Certain drugs, antinuclear antibodies linked to GI dysfunction in SSc

A phenome-wide association study (pheWAS) has found known and potentially new risk factors for gastrointestinal (GI) dysfunction in systemic sclerosis (SSc), which include drug classes such as opioid, antimuscarinic, and endothelin receptor antagonist, and antinuclear antibodies (ANAs) subgroup.

Overall, 12,535 documented clinical assessments of 2,058 consenting SSc patients at the Royal Free Hospital in the UK were included in the detailed phenotyping. The authors mapped diagnoses and drugs to structured dictionaries of terms (Disease Ontology project and DrugBank Open Data, respectively).

A pheWAS model was used to examine the association between six important SSc-GI domains (ie, constipation, diarrhoea, dysmotility, incontinence, gastroesophageal reflux, and small intestinal bacterial overgrowth [SIBO]) and exposure to different comorbidities and drugs.

The authors then confirmed and explored “hits” from the pheWAS model in a subgroup reporting quantitative GI symptom scores from the University of California Los Angeles Scleroderma Clinical Trials Consortium Gastrointestinal Tract Instrument 2.0 (GIT 2.0) questionnaire.

In total, 1,564 individuals were enrolled in the pheWAS analysis. Using the dataset, the authors were able to identify 673 distinct diagnoses and 634 distinct drugs, as well as SSc-specific phenotypes such as ANAs. In the pheWAS analysis, drugs, diagnoses, and ANAs were found to be associated with six important SSc-GI outcomes, namely diarrhoea, dysmotility, reflux, constipation, incontinence, and SIBO.

“Subsequently, using GIT 2.0 symptom scores links with SSc-GI were confirmed for 22 drugs, four diagnoses, and three ANAs,” the authors said.