Long-Term Effectiveness And Safety Of CP-690,550 For The Treatment Of Rheumatoid Arthritis

Criteria for laboratory abnormalities: hemoglobin (Hg), hematocrit, red blood cell (RBC), high density lipoprotein (HDL) cholesterol:\<0.8\*lower limit of normal (LLN), platelet\<0.5\*LLN/\>1.75\*upper limit of normal (ULN), white blood cell (WBC)\<0.6\*LLN/\>1.5\*ULN, lymphocyte, neutrophil, protein, albumin \<0.8\*LLN/\>1.2\*ULN, basophil, eosinophil, monocyte, low density lipoprotein (LDL) cholesterol: \>1.2\*ULN; bilirubin\>1.5\*ULN, aspartate amino transferase(AT), alanine AT, gammaglutamyl transferase, alkaline phosphatase:\>3.0\*ULN; blood urea nitrogen, creatinine, cholesterol, triglyceride:\>1.3\*ULN; sodium \<0.95\*LLN/\>1.05\*ULN, potassium, chloride, calcium, bicarbonate: \<0.9\*LLN/\>1.1\*ULN; glucose\<0.6\*LLN/\>1.5\*ULN; Urine (specific gravity\<1.003/\>1.030, pH\<4.5/\>8, glucose, ketone, protein, blood/Hg(\>=1; RBC, WBC\>=20; creatinine kinase\>2\*ULN).

Time frame: Baseline (Day 1 at Entry of Extension Period) up to 28 days after last study drug dose in Extension Period (13 Months)

Population: Safety analysis set included all participants who enrolled for extension period and received at least 1 dose of open label study medication in extension period.

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pretreatment state. AEs included both serious and non-serious adverse events.

Time frame: Baseline (Day 1 at Entry of Extension Period) up to 28 days after last study drug dose in Extension Period (13 Months)

Population: Safety analysis set included all participants who enrolled for extension period and received at least 1 dose of open label study medication in extension period.

Long term safety and tolerability of Tofacitinib was measured as following: percentage (%) of participants with AEs, percentage of participants who discontinued due to AEs. An AE is any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship.

Time frame: Baseline (Day 1 at Entry of Extension Period) up to Month 6 of Extension Period; Month 6 of Extension Period to Month 12 of Extension Period

Population: Safety analysis set included all participants who enrolled for extension period and received at least 1 dose of open label study medication in extension period. Here, Number Analyzed signifies number of participants evaluable for specified categories.

Treatment-emergent non serious AEs by System Organ Class (SOC) (all causalities) and Laboratory Test Abnormalities (without regard to baseline) The stated number of participants analyzed was the total number of participants in each group (AEs). The actual number of participants analyzed for each laboratory parameter varied, and is provided for each. Abs=absolute; ALT=alanine aminotransferase; AST=aspartate aminotransferase; ESR=erythrocyte sedimentation rate; GGT=gamma glutamyl transferase; hgb=hemoglobin; HDL=high density lipids; LDL=low density lipids; LLN=lower limit of normal; qual=qualitative; Tot=total; ULN=upper limit of normal; WBC=white blood cell

Time frame: Includes laboratory test abnormality data for all visits and adverse event data up to 999 days after last dose of study drug

Population: For abnormal laboratory results, those listed include both mandatory and optional laboratory tests. The number of participants analyzed is the number with at least one evaluable observation of the given laboratory test. Fasting lipids were only collected from participants who enrolled more than 14 days after last visit of their qualifying study.

Treatment-emergent AEs by SOC (all causalities) - all participants, by time. Data presented for Post Month 96 includes data up to and including Month 114.

Time frame: Includes AEs for every visit and up to 999 days after last dose of study drug

Population: The stated number of participants analyzed is the total number of participants enrolled in each group. The number of evaluable participants is the number remaining in the study in the given time period.

DAS28 is composite score, calculated using mathematical formula, derived from: 1) tender/painful joints count, out of 28 joints (TJC28), 2) swollen joints count, out of 28 joints (SJC28), 3) blood marker of inflammation (ESR \[millimeter per hour\] or CRP \[milligram per liter\]). DAS28-4 also include score of general health (GH). GH is general health or participants' global assessment of disease activity on 100 mm visual analog scale (GH score: 0 mm \[very well\] to 100 mm \[extremely bad\], higher scores = worse health condition). DAS28-3(CRP) = (0.56\*sqrt\[TJC28\] + 0.28\*sqrt\[SJC28\] + 0.36\*ln\[CRP+1\]) \*1.10 + 1.15) and DAS28-4(ESR) = (0.56\*sqrt\[TJC28\] + 0.28\*sqrt\[SJC28\] + 0.70\*ln\[ESR\] + 0.014\*GH), where sqrt = square root, ln = natural logarithm. DAS28-4 ESR and DAS28-3 CRP: score ranges from 0 (none) to 9.4 (extreme disease activity), with a higher score indicating more disease activity. Score of \<=3.2 indicate low disease activity and score of \<2.6 indicate disease remission.

Time frame: Baseline (Month 0 at the entry of Initial period); Month 3, 6, 9 and 12 of Extension Period

Population: Full analysis set included all participants who enrolled for extension period and received at least 1 dose of open label study medication in extension period. Here, Number Analyzed signifies number of participants who were evaluable for specified categories.

HAQ-DI assesses the degree of difficulty a participant has experienced during the past week in 8 categories of daily living activities: dressing/grooming; arising; eating; walking; reach; grip; hygiene; and other activities. Each activity category consisted of 2-3 questionnaire. Each questionnaire was scored on a 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Any activity that required assistance from another individual or required the use of an assistive device was adjusted to a score of 2 to represent a more limited functional status. Overall score was computed as the sum of total scores divided by the number of questionnaire answered. Total possible HAQ-DI score range: 0 (least difficulty) and 3 (extreme difficulty), where higher scores indicate more difficulty while performing daily living activities.

Time frame: Baseline (Month 0 at the entry of Initial Period); Month 3, 6, 9, and 12 of Extension Period

Population: Full analysis set included all participants who enrolled for extension period and received at least 1 dose of open label study medication in extension period. Here, Number Analyzed signifies number of participants who were evaluable for specified categories.

ACR20=20 percent (%) improvement from baseline (Month 0 at entry of Initial Period) in tender/painful joint count and swollen joint count, and in at least 3 of 5 variables: participant's global assessment of arthritis (PtGA), physician's global assessment of arthritis (PGA), participant's assessment of arthritis pain (PtA), HAQ-DI, C-reactive protein. ACR50 is a 50% improvement and ACR70 is a 70% improvement in these variables. PtGA: participant assessed overall disease activity, score: 0 (no arthritis) to 10 (extreme arthritis), higher score=more arthritis. PGA: physician judged participant's overall disease activity, score: 0 (no arthritis) to 10 (extreme arthritis), higher score=more arthritis. PtA: participant assessed arthritis pain by 100 millimeter (mm) visual analogue scale, score: 0 mm (no pain) to 100 mm (extreme pain), higher score=more pain. HAQ-DI: functional disability evaluation, score: 0 (no difficulty) to 3 (extreme difficulty), higher score=more disability.

Time frame: Month 3, 6, 9 and 12 of Extension Period

Population: Full analysis set included all participants who enrolled for extension period and received at least 1 dose of open label study medication in extension period. Here, Number Analyzed signifies number of participants who were evaluable for specified categories.

DAS28 is composite score, calculated using mathematical formula, derived from: 1) tender/painful joints count, out of 28 joints (TJC28), 2) swollen joints count, out of 28 joints (SJC28), 3) blood marker of inflammation (ESR \[millimeter per hour\] or CRP \[milligram per liter\]). DAS28-4 also include score of GH. GH is general health or participants' global assessment of disease activity on 100 mm visual analog scale (GH score: 0 mm \[very well\] to 100 mm \[extremely bad\], higher scores = worse health condition). DAS28-3(CRP) = (0.56\*sqrt\[TJC28\] + 0.28\*sqrt\[SJC28\] + 0.36\*ln\[CRP+1\]) \*1.10 + 1.15) and DAS28-4(ESR) = (0.56\*sqrt\[TJC28\] + 0.28\*sqrt\[SJC28\] + 0.70\*ln\[ESR\] + 0.014\*GH), where sqrt = square root, ln = natural logarithm. DAS28-4 ESR and DAS28-3 CRP: score range is from 0 (none) to 9.4 (extreme disease activity), with a higher score indicating more disease activity. Score of \<=3.2 indicate low disease activity and score of \<2.6 indicate disease remission.

Time frame: Baseline (Day 1 at the entry of Extension period); Month 3, 6, 9 and 12 of Extension Period

Population: Full analysis set included all participants who enrolled for extension period and received at least 1 dose of open label study medication in extension period. Here, Number Analyzed signifies number of participants who were evaluable for specified categories.

No data were collected for this endpoint because it was removed from the protocol in a previous amendment.

Time frame: Not applicable as no data were collected for this endpoint.

Population: No data were collected for this endpoint as it was removed from the protocol in a protocol amendment.

Descriptive statistics for DAS28-3 (CRP) and DAS28-4 (ESR). The stated number of participants analyzed was the total number of participants in each group. The actual number of participants analyzed on each occasion varied, and is provided for each visit presented. DAS28 is a composite score, calculated using a mathematical formula, and is derived from the number of tender/painful joints (out of 28), number of swollen joints (out of 28), and a blood marker of inflammation (ESR or CRP). DAS28-4 also includes a score of general health in the formula. The score range is from 0 to 9.4, with a higher score indicating more disease activity. A score of \>5.1 indicates active disease, a score of ≤3.2 indicates low disease activity, and a score of \<2.6 indicates disease remission.

Time frame: Every visit until study completion

Population: The number of participants analyzed is the number remaining in the study who had evaluable data for the measure at the given time point.

Change from Baseline Scores for each: FACIT Fatigue Scale (score range 0 to 52, higher score indicates higher quality of life and an increase from baseline score indicates improvement), EuroQol EQ 5D (index values derived from a measure of central tendency and a measure of dispersion, an increase from baseline indicates improvement, score range 0 to 1), Work Limitations (WL) Physical Demands (covers ability to perform job tasks that involve bodily strength, a decrease from baseline indicates improvement, score range 0 to 100, higher scores indicating greater limitation), and RA Healthcare Resource Utilization Work Performance in Past 3 Months on Days Bothered by RA (assesses healthcare use over previous 3 months, a decrease from baseline indicates improvement, score range 0 to 10). The stated number of participants analyzed was the total number of participants in each group. The actual number of participants analyzed on each occasion varied, and is provided for each visit presented.

Time frame: Every visit until study completion

Population: The number of participants analyzed is the number remaining in the study who had evaluable data for the measure at the given time point.

Change from baseline by visit. HAQ-DI scores range from 0 to 3, where lower score implies less disease. A reduction from baseline in score indicates an improvement in condition. A clinically meaningful decrease from baseline is defined as a decrease of at least 0.22 units. The stated number of participants analyzed was the total number of participants in each group. The actual number of participants analyzed on each occasion varied, and is provided for each visit presented.

Time frame: Every visit until study completion

Population: The number of participants analyzed is the number remaining in the study who had evaluable data for the measure at the given time point.

Percent participants with DAS28-4 (ESR) \<2.6 and ≤3.2 and percent participants with DAS28-3 (CRP) \<2.6 and ≤3.2. The stated number of participants analyzed was the total number of participants in each group. The actual number of participants analyzed on each occasion varied, and is provided for each visit presented. DAS28 is a composite score, calculated using a mathematical formula, and is derived from the number of tender/painful joints (out of 28), number of swollen joints (out of 28), and a blood marker of inflammation (ESR or CRP). DAS28-4 also includes a score of general health in the formula. The score range is from 0 to 9.4, with a higher score indicating more disease activity. A score of \>5.1 indicates active disease, a score of ≤3.2 indicates low disease activity, and a score of \<2.6 indicates disease remission.

Time frame: Every visit until study completion

Population: Full Analysis Set - No Imputation. The number of participants analyzed is the number remaining in the study who had evaluable data for the measure at the given time point.