and -0.33/-0.13, -0.34/0.12 and -0.41/-0.16 for rituximab/placebo. Adjusted mean differences between active treatment and placebo groups were respectively -1.7, -1.4 and -1.1 for ASAP-III and -1.1, -1.1 and -1.2 for TRACTISS. Conclusion. The ClinTrialsESSDAI, consisting of six frequently active clinical domains of the ESSDAI, shows closely similar responsiveness and discrimination between treatment groups compared to the ClinESSDAI and ESSDAI. Therefore, this ClinTrialsESSDAI is not preferable to ClinESSDAI and ESSDAI for use as primary endpoint. A composite endpoint combining response at multiple clinically relevant items seems more suitable as primary study endpoint in pSS

Checkpoint inhibition-induced sicca:a type II interferonopathy?

The advent of immune checkpoint inhibitor (ICI) therapy for treatment of cancers is unfortunately coupled with a broad panoply of side effects, related to non-specific activation of the immune system. One such side effect is the development of sicca complaints. This culminates in a proportion of patients who, according to the ACR-EULAR 2016 criteria, can be classified as suffering from the autoimmune disease primary Sjögren's syndrome (pSS). Although salivary gland (SG) loss of function is often seen after ICI therapy, the similarities with 'classical' pSS patients would appear to end there. Despite the presence of focal lymphocytic sialadenitis typical for SS in salivary gland biopsies from patients receiving ICI therapy, the nature of the immune infiltration (foci) following ICI use (T-cell dominated) is starkly different to that in pSS (B-cell dominated). The SG parenchyma post-ICI use does not present with germinal centres, lymphoepithelial lesions or IgG plasma cells, which are frequently found in the SG in pSS. Here we review the functional deterioration of SGs following ICI use, the SG parenchyma phenotype associated with this, and ultrasound abnormalities. We conclude by suggesting that ICI-induced SG dysfunction may represent a new interferonopathy, driven by IFNγ, and that this 'pSS' patient cohort may require a different management than classical pSS patients

Checkpoint inhibition-induced sicca:a type II interferonopathy?

The advent of immune checkpoint inhibitor (ICI) therapy for treatment of cancers is unfortunately coupled with a broad panoply of side effects, related to non-specific activation of the immune system. One such side effect is the development of sicca complaints. This culminates in a proportion of patients who, according to the ACR-EULAR 2016 criteria, can be classified as suffering from the autoimmune disease primary Sjögren's syndrome (pSS). Although salivary gland (SG) loss of function is often seen after ICI therapy, the similarities with 'classical' pSS patients would appear to end there. Despite the presence of focal lymphocytic sialadenitis typical for SS in salivary gland biopsies from patients receiving ICI therapy, the nature of the immune infiltration (foci) following ICI use (T-cell dominated) is starkly different to that in pSS (B-cell dominated). The SG parenchyma post-ICI use does not present with germinal centres, lymphoepithelial lesions or IgG plasma cells, which are frequently found in the SG in pSS. Here we review the functional deterioration of SGs following ICI use, the SG parenchyma phenotype associated with this, and ultrasound abnormalities. We conclude by suggesting that ICI-induced SG dysfunction may represent a new interferonopathy, driven by IFNγ, and that this 'pSS' patient cohort may require a different management than classical pSS patients

Nitrogen cycling rates and light effects in tropical Lake Maracaibo, Venezuela

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109860/1/lno19984381814.pd