Background/Purpose: HMG -CoA reductase inhibitors (statins) are standard treatment for hyperlipidemia. In addition to lipid lowering abilities, statins exhibit multiple anti-inflammatory effects.   The objectives of this study were to determine if treatment of patients with Rheumatoid Arthritis (RA) with lovastatin decreased CRP or reduced disease activity.

Methods: We conducted a randomized double blind placebo controlled 12 week trial.  64 patients with mildly active RA (defined as 2-8 tender joints and 1-6 swollen joints) and an elevated CRP (> 5mg/L) were randomized (1:1) to receive lovastatin 80mg or placebo.   Patients could be on stable prednisone ≤ 10 mg, DMARDs and/or biologic therapy.  The primary efficacy endpoint was the reduction in mean log CRP.  Secondary endpoints included disease activity, RF and anti-CCP antibody titers.  Safety was a co-primary endpoint; hepatic and muscle toxicities were of particular interest.

Results: Baseline features of the treatment groups were similar.  The mean baseline CRP was 12.2 mg/L in the lovastatin arm and 12.6 mg/L in the placebo arm; mean baseline DAS-28 CRP was 3.5 and 3.6 in the lovastatin and placebo arms, respectively.  No significant differences in mean log CRP reduction or % change in CRP from baseline between the two treatment arms were observed.  No significant difference between the lovastatin and placebo arms was observed in a longitudinal model of the estimated mean log CRP.  Disease activity assessed by DAS28 did not change from baseline in either lovastatin or placebo treated groups (-0.42 and -0.58, respectively, ns).  At week 12, clinical responses were comparable in subjects receiving lovastatin or placebo:  ACR 20 (29% vs. 40%) and Good/Moderate EULAR response (42% vs. 44%).  Autoantibody titers were stable during the course of the study with no group differences.  Although not statistically different, the frequency of subjects receiving biologic therapy was greater in the lovastatin treated group than placebo (59% vs. 38%).  A post-hoc analysis of subjects not using biologic therapy (n=32) demonstrated a significantly greater proportion achieving ≥15% reduction in CRP from baseline in the lovastatin treated group (83%) compared to placebo (33%; p = 0.019).  No analogous difference was observed in subjects receiving biologics (47% vs. 60%).  The mean change from baseline CRP in subjects not using biologics was also numerically greater in subjects taking lovastatin (-4.75) than placebo (-2.00).   Lovastatin was well tolerated with no serious safety concerns.  Several subjects experienced transient reversible elevations of transaminases. Clinical myositis was not observed.

Conclusion: Statins were well tolerated in our patient population.   This study showed no anti-inflammatory or clinical effects after 12 weeks of treatment with lovastatin.  However, we observed a potential modest effect of lovastatin in subjects not using biologics, suggesting statins may be anti-inflammatory in selected patients.

Sponsored by NIAID Autoimmunity Centers of Excellence:  U19 AI056362, U19AI056363; NCT00710021

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-double-blind-randomized-placebo-controlled-trial-of-lovastatin-in-patients-with-rheumatoid-arthritis/