A DOSE-RANGING STUDY TO EVALUATE EFFICACY AND SAFETY OF PF-06700841 IN SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)

SRI-4 components included Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), British Isles Lupus Assessment Group (BILAG) 2004 and Physician's Global Assessment (PhGA). Participants were classified as SRI-4 responders, if they met all of the following criteria compared with baseline: 1) greater than or equal to (>=) 4 point reduction in SLEDAI-2K score; 2) no new BILAG A organ domain score or 2 new BILAG B organ domain scores; 3) no worsening (less than [<] 0.3 point increase) in PhGA score. SLEDAI-2K: assesses improvement in disease activity (range: 0 to 105; higher score = higher severity). BILAG: assesses disease extent, severity in individual organ system (range: A [severe] to E [no disease]; higher score = less severity). PhGA: assesses worsening in participant's general health status (range: 0 [none] to 3 [severe]; higher score = higher severity).

BICLA included: BILAG-2004, SLEDAI-2K and PhGA. Participants were classified as responders, if they met all the following criteria: BILAG-2004 improvement (all A scores at baseline improved to B/C/D and all B scores improved to C or D); no worsening in disease activity (no new BILAG-2004 A scores or =<1 new B score); no worsening of total SLEDAI-2K score; no significant deterioration (<10 percent [%] worsening) in analogue PhGA. SLEDAI-2K: assesses improvement in disease activity (range: 0 to 105; higher score = higher severity). BILAG: assesses disease extent, severity in individual organ system (range: A [severe] to E [no disease]; higher score = less severity). PhGA: assesses worsening in participant's general health status (range: 0 [none] to 3 [severe]; higher score = higher severity).

LLDAS was defined as SLE disease activity index (SLEDAI-2k <=4, with no activity in major organ systems [renal, central nervous system, cardiopulmonary, vasculitis, fever]) and no haemolytic anaemia or gastrointestinal activity; no new lupus disease activity compared with the previous assessment; a Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)-SLEDAI PhGA (scale 0-3; higher scores = higher severity) <=1; a current prednisolone (or equivalent) dose <=7.5 milligram per day (mg/daily); and well tolerated standard maintenance doses of immunosuppressive drugs and approved biological agents.

In this outcome measure data is reported for participants who achieved a reduction in prednisone (or equivalent) dose to <=7.5 mg/day and sustained for 12 Weeks prior at Week 52 and they also sustained this dose reduction for 12 weeks prior to Week 52 (Week 40 to Week 52).

In this outcome measure data is reported for participants who achieved a reduction in SRI-4 response with prednisone dose reduced to <=7.5 mg/day and sustained for 12 weeks at Week 52.

CLASI is an validated measurement instrument for lupus erythematosus developed for use in clinical studies that consists of separate scores for the activity of the disease (CLASI-A). The CLASI activity score is calculated on the basis of erythema, scale/hyperkeratosis, mucous membrane involvement, acute hair loss and non-scarring alopecia. The CLASI activity score ranges from 0-70, with higher scores indicating more severe skin disease. Severity categories based on the CLASI activity score are as follows: mild (0-9), moderate (10-20), and severe (21-70).

The FACIT-F Scale is a participant completed questionnaire consisting of 13 items that assess fatigue. Participants responded to each item on a 5-point scale based on their experience of fatigue during the past 7 days (0 = not at all; 1 = a little bit; 2 =somewhat; 3 = quite a bit; 4 = very much). Instrument scoring yielded a range from 0 to 52 (negatively worded items were reversed during analysis), with higher scores representing better participant status (less fatigue).

The LupusQoL questionnaire is a validated questionnaire used to evaluate SLE -specific concepts of SLE as reported by participants. It consists of 34 items in 8 different domains: physical health, emotional health, body image, pain, planning, fatigue, intimate relationship, and burden to others; measured on a 5-point scale ranging from 0 (not at all) to 4 (very much). The individual domain scores are transformed to a 0 to 100 scale wherein higher scores indicate better quality of life. Physical health domain score of LupusQoL had score range from 0 to 100, where higher scores = better quality of life.

The LupusQoL questionnaire is a validated questionnaire used to evaluate SLE -specific concepts of SLE as reported by participants. It consists of 34 items in 8 different domains: physical health, emotional health, body image, pain, planning, fatigue, intimate relationship, and burden to others measured on a 5-point scale ranging from 0 (not at all) to 4 (very much). The individual domain scores are transformed to a 0 to 100 scale wherein higher scores indicate better quality of life. Emotional health domain score of LupusQoL had score range from 0 to 100, where higher scores = better quality of life.

The LupusQoL questionnaire is a validated questionnaire used to evaluate SLE -specific concepts of SLE as reported by participants. It consists of 34 items in 8 different domains: physical health, emotional health, body image, pain, planning, fatigue, intimate relationship, and burden to others measured on a 5-point scale ranging from 0 (not at all) to 4 (very much). The individual domain scores are transformed to a 0 to 100 scale wherein higher scores indicate better quality of life. Body image domain score of LupusQoL had score range from 0 to 100, where higher scores = better quality of life.

The LupusQoL questionnaire is a validated questionnaire used to evaluate SLE -specific concepts of SLE as reported by participants. It consists of 34 items in 8 different domains: physical health, emotional health, body image, pain, planning, fatigue, intimate relationship, and burden to others measured on a 5-point scale ranging from 0 (not at all) to 4 (very much). The individual domain scores are transformed to a 0 to 100 scale wherein higher scores indicate better quality of life. Pain domain score of LupusQoL had score range from 0 to 100, where higher scores = better quality of life.

The LupusQoL questionnaire is a validated questionnaire used to evaluate SLE -specific concepts of SLE as reported by participants. It consists of 34 items in 8 different domains: physical health, emotional health, body image, pain, planning, fatigue, intimate relationship, and burden to others measured on a 5-point scale ranging from 0 (not at all) to 4 (very much). The individual domain scores are transformed to a 0 to 100 scale wherein higher scores indicate better quality of life. Planning domain score of LupusQoL had score range from 0 to 100, where higher scores = better quality of life.

The LupusQoL questionnaire is a validated questionnaire used to evaluate SLE -specific concepts of SLE as reported by participants. It consists of 34 items in 8 different domains: physical health, emotional health, body image, pain, planning, fatigue, intimate relationship, and burden to others measured on a 5-point scale ranging from 0 (not at all) to 4 (very much). The individual domain scores are transformed to a 0 to 100 scale wherein higher scores indicate better quality of life. Fatigue domain score of LupusQoL had score range from 0 to 100, where higher scores = better quality of life.

The LupusQoL questionnaire is a validated questionnaire used to evaluate SLE -specific concepts of SLE as reported by participants. It consists of 34 items in 8 different domains: physical health, emotional health, body image, pain, planning, fatigue, intimate relationship, and burden to others measured on a 5-point scale ranging from 0 (not at all) to 4 (very much). The individual domain scores are transformed to a 0 to 100 scale wherein higher scores indicate better quality of life. Intimate relationship domain score of LupusQoL had score range from 0 to 100, where higher scores = better quality of life.

The LupusQoL questionnaire is a validated questionnaire used to evaluate SLE -specific concepts of SLE as reported by participants. It consists of 34 items in 8 different domains: physical health, emotional health, body image, pain, planning, fatigue, intimate relationship, and burden to others measured on a 5-point scale ranging from 0 (not at all) to 4 (very much). The individual domain scores are transformed to a 0 to 100 scale wherein higher scores indicate better quality of life. Burden to others domain score of LupusQoL had score range from 0 to 100, where higher scores = better quality of life.

Incidence rate was defined as the number of new events per 100 person-years.

An AE was any untoward medical occurrence in a participant who received study intervention without regard to possibility of causal relationship. TEAEs are events from first dose of study intervention to 4 weeks after last dose of study intervention that were absent before treatment or that worsened relative to pre-treatment state. An 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. AEs included both SAEs and all non-SAEs.

An AE was any untoward medical occurrence in a participant who received study intervention without regard to possibility of causal relationship. An 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.

An AE was any untoward medical occurrence in a participant who received study intervention without regard to possibility of causal relationship. In this outcome measure, participants with adverse events leading to discontinuation from study were reported.

Vital signs included blood pressure, pulse rate, respiratory rate, and temperature. Clinical significance in vital signs abnormalities was judged by investigator.

Clinical significance in ECG abnormalities was judged by investigator.

Hematology (Hemoglobin[hgb], hematocrit, erythrocytes[ery]:<0.8*lower limit of normal[LLN];reticulocytes, reticulocytes/ery:<0.5*LLN,>1.5*upper LN[ULN];ery mean corpuscular volume[EMC], EMC hgb:<0.9*LLN,>1.5*ULN;EMC hgb concentration:<0.9* LLN;platelet:<0.5*LLN;leukocytes[leu]:<0.6*LLN,>1.5*ULN;lymphocytes, lymphocytes/leu, neutrophils, neutrophils/leu:<0.8* LLN,>1.2*ULN;basophils, basophils/leu, eosinophils, eosinophils/leu, monocytes, monocytes/leu:>1.2*ULN;activated partial thromboplastin time[PTT], PTT, prothrombin time:>1.1*ULN);Clinical chemistry (Total/direct/indirect bilirubin, glucose-fasting:>1.5*ULN; aspartate aminotransferase[AT], alanine AT:>3.0*ULN; protein, albumin, HDL cholesterol:<0.8*LLN;urea nitrogen, creatinine, triglyceride, cholesterol:>1.3*ULN;urate, LDL cholesterol:>1.2*ULN;potassium:<0.9*LLN,>1.1*ULN;calcium, bicarbonate:<0.9*LLN;creatine kinase:>2.0*ULN);Urinalysis (pH<4.5;glucose, protein, hgb, ketones, nitrite, leu esterase, granular/hyaline/WBCs casts:>1).