Study Of The Effects Of Atorvastatin On Cholesterol Levels In Rheumatoid Arthritis Patients Taking CP-690,550

• Change From Baseline in Low Density Lipoprotein-Cholesterol (LDL-C) at Week 12 [ Time Frame: Baseline (Week 6), Week 12 ] [ Designated as safety issue: No ]
• 12-Hours Fasting Lipid Profile [ Time Frame: Day 0, Week 2, 6 (Baseline), 10, 12 ] [ Designated as safety issue: No ]
  Participants were required to fast for 12 hours prior to sampling for lipid profile which included following parameters: LDL-C, high-density lipoprotein-cholesterol (HDL-C), very low density lipoprotein-cholesterol (VLDL-C), total cholesterol, apolipoprotein A-1, apolipoprotein B, triglycerides (TGs) and Non-HDL-C.
• 12-Hours Fasting Lipid Profile: Particle Size of Lipoproteins [ Time Frame: Day 0, Week 2, 6 (Baseline), 10, 12 ] [ Designated as safety issue: No ]
  Participants were required to fast for 12 hours prior to sampling for lipid profile which included following parameters: plasma lipoprotein VLDL-C, LDL-C and HDL-C particles size.
• 12-Hours Fasting Lipid Profile: Level of Lipoprotein Particles [ Time Frame: Day 0, Week 2, 6 (Baseline), 10, 12 ] [ Designated as safety issue: No ]
  Participants were required to fast for 12 hours prior to sampling for lipid profile which included following parameters: total and large VLDL-C and chylomicron particles (VLDLCP), medium and small VLDL-C particles; total, large, medium and small LDL-C particles; and intermediate density lipoprotein (IDL).
• 12-Hours Fasting Lipid Profile: Level of High Density Lipoprotein Cholesterol (HDL-C) Particles [ Time Frame: Day 0, Week 2, 6 (Baseline), 10, 12 ] [ Designated as safety issue: No ]
  Participants were required to fast for 12 hours prior to sampling for lipid profile which included following parameters: total, large, medium and small HDL-C particles.
• Disease Activity Score Using 28-Joint Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) [ Time Frame: Day 0, Week 6 (Baseline), 12 ] [ Designated as safety issue: No ]
  DAS28-3 (CRP) was calculated from the number of swollen joints (SJC) and painful joints (PJC) using the 28 joints count and the CRP (milligram per liter [mg/L]). DAS28-3 (CRP) less than or equal to (<=)3.2 indicated low disease activity, DAS28-3 (CRP) more than (>) 3.2 to 5.1 indicated moderate to high disease activity.
• Disease Activity Score Using 28-Joint Count and C-Reactive Protein (4 Variables) (DAS28-4 [CRP]) [ Time Frame: Day 0, Week 6 (Baseline), 12 ] [ Designated as safety issue: No ]
  DAS28-4 (CRP) was calculated from the number of swollen joints (SJC) and painful joints (PJC) using the 28 joints count, C-reactive protein (CRP) [mg/L] and patient's global assessment (PtGA) of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28-4 [CRP] <=3.2 indicated low disease activity, DAS28-4 [CRP] >3.2 to 5.1 indicated moderate to high disease activity and DAS28 less than 2.6 indicates remission.
• Disease Activity Score Using 28-Joint Count and Erythrocyte Sedimentation Rate (3 Variables) (DAS28-3 [ESR]) [ Time Frame: Day 0, Week 6 (Baseline), 12 ] [ Designated as safety issue: No ]
  DAS28-3 (ESR) was calculated from the number of swollen joints (SJC) and painful joints (PJC) using the 28 joints count and the erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hr]). DAS28-3 (ESR) <=3.2 indicated low disease activity, DAS28-3 (ESR) >3.2 to 5.1 indicated moderate to high disease activity.
• Disease Activity Score Using 28-Joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) [ Time Frame: Day 0, Week 6 (Baseline), 12 ] [ Designated as safety issue: No ]
  DAS28-4 (ESR) was calculated from the number of swollen joints (SJC) and painful joints (PJC) using the 28 joints count, the erythrocyte sedimentation rate (ESR) [mm/hr] and patient's global assessment (PtGA) of disease activity (participant rated arthritis activity assessment with transformed scores ranging from 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28-4 (ESR) <=3.2 indicated low disease activity, DAS28-4 (ESR) >3.2 to 5.1 indicated moderate to high disease activity.
• Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response [ Time Frame: Week 6 (Baseline), 12 ] [ Designated as safety issue: No ]
  ACR20 responses were defined as greater than or equal to 20% improvement in tender or swollen joint counts and 20% improvement in 3 of the 5 remaining ACR-core set measures: 1) physician's global assessment of disease activity, 2) participants assessment of disease activity, 3) participants assessment of pain, 4) participants assessment of functional disability via a health assessment questionnaire, and 5) C-reactive protein at each visit.
• Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response [ Time Frame: Week 6 (Baseline), 12 ] [ Designated as safety issue: No ]
  ACR50 responses were defined as greater than or equal to 50% improvement in tender or swollen joint counts and 50% improvement in 3 of the 5 remaining ACR-core set measures: 1) physician's global assessment of disease activity, 2) participants assessment of disease activity, 3) participants assessment of pain, 4) participants assessment of functional disability via a health assessment questionnaire, and 5) C-reactive protein at each visit.
• Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response [ Time Frame: Week 6 (Baseline), 12 ] [ Designated as safety issue: No ]
  ACR70 responses were defined as greater than or equal to 70% improvement in tender or swollen joint counts and 70% improvement in 3 of the 5 remaining ACR-core set measures: 1) physician's global assessment of disease activity, 2) participants assessment of disease activity, 3) participants assessment of pain, 4) participants assessment of functional disability via a health assessment questionnaire, and 5) C-reactive protein at each visit.
• Tender-Joint Count [ Time Frame: Day 0, Week 6 (Baseline), 12 ] [ Designated as safety issue: No ]
  Tender joint count (TJC) is an assessment of 68 joints (upper body, upper extremity, and lower extremity). Each joint's response to pressure/motion was assessed using the following scale: Present/Absent/Not Done/Not Applicable (for artificial joints).
• Swollen-Joint Count [ Time Frame: Day 0, Week 6 (Baseline), Week 12 ] [ Designated as safety issue: No ]
  Swollen joint count (SJC): an assessment of 66 joints (upper body, upper extremity, and lower extremity). Each joint was assessed for swelling using the following scale: Present/Absent/Not Done/Not Applicable (for artificial joints).
• C-Reactive Protein (CRP) [ Time Frame: Day 0, Week 6 (Baseline), 12 ] [ Designated as safety issue: No ]
  The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation. Normal range is 1-3 milligram per liter (mg/L).
• Erythrocyte Sedimentation Rate (ESR) [ Time Frame: Day 0, Week 6 (Baseline), 12 ] [ Designated as safety issue: No ]
  ESR is a laboratory test that provides a non-specific measure of inflammation. The test assesses the rate at which red blood cells fall in a test tube. Normal range is 0-30 mm/hr. A higher rate is consistent with inflammation.
• Patient Assessment of Arthritis Pain [ Time Frame: Day 0, Week 6 (Baseline), 12 ] [ Designated as safety issue: No ]
  Participants assessed the severity of their arthritis pain using a 100 millimeter (mm) visual analog scale (VAS). The scale ranged from 0 (no pain) to 100 (most severe pain), measurement on a scale corresponds to the magnitude of their pain.
• Physician's Global Assessment (PhysGA) of Arthritis Pain [ Time Frame: Day 0, Week 6 (Baseline), Week 12 ] [ Designated as safety issue: No ]
  The physician evaluated participants disease signs, functional capacity and physical examination independent of the patient's global assessment of arthritis. Physician's response was recorded using 0-100 mm visual analog scale (VAS), where 0=no pain and 100=most severe pain.
• Patient's Global Assessment (PtGA) of Arthritis Pain [ Time Frame: Day 0, Week 6 (Baseline), Week 12 ] [ Designated as safety issue: No ]
  Participants answered: "Considering all the ways your arthritis affects you, how are you feeling today?" Participants responded by using a 0-100 mm visual analog scale where 0=no pain and 100=most severe pain.
• Health Assessment Questionnaire Disability Index (HAQ-DI) [ Time Frame: Day 0, Week 6 (Baseline), 12 ] [ Designated as safety issue: No ]
  HAQ-DI: participant-reported assessment of ability to perform tasks in 8 functional categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3, 0=least functional difficulty and 3=extreme functional difficulty.

• Absolute change in LDL level compared to baseline (Week 6) [ Time Frame: Week 12 ] [ Designated as safety issue: Yes ]
• 12-hour fasting lipids, including but not limited to total cholesterol, LDL C, HDL C, VLDL C, non HDL C, apolipoproteins A 1 and B, lipoprotein particle size and pool size and triglycerides [ Time Frame: At each timepoint ] [ Designated as safety issue: Yes ]
• RA related efficacy endpoints including DAS28 3 and DAS28 4 (CRP and ESR), ACR response rates and their components: joint counts, HAQ DI, patient & physician VAS scales, CRP and ESR [ Time Frame: Pretreatment, Wk 6 and Wk 12 ] [ Designated as safety issue: No ]
• Clinical safety laboratory testing (hematology, chemistry, urinalysis), physical exam and vital signs (complete & targeted physical examination, electrocardiogram, blood pressure and temperature), and assessment of adverse events [ Time Frame: At each timepoint ] [ Designated as safety issue: Yes ]

All patients will be in instructed to eat a therapeutic lifestyle diet and will receive CP-690,550 throughout the 12 weeks of this study. After 6 weeks, half will receive the cholesterol lowering agent, atorvastatin, and half a matching placebo. This study will first measure the effects of CP-690,550 on cholesterol levels and then the effects of adding atorvastatin on those levels.

• Drug: CP-690,550
  12 week open-label CP-690,550 10 mg oral tablets administered twice daily starting at Day 0 through Week 12
• Drug: Atorvastatin
  Starting at Week 6 and continuing through Week 12 atorvastatin 10 mg oral tablets administered once daily
• Drug: Atorvastatin Placebo
  Starting at Week 6 and continuing through Week 12 atorvastatin placebo tablets administered once daily

• Experimental: Arm 1
  Interventions:

  • Drug: CP-690,550
  • Drug: Atorvastatin
• Experimental: Arm 2
  Interventions:

  • Drug: CP-690,550
  • Drug: Atorvastatin Placebo

Inclusion Criteria:

• must be diagnosed as having active rheumatoid arthritis
• agree to participate in the study and sign and informed consent document

Exclusion Criteria:

• History of serious infection within the past 6 months
• test positive for TB
• have any uncontrolled clinically significant disease or laboratory tests
• require administration of prohibited medications during the study