Predictors of Response to Tofacitinib Treatment in Rheumatoid Arthritis Patients

Remission is defined as DAS28-4 CRP less than (<) 2.6 and DAS28-4 CRP < 3.2 corresponds to LDA. DAS28-4 CRP is a composite endpoint, calculated using 4 variables (represented by '-4' in the name). It includes components: tender joint count (TJC) and swollen joint count ((SJC) [both out of 28 evaluated joints], CRP milligram per liter (mg/l) and Patient's Global Assessment of Arthritis Disease Activity (PtGA) recorded on 100 millimeter (mm) visual analogue scale (VAS) (scores ranging 0 [no disease activity] to 100 mm [maximum disease activity], higher scores=more disease activity). DAS28-4 CRP is calculated as: 0.56 * square root (sqrt) (TJC) + 0.28 * sqrt (SJC) + 0.36 * ln (CRP+1) + 0.014*PtGA + 0.96; where ln = natural logarithm.

Remission is defined as DAS28-4 CRP < 2.6 and DAS28-4 CRP < 3.2 corresponds to LDA. DAS28-4 CRP is a composite endpoint, calculated using 4 variables (represented by '-4' in the name). It includes components: TJC and SJC assessed using 28 joints, CRP (mg/l) and PtGA recorded on 100 mm VAS scores ranging 0 [no disease activity] to 100 mm [maximum disease activity], higher scores=more disease activity). DAS28-4 CRP is calculated as: 0.56 * (sqrt) (TJC28) + 0.28 * sqrt (SJC28) + 0.36 * ln (CRP+1) + 0.014*PtGA + 0.96; where ln = natural logarithm.

DAS28-4 CRP is a composite endpoint, calculated using 4 variables (represented by '-4' in the name). It includes components: TJC and SJC both assessed using 28 joints, CRP (mg/l) and PtGA recorded recorded on VAS scores (mm). DAS28-4 CRP is calculated as: 0.56 * sqrt (TJC28) + 0.28 * sqrt (SJC28) + 0.36 * ln (CRP+1) + 0.014*PtGA + 0.96; where ln = natural logarithm. DAS28-4 CRP is a composite endpoint, calculated using 4 variables (represented by '-4' in the name). It includes components: TJC and SJC both assessed using 28 joints, ESR using mm/ hour and PtGA in recorded on VAS (mm). DAS28-4 ESR is calculated as: 0.56*sqrt (TJC28) + 0.28*sqrt (SJC28) + 0.70*In (ESR) + 0.014*PtGA where In = natural logarithm. The calculated range of DAS28-4 CRP and DAS 28-4 ESR is 0 (no disease activity) to 10 (maximal disease activity). A decrease from baseline in score indicates improvement of disease activity.

HAQ-DI is a participant-reported assessment which assess the degree of difficulty a participant had experienced during the last week in 8 domains/categories of daily living activities: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and other activities. Each activity category consists of 2 to 3 items. Each item is scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Any activity requiring assistance from another individual or the use of an assistive device adjusts to a minimum score of 2 to represent a more limited functional status. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score ranges from 0 to 3, where 0 indicates least difficulty and 3 indicates extreme difficulty.

Remission is defined as SDAI <=3.3. SDAI is a composite end point, calculated at each time point using the formula: as TJC + SJC both assessed using 28 joints + PtGA (assessed on 100 mm VAS scores ranging 0 [no disease activity] to 100 mm [maximum disease activity], higher scores=more disease activity) + Physician's Global Assessment of Health [PhGA] (assessed on 100 mm VAS scores ranging 0 [no disease activity] to 100 mm [maximum disease activity], higher scores=more disease activity)+ CRP (mg/dL).

Remission is defined as CDAI <=2.8. CDAI is a composite end point, calculated based on each time-point using TJC + SJC both assessed using 28 joints + PtGA (assessed on 100 mm VAS scores ranging 0 [no disease activity] to 100 mm [maximum disease activity], higher scores=more disease activity) + PhGA (assessed on 100 mm VAS scores ranging 0 [no disease activity] to 100 mm [maximum disease activity], higher scores=more disease activity).

DAS28-4 ESR is a composite endpoint, calculated using 4 variables (represented by '-4' in the name). Components includes: TJC, SJC both assessed using 28 joints, ESR (mm/h) and PtGA (mm) (recorded on 100 mm VAS scores ranging 0 [no disease activity] to 100 mm [maximum disease activity], higher score indicates high disease activity). The calculation of DAS28-4 ESR is as follows: 0.56 * sqrt (TJC28) + 0.28 * sqrt (SJC28) + 0.70* In (ESR) + 0.014* (PtGA); where ln = natural logarithm. DAS28-4 (ESR) score of <2.6 indicates remission.

DAS28-4 CRP is a composite endpoint, calculated using 4 variables (represented by '-4' in the name). Components includes: TJC, SJC both assessed using 28 joints, CRP (mg/l) and PtGA (mm) (recorded on 100 mm VAS scores ranging 0 [no disease activity] to 100 mm [maximum disease activity], higher score indicates high disease activity). The calculation of DAS28-4 CRP is as follows: 0.56 * sqrt (TJC) + 0.28 * sqrt (SJC) + 0.36 * ln (CRP+1) + 0.014*PtGA + 0.96; where ln = natural logarithm. DAS28-4 (CRP) score of <2.6 indicates remission.

LDA is defined as SDAI <=11. SDAI is a composite end point, calculated at each time point using the formula: as TJC + SJC (both assessed using 28 joints) + PtGA (assessed on 100 mm VAS scores ranging 0 [no disease activity] to 100 mm [maximum disease activity], higher scores=more disease activity) + PhGA (assessed on 100 mm VAS scores ranging 0 [no disease activity] to 100 mm [maximum disease activity], higher scores=more disease activity)+ CRP (mg/dL).

LDA is defined as CDAI <=10. CDAI is a composite end point, calculated based on each time-point using TJC + SJC (both assessed using 28 joints) + PtGA (assessed on 100 mm VAS scores ranging 0 [no disease activity] to 100 mm [maximum disease activity], higher scores=more disease activity) + PhGA (assessed on 100 mm VAS scores ranging 0 [no disease activity] to 100 mm [maximum disease activity], higher scores=more disease activity.

DAS28-4 ESR is a composite endpoint, calculated using 4 variables (represented by '-4' in the name). Components includes: TJC, SJC (both assessed using 28 joints), ESR (mm/h) and PtGA (recorded on 100 mm VAS scores ranging 0 [no disease activity] to 100 mm [maximum disease activity], higher score indicates high disease activity). The calculation of DAS28-4 ESR is as follows: 0.56 * sqrt (TJC28) + 0.28 * sqrt (SJC28) + 0.70* In(ESR) + 0.014* (PtGA); where ln = natural logarithm. DAS28-4 (ESR) score of <3.2 indicates LDA.

LDA is defined as DAS28-4(CRP) score of <3.2. DAS28-4 CRP is a composite endpoint, calculated using 4 variables (represented by '-4' in the name). It includes components: TJC, SJC (both assessed using 28 joints), CRP (mg/l) and PtGA (mm) (recorded on 100 mm VAS scores ranging 0 [no disease activity] to 100 mm [maximum disease activity], higher scores=more disease activity). The calculation of DAS28-4 CRP is as follows: 0.56*sqrt (TJC) + 0.28*sqrt (SJC) + 0.36*ln (CRP+1) + 0.014*PtGA + 0.96; where ln = natural logarithm. DAS28-4 (CRP) score of <3.2 indicates LDA.

HAQ-DI is a participant-reported assessment which assess the degree of difficulty a participant had experienced during the last week in 8 domains/categories of daily living activities: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and other activities. Each activity category consists of 2 to 3 items. Each item is scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Any activity requiring assistance from another individual or the use of an assistive device adjusts to a minimum score of 2 to represent a more limited functional status. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score ranges from 0 to 3, where 0 indicates least difficulty and 3 indicates extreme difficulty. A HAQ-DI response is defined as a decrease from baseline of at least 0.22.

EQ-5D is a standardized instrument used to measure quality of life. It is based on five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has three responses and the participant is asked to select the response that best describes them. The responses are scored 1-3 where 1 indicates no problems, 2 indicates some problems and 3 indicates unable to perform normal activities. The score (1 to 3), for each dimension is weighted based on United Kingdom (UK) data (Dolan et al 1995). An algorithm was applied to calculate the total EQ-5D health state score. Maximum and minimum score value were 1 and -0.6 respectively. Higher score indicates better health state.

FACIT-fatigue questionnaire score consists of 13 self-evaluated questions. Each question is scored from 0 to 4; the sum of all responses resulted in the FACIT-fatigue score of 0 (maximum fatigue) to 52 (no fatigue). A higher score represents better participant status.

The duration of morning stiffness is determined by asking the following questions: "Over the last 2 days, when did you wake in the morning? Over the last 2 days, when were you able to resume your normal activities without stiffness?". Time elapsed when participant woke up in morning and was able to resume normal activities without stiffness in minutes.

WPAI: 6-item questionnaire & scores are derived for four domains:absenteeism, presenteeism,work productivity loss & activity impairment.Question (Q)2 asked participants to indicate number of hours missed due to health problems in past 7 days. Q4 asked participants to indicate number of hours they worked in past 7 days.Q5 asked participants the degree to which their health affected productivity while working in past 7 days,on scale ranging from 0-10, Where 0 = health problems had no effect on their work & 10=health problems completely prevented participant from working. Q6 asked participants to indicate the degree to which their health affected their regular activities in past 7 days.Absenteeism=(Q2/[Q2 + Q4])*100.Presenteeism=(Q5/10)*100.Work Production Loss={(Q2/[Q2 + Q4])+(1-[Q2/(Q2 + Q4))*(Q5/10 )]}*100.Activity Impairment=(Q6/10)*100.Each WPAI domain is expressed as impairment percentages ranging from 0 to 100,with higher numbers indicating greater impairment &less productivity.

Participant's satisfaction with treatment was assessed on a 5-point scale (where 0 = very dissatisfied and 4 = very satisfied) in response to the question "How satisfied are you with the drugs you received for your arthritis during the last year?"

PtGA of Arthritis was measured using a VAS scores ranging 0 [no disease activity] to 100 mm [maximum disease activity], higher scores=more disease activity in response to the question "Considering all the way your arthritis affects you, how are you feeling today?".

PhGA was measured using a VAS scores ranging 0 [no disease activity] to 100 mm [maximum disease activity], higher scores=more disease activity in response to how the physician assesses the participant's overall arthritis at the time of the visit. This is an evaluation based on the participant's disease signs, functional capacity and physical examination, and should be independent of the PtGA of arthritis.

Number of participants who received tofacitinib as monotherapy,tofacitinib in combination therapy, tofacitinib switched from monotherapy to combination therapy, tofacitinib switched from combination therapy to monotherapy, tofacitinib in combination with disease modifying antirheumatic drugs (DMARD) then switched to tofacitinib monotherapy and tofacitinib in combination with DMARD then discontinued are presented in this outcome measure.

The study consisted of 4 visits. Baseline (visit 1), Month 3 (visit 2), Month 6 (visit 3), Month 12 (final or close out visit). The number of visits to a rheumatologist or other RA specialist since the last visit were reported in this outcome measure.

The study consisted of 4 visits. Baseline (visit 1), Month 3 (visit 2), Month 6 (visit 3), Month 12 (final or close out visit). Number of participants who underwent the diagnostic tests since last visit including: whole blood cell (WBC), ESR/CRP, glucose, hepatic enzymes, urea, creatinine, lipid profile (total cholesterol [TC], low density lipoprotein [LDL], high density lipoprotein [HDL], triglycerides [TG]), X-rays, others are presented.

The study consisted of 4 visits. Baseline (visit 1), Month 3 (visit 2), Month 6 (visit 3), Month 12 (final or close out visit). Number of participants who underwent the diagnostic tests including: WBC, ESR/CRP, glucose, hepatic enzymes, urea, creatinine, lipid profile (TC,LDL,HDL,TG), X-rays, others summarized by visit are presented.

The study consisted of 4 visits. Baseline (visit 1), Month 3 (visit 2), Month 6 (visit 3), Month 12 (final or close out visit). Diagnostic tests performed were as follow: WBC, ESR/CRP, glucose, hepatic enzymes, urea, creatinine, lipid profile (TC, LDL, HDL, TG), X-rays, others summarized by visit are presented.

The study consisted of 4 visits. Baseline (visit 1), Month 3 (visit 2), Month 6 (visit 3), Month 12 (final or close out visit). Number of participants hospitalized since their last visit were reported in this outcome measure.

The study consisted of 4 visits. Baseline (visit 1), Month 3 (visit 2), Month 6 (visit 3), Month 12 (final or close out visit). Number of participants hospitalized in daycare and nightcare since their last visit were reported in this outcome measure.

The study consisted of 4 visits. Baseline (visit 1), Month 3 (visit 2), Month 6 (visit 3), Month 12 (final or close out visit). Mean number of days participants were hospitalized since last visit were reported in this outcome measure.

The study consisted of 4 visits. Baseline (visit 1), Month 3 (visit 2), Month 6 (visit 3), Month 12 (final or close out visit). Number of participants according to reason for hospitalization: polyarthritis, RA and pericarditis, RA flare, and right knee arthroplasty due to osteoarthritis since their last visit is presented in this outcome measure.