Risk-stratified monitoring for sulfasalazine toxicity: prognostic model development and validation

Abhishek, A.; Grainge, Matthew J.; Card, Tim; Williams, Hywel C.; Taal, Maarten W.; Aithal, Guruprasad P.; Fox, Christopher P.; Mallen, Christian D.; Stevenson, Matthew D.; Nakafero, Georgina; Riley, Richard D.

Abstract

Background Sulfasalazine induced cytopenia, nephrotoxicity, and hepatotoxicity is uncommon during long-term treatment. Some guidelines recommend three monthly monitoring blood-tests indefinitely while others recommend stopping monitoring after one year. To rationalise monitoring we developed and validated a prognostic model for clinically significant blood, liver, or kidney toxicity during established sulfasalazine treatment.

Design Retrospective cohort study.

Setting UK primary-care. Data from Clinical Practice Research Datalink Gold and Aurum formed independent development and validation cohorts.

Participants Age ≥18 years, new diagnosis of an inflammatory condition and sulfasalazine prescription.

Study period 01/01/2007 to 31/12/2019.

Outcome Sulfasalazine discontinuation with abnormal monitoring blood-test result. Analysis: Patients were followed-up from six months after first primary-care prescription to the earliest of outcome, drug discontinuation, death, 5 years, or 31/12/2019.Penalised Cox regression was performed to develop the risk equation. Multiple imputation handled missing predictor data. Model performance was assessed in terms of calibration and discrimination.

Results 8,936 participants were included in the development cohort (473 events, 23,299 person-years) and 5,203 participants were included in the validation cohort (280 events, 12,867 person-years).Nine candidate predictors were included. The optimism adjusted R2D and Royston D statistic in the development data were 0.13 and 0.79 respectively. The calibration slope (95% confidence interval (CI)) and Royston D statistic (95% CI) in validation cohort was 1.19 (0.96-1.43) and 0.87 (0.67-1.07) respectively.

Conclusion This prognostic model for sulfasalazine toxicity utilises readily available data and should be used to risk-stratify blood-test monitoring during established sulfasalazine treatment.<colcnt=1>

Citation

Abhishek, A., Grainge, M. J., Card, T., Williams, H. C., Taal, M. W., Aithal, G. P., Fox, C. P., Mallen, C. D., Stevenson, M. D., Nakafero, G., & Riley, R. D. Risk-stratified monitoring for sulfasalazine toxicity: prognostic model development and validation

• Working Paper Type: Working Paper
• Deposit Date: Mar 18, 2024
• Publicly Available Date: Mar 19, 2024
• DOI: https://doi.org/10.1101/2023.12.15.23299947
• Public URL: https://nottingham-repository.worktribe.com/output/28716245
• Publisher URL: https://www.medrxiv.org/content/10.1101/2023.12.15.23299947v1