Anti-citrullinated protein antibody profiles predict changes in disease activity in patients with rheumatoid arthritis initiating biologics.

OBJECTIVES: To determine whether an expanded antigen-specific ACPA profile predicts changes in disease activity in patients with RA initiating biologics. METHODS: The study included participants from a prospective, non-randomized, observational RA cohort. For this sub-study, treatment groups of interest included biologic-naïve initiating anti-TNF, biologic-exposed initiating non-TNF, and biologic-naïve initiating abatacept. ACPAs to 25 citrullinated peptides were measured using banked enrolment serum. Principal component analysis (PCA) was performed and associations of resulting principal component (PC) scores (in quartiles) and anti-CCP3 antibody (≤15, 16-250 or >250 U/ml) with EULAR (good/moderate/none) treatment response at 6 months were examined using adjusted ordinal regression models. RESULTS: Participants (n = 1092) had a mean age of 57 (13) years and 79% were women. At 6 months, 68.5% achieved a moderate/good EULAR response. There were three PCs that cumulatively explained 70% of variation in ACPA values. In models including the three components and anti-CCP3 antibody category, only PC1 and PC2 were associated with treatment response. The highest quartile for PC1 (odds ratio [OR] 1.76; 95% CI: 1.22, 2.53) and for PC2 (OR 1.74; 95% CI: 1.23, 2.46) were associated with treatment response after multivariable adjustment. There was no evidence of interaction between PCs and treatment group in EULAR responses (P-value for interaction >0.1). CONCLUSION: An expanded ACPA profile appears to be more strongly associated with biologic treatment response in RA than commercially available anti-CCP3 antibody levels. However, further enhancements to PCA will be needed to effectively prioritize between different biologics available for the treatment of RA.

Toxicology Test Results for Public Health Surveillance of the Opioid Epidemic: Retrospective Analysis.

Background: Addressing the opioid epidemic requires timely insights into population-level factors, such as trends in prevalence of legal and illegal substances, overdoses, and deaths. Objective: This study aimed to examine whether toxicology test results of living individuals from a variety of sources could be useful in surveilling the opioid epidemic. Methods: A retrospective analysis standardized, merged, and linked toxicology results from 24 laboratories in Marion County, Indiana, United States, from September 1, 2018, to August 31, 2019. The data set consisted of 33,787 Marion County residents and their 746,681 results. We related the data to general Marion County demographics and compared alerts generated by toxicology results to opioid overdose-related emergency department visits. Nineteen domain experts helped prototype analytical visualizations. Main outcome measures included test positivity in the county and by ZIP code; selected demographics of individuals with toxicology results; and correlation of toxicology results with opioid overdose-related emergency department visits. Results: Four percent of Marion County residents had at least 1 toxicology result. Test positivity rates ranged from 3% to 19% across ZIP codes. Males were underrepresented in the data set. Age distribution resembled that of Marion County. Alerts for opioid toxicology results were not correlated with opioid overdose-related emergency department visits. Conclusions: Analyzing toxicology results at scale was impeded by varying data formats, completeness, and representativeness; changes in data feeds; and patient matching difficulties. In this study, toxicology results did not predict spikes in opioid overdoses. Larger, more rigorous and well-controlled studies are needed to assess the utility of toxicology tests in predicting opioid overdose spikes.