Faculty Bibliography

Objective/UNASSIGNED:A common problem in clinical trials is missing data due to participant dropout and loss to follow-up, an issue which continues to receive considerable attention in the clinical research community. Our objective was to examine and compare current and alternative methods for handling missing data in SLE trials with a particular focus on multiple imputation, a flexible technique that has been applied in different disease settings but not to address missing data in the primary outcome of an SLE trial. Methods/UNASSIGNED:Data on 279 patients with SLE randomised to standard of care (SoC) and also receiving mycophenolate mofetil (MMF), azathioprine or methotrexate were obtained from the Lupus Foundation of America-Collective Data Analysis Initiative Database. Complete case analysis (CC), last observation carried forward (LOCF), non-responder imputation (NRI) and multiple imputation (MI) were applied to handle missing data in an analysis to assess differences in SLE Responder Index-5 (SRI-5) response rates at 52 weeks between patients on SoC treated with MMF versus other immunosuppressants (non-MMF). Results/UNASSIGNED:The rates of missing data were 32% in the MMF and 23% in the non-MMF groups. As expected, the NRI missing data approach yielded the lowest estimated response rates. The smallest and least significant estimates of differences between groups were observed with LOCF, and precision was lowest with the CC method. Estimated between-group differences were magnified with the MI approach, and imputing SRI-5 directly versus deriving SRI-5 after separately imputing its individual components yielded similar results. Conclusion/UNASSIGNED:The potential advantages of applying MI to address missing data in an SLE trial include reduced bias when estimating treatment effects, and measures of precision that properly reflect uncertainty in the imputations. However, results can vary depending on the imputation model used, and the underlying assumptions should be plausible. Sensitivity analysis should be conducted to demonstrate robustness of results, especially when missing data proportions are high.

Objective/UNASSIGNED:Epidemiological data for primary discoid lupus erythematosus (pDLE) remain limited, particularly for racial/ethnic populations in the USA. The Manhattan Lupus Surveillance Program (MLSP) is a population-based retrospective registry of cases with SLE and related diseases including pDLE in Manhattan and was used to provide estimates of the prevalence and incidence of pDLE across major racial/ethnic populations. Methods/UNASSIGNED:MLSP cases were identified from rheumatologists, hospitals and population databases. Two case definitions were used for pDLE: the primary case definition which was any physician diagnosis found in the chart and a secondary case definition which was limited to cases diagnosed by a rheumatologist and/or dermatologist. Rates among Manhattan residents were age-adjusted, and capture-recapture analyses were conducted to assess case under-ascertainment. Results/UNASSIGNED:Based on the primary definition, age-adjusted overall prevalence and incidence rates of pDLE among Manhattan residents were 6.5 and 0.8 per 100 000 person-years, which increased to 9.0 and 1.3 after capture-recapture adjustment. Prevalence and incidence rates were approximately two and six times higher, respectively, among women compared with men (p<0.0001). Higher prevalence was also found among non-Latino blacks (23.5) and Latinos (8.2) compared with non-Latino whites (1.8) and non-Latino Asians (0.6) (p<0.0001). Incidence was highest among non-Latino blacks (2.4) compared with all other racial/ethnic groups. Similar relationships were observed for the secondary case definition. Conclusion/UNASSIGNED:Data from the MLSP provide epidemiological estimates for pDLE among the major racial/ethnic populations in the USA and reveal disparities in pDLE prevalence and incidence by sex and race/ethnicity among Manhattan residents.

OBJECTIVE:Cutaneous neonatal lupus (cNL) occurs in possibly 5%-16% of anti-Ro±anti-La antibody-exposed infants. Data suggest in utero exposure to hydroxychloroquine (HCQ) may prevent cardiac NL. The aim was to assess whether in utero exposure to HCQ decreases the risk of cNL and/or delays onset. METHODS:A multicentre case-control study was performed with 122 cNL cases and 434 controls born to women with a rheumatological disease who had documentation of maternal anti-Ro±anti-La antibodies at pregnancy and confirmation of medication use and the child's outcome. A secondary analysis was performed on 262 cNL cases, irrespective of maternal diagnosis, to determine if HCQ delayed time to cNL onset. RESULTS:Twenty (16%) cNL cases were exposed to HCQ compared with 146 (34%) controls (OR 0.4 (95% CI 0.2 to 0.6); p<0.01). Exposure to HCQ was associated with a reduced risk of cNL; exposure to anti-La antibody and female gender were associated with an increased risk of cNL. Exposure to HCQ remained significantly associated with a reduced cNL risk in the analyses limited to mothers with systemic lupus erythematosus and those who developed rash ≤1 month. When analysing all 262 cNL cases, HCQ-exposed infants were older (6.0 (95% CI 5.7 to 6.3) weeks) at cNL onset versus HCQ-non-exposed infants (4.4 (95% CI 3.9 to 5.0) weeks), but the difference was not statistically significant (p=0.21). CONCLUSION/CONCLUSIONS:Exposure to HCQ was associated with a reduced risk of cNL. Among cNL cases, those exposed to HCQ tend to have later onset of rash. Both findings suggest a protective effect of HCQ on cNL.

Non-bacterial thrombotic endocarditis in antiphospholipid syndrome presents a management dilemma. Large mobile valvular lesions pose an increased risk of stroke and arterial embolization. However, surgical excision or valve replacement in such patients carries high morbidity and mortality, while anticoagulation alone has limited data. We describe two patients with antiphospholipid syndrome presenting with neurologic events and large non-bacterial aortic valve vegetations. Both patients were successfully managed with anticoagulation and demonstrated rapid dissolution of lesions without evidence of recurrent embolic events. We provide a literature review describing additional cases managed with anticoagulation with dissolution of valvular lesions over time. Our cases further support the efficacy and safety of anticoagulation in patients with antiphospholipid syndrome and non-bacterial thrombotic endocarditis in the context of arterial embolization.