Do selected drugs increase the risk of lupus? A matched case‐control study

WHAT IS ALREADY KNOWN ON THIS SUBJECT • Numerous previous case reports have suggested that lupus can be induced by a range of prescription medications. • Analytical studies quantifying risk of drug-induced lupus are lacking. WHAT THIS STUDY ADDS • This was the first large study to quantify risk of lupus associated with carbamazepine, hydralazine, and other prescription medicines suspected of inducing the disease. • We confirmed some, but not all, associations that have been hypothesized in case reports. • This study provides evidence that increased risks may be causal given the lack of an increased risk observed with deliberately selected ‘comparison’ drugs. AIM To investigate the association between risk of lupus and exposure to selected drugs implicated in risk of lupus in a number of case reports. METHODS In this matched nested case-control studywe utilized primary care data from the UK General Practice ResearchDatabase recorded between 1987 and 2001. Cases with at least one medical code for systemic lupus erythematosus or drug-induced lupus in their computerized records were matched to controls without a medical code for lupus or any other autoimmune disorder. Using conditional logistic regressionwe computed odds ratios (OR) and 95% confidence intervals (CI) for risk of lupus associated with exposure to selected drugs. RESULTS There were 875 incident cases, of which 12% (n= 107) had evidence of a prescription for one or more of the suspected drugs, and 3632 matched controls. For some drugs, prescriptions were too uncommon to be able to estimate associated risk of lupus. Despite small numbers of exposed patients and low statistical precision we observed an increased risk of lupus for hydralazine(OR = 6.62, 95% CI 1.03, 42.74), minocycline(OR = 4.23, 95% CI 2.65, 6.75) and carbamazepine(OR = 1.88, 95% CI 1.09, 3.22). There was some indication that the effect of carbamazepinewas restricted to women (P for interaction by gender = 0.047). CONCLUSION This study shows that even those drugs suggested by case reports as causing lupus cannot all be clearly shown to be associated, even in a very large population-based database. Our findings support causal relationships for carbamazepine, minocyclineand possibly hydralazine. Overall, drugs do not seem to be a major cause of lupus.