Abstract
This Hospital Pharmacy feature is extracted from Off-Label Drug Facts, a quarterly publication available from Wolters Kluwer Health. Off-Label Drug Facts is a practitioner-oriented resource for information about specific drug uses that are unapproved by the US Food and Drug Administration. This new guide to the literature will enable the health care professional or clinician to quickly identify published studies on off-label uses and determine if a specific use is rational in a patient care scenario. A summary of the most relevant data is provided, including background, study design, patient population, dosage information, therapy duration, results, safety, and therapeutic considerations. References direct the reader to the full literature for more comprehensive information before patient care decisions are made. Direct questions or comments regarding Off-Label Drug Uses to hospital
Background
Rheumatoid arthritis (RA), a disease characterized by chronic inflammatory arthropathy, typically results in significant functional impairment and decreased quality of life. The disease is also associated with an increased risk of morbidity and mortality from cardiovascular disease, specifically accelerated atherogenesis. Similarities exist between inflammation present in atherogenic lesions in the cardiovascular vessel and inflammation found in the chronic synovitis of RA. 1 Thus, the use of statins to improve markers of cardiovascular disease, as well as to promote control of RA, has been suggested.2,3 Although statin agents are indicated primarily for lipid modulation and reduction in cardiovascular morbidity and mortality, some data suggest that they also interfere with inflammation pathways and, thus, may be useful in broader applications.
Patient Population
Adults with active RA who have been taking disease-modifying antirheumatic drug (DMARD) therapy for at least 3 months.
Dosage and Duration
Administered orally as 20 mg daily for 3 months or 40 mg daily for 6 months.
Results
The use of atorvastatin in the treatment of RA has been evaluated primarily in a limited number of controlled and noncontrolled trials enrolling fewer than 150 patients.
Controlled Trial
The use of atorvastatin for the treatment of RA has been evaluated in 1 controlled trial. A total of 116 patients with active RA who had been taking DMARD therapy for at least 3 months were randomized for receipt of atorvastatin 40 mg or placebo daily for 6 months. At baseline, significantly more patients in the atorvastatin group were taking methotrexate than in the placebo group (50% vs 26%; P = 0.0074). Other DMARD therapy included sulfasalazine (60% vs 64%), hydroxychloroquine (12% vs 22%), leflunomide (3% vs 9%), gold injections (7% vs 9%), penicillamine (2% vs 0%), and minocycline (2% vs 0%). Corticosteroid use was also varied and included prednisolone (3% vs 0%), intra-articular triamcinolone (21% vs 29%), or intramuscular triamcinolone (10% vs 19%). The primary outcome measurement was change in disease activity score from baseline to 6 months of therapy. At baseline, the atorvastatin group had less severe disease, as demonstrated by some parameters (eg, disease activity score, patient global assessment). At 6 months, the change in disease activity score was significantly greater in the atorvastatin group compared with the placebo group (-0.5 vs 0.03). In addition, significant changes occurred in the atorvastatin group for reduction in secondary outcome measures, including erythrocyte sedimentation rate, C-reactive protein (CRP), and swollen joint count. There were no differences between the groups for changes in tender joint count, early morning stiffness, visual analog score, patient global assessment, and health assessment. As expected, significant reductions also occurred in the atorvastatin group for cholesterol, triglycerides, and low-density lipoprotein (LDL) cholesterol. Other risk factors for cardiac disease, fibrinogen (-0.38 vs 0 g/L), plasma viscosity (-0.05 vs −0 mPa/s), and interleukin 6 (-6.6 vs 3.84 pg/mL) were reduced. This study had several limitations, including a wide variance between the groups' DMARD therapies and a small population sample. 4
Noncontrolled Trial
In a noncontrolled trial, 29 adults with RA took atorvastatin 20 mg daily for 12 weeks. As expected, significant reductions in total and LDL cholesterol were evident by week 6 and remained reduced at week 12. At the 6- and 12-week assessment, there were no significant changes in pulse rate, blood pressure, erythrocyte sedimentation rate, CRP, or disease activity score. The augmentation index, a measure of systemic arterial stiffness and a marker for vascular dysfunction, is calculated as the difference between the second and first systolic peaks and expressed as a percentage of pulse pressure. Arterial stiffness is also an independent risk factor for cardiovascular disease and may be a surrogate marker of cardiovascular disease in patients with RA. After 6 weeks of atorvastatin therapy, the augmentation index was significantly reduced when compared with baseline values, and it remained reduced at the 12-week assessment. Other measures of RA disease activity were unchanged throughout the 12-week study (eg, CRP, erythrocyte sedimentation rate, disease activity score). 5
Safety
This is a limited safety profile. Refer to package labeling for complete prescribing information (eg, Warnings/Precautions, Adverse Reactions, Drug Interactions).
Atorvastatin was well tolerated in reviewed studies. The overall incidence of adverse events was not significantly different between the groups. There was no evidence of muscle or liver function abnormalities in either study group. 4
Therapy Considerations
Initial results suggest that atorvastatin may affect markers for cardiac disease, as well as some parameters for clinical inflammatory changes, in patients with RA (eg, swollen joint count, disease activity score). However, larger, controlled trials with stricter controls for disease-state assessment and adjunctive therapy are needed before this therapy is established as effective.