Association Between Statin Use and Lupus-Like Syndrome Using Spontaneous Reports

Jong, Hilda J. I. de; Tervaert, Jan Willem Cohen; Saldi, Siti Rizny F; Vandebriel, Rob J.; Souverein, Patrick C.; Meyboom, R.H.B.; Loveren, Henk Van; Klungel, Olaf H.

doi:10.1016/j.semarthrit.2011.06.002

Cited by 29 publications

(17 citation statements)

References 39 publications

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“…In a previous study conducted by our research group, it was found that statin use was more often reported in patients with lupus-like syndrome than in patients who experienced other adverse drug events 10. The findings of this study were consistent with the results of a study that used the French PharmacoVigilance database 13.…”

Section: Discussionsupporting

confidence: 89%

Pattern of risks of systemic lupus erythematosus among statin users: a population-based cohort study

et al. 2017

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Section: Discussionsupporting

confidence: 89%

Pattern of risks of systemic lupus erythematosus among statin users: a population-based cohort study

et al. 2017

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“…In line with this hypothesis, we have recently shown in an observational study that statin use was associated with an increased risk of developing rheumatoid arthritis (RA) [9]. Moreover, based on individual case reports we found a positive association between statin use and the occurrence of lupus-like syndrome [10]. This latter association was recently confirmed by another research group [11].…”

Section: Introductionmentioning

confidence: 52%

Statins accelerate the onset of collagen type II-induced arthritis in mice

et al. 2012

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IntroductionStatins (hydroxymethylglutaryl coenzyme A reductase inhibitors) are effective in reducing the risk of cardiovascular morbidity and mortality in patients with hyperlipidemia, hypertension, or type II diabetes. Next to their cholesterol-lowering activity, statins have immunomodulatory properties. Based on these properties, we hypothesized that statin use may eventually lead to dysregulation of immune responses, possibly resulting in autoimmunity. We have recently shown in an observational study that statin use was associated with an increased risk of developing rheumatoid arthritis. Our objective was to investigate whether a causal relationship could be established for this finding.MethodsThe mouse collagen type II (CII)-induced arthritis (CIA) model was used, with immunization, challenge, and euthanasia at days 0, 21, and 42, respectively. Statins were given orally before (day -28 until day 21) or after (day 21 until day 42) CIA induction. Atorvastatin (0.2 mg/day) or pravastatin (0.8 mg/day) was administered. Arthritis was recorded three times a week. Serum anti-CII autoantibodies and cytokines in supernatants from Concanavalin-A-stimulated lymph node cells and CII-stimulated spleen cells were measured.ResultsStatin administration accelerated arthritis onset and resulted in 100% arthritic animals, whereas only seven out of 12 nonstatin control animals developed arthritis. Atorvastatin administration after CIA induction resulted in earlier onset than atorvastatin administration before induction, or than pravastatin administration before or after induction. The arthritic score of animals given pravastatin before CIA induction was similar to that of the nonstatin controls, whereas the other groups that received statins showed higher arthritic scores. Atorvastatin administration, especially before CIA induction, increased anti-CII autoantibody production. IL-2 and IL-17 production by lymph node and spleen cells was higher in CIA animals than in PBS controls, but was not affected by statin administration. While IFNγ production was not affected by CIA induction, atorvastatin administration before CIA induction increased the production of this cytokine.ConclusionThese data support previous results from our observational studies, indicating a role for statins in the induction of autoimmunity.

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“…Previously, we observed in a population-based study that statins were associated with an increased risk of developing RA [4]. Furthermore, cases of statin-associated lupus-like syndrome, dermatomyositis, and vasculitis have been reported [5]–[11] Moreover, in a study comprising data from spontaneous case reports we have found an association between statin use and the occurrence of a lupus-like syndrome [12].…”

Section: Introductionmentioning

confidence: 80%

Statin-Associated Polymyalgia Rheumatica. An Analysis Using WHO Global Individual Case Safety Database: A Case/Non-Case Approach

et al. 2012

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Objective To assess whether there is an association between statin use and the occurrence of polymyalgia rheumatic (PMR) in the spontaneous reporting database of the World Health Organisation (WHO). Methods We conducted a case/non-case study based on individual case safety reports (ICSR) in the WHO global ICSR database (VigiBase). Case reports containing the adverse event term polymyalgia rheumatica (WHOART or MedDRA Preferred Term) were defined as cases. Non-cases were all case reports containing other adverse event terms. Each case was matched to five non-cases by age, gender, and time of reporting. Case reports regarding a statin as suspected or concomitant drug were identified using the Anatomical Therapeutic Chemical (ATC) classification. Multivariate logistic regression was used to calculate reporting odds ratios (RORs) with 95% confidence intervals (CI). Results We identified 327 reports of PMR as cases and 1635 reports of other ADRs as non-cases. Among cases, statins were more frequently reported as suspected agent (29.4%) compared to non-cases (2.9%). After adjustment for several covariates, statins were significantly associated with reports of PMR (ROR 14.21; 95% CI 9.89–20.85). Conclusion The results of this study lends support to previous anecdotal case reports in the literature suggesting that the use of a statin may be associated with the occurrence of PMR. Further studies are needed to study the strength of the association in more detail and to elucidate the underlying mechanism.

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Association Between Statin Use and Lupus-Like Syndrome Using Spontaneous Reports

Cited by 29 publications

References 39 publications

Pattern of risks of systemic lupus erythematosus among statin users: a population-based cohort study

Pattern of risks of systemic lupus erythematosus among statin users: a population-based cohort study

Statins accelerate the onset of collagen type II-induced arthritis in mice

Statin-Associated Polymyalgia Rheumatica. An Analysis Using WHO Global Individual Case Safety Database: A Case/Non-Case Approach

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