Phase IIb Study of IFN-K in Systemic Lupus Erythematosus

SLE Responder Index (SRI); SRI-4 responder was defined as a subject who had the following criteria at week 36:

• reduction ≥4 points in SELENA-SLEDAI at week 36 compared with baseline, and
• no new BILAG A at week 36, and
• no more than 1 new BILAG B at week 36, and
• no deterioration in PGA (<10% worsening) on 100-mm VAS compared with baseline

Lupus low disease activity state (LLDAS) was conceptually defined as 'a state which, if sustained, is associated with a low likelihood of adverse outcome, considering disease activity and medication safety'. Subsequently defined using consensus methodology, LLDAS is attained if all the following items are met:

• SLEDAI-2K ≤4, with no activity in major organ systems (renal, central nervous system (CNS), cardiopulmonary, vasculitis, fever) and no hemolytic anemia or gastrointestinal activity
• No new features of lupus disease activity compared with the previous assessment
• SELENA-SLEDAI physician global assessment (PGA, scale 0-3) ≤1
• Current prednisolone (or equivalent) dose ≤7.5 mg daily
• Well tolerated standard maintenance doses of immunosuppressive drugs and approved biological agents, excluding investigational drugs

British Isles Lupus Assessment Group (BILAG)-2004 index, it categorizes disease activity into 5 different levels from A to E, with Grade A representing very active disease and Grade E indicating no current or previous disease activity. Scoring was based on a total of 101 items, grouped into 9 organ/systems and the summation of the numerical values for the nine-system scores was given by the following formula: Numerical global score = A*12 + B*8 + C*1, where A, B and C represent the number of Grades A, B and C respectively at each assessment. Grades D and E are considered as 0 (Chee-Seng Yee et al, 2010). The minimum score is 0 with no predefined maximum. The higher scores mean a worse outcome.

The BILAG global score change from baseline to Last Available Value (LVA) week 24 and week 36 were presented analyzed.

Safety of Estrogens in Systemic Lupus Erythematosus National Assessment (SELENA)-SLEDAI, is a slightly modified version of the SLEDAI. This is a weighted index in which signs and symptoms, laboratory tests, and Physician's Global Assessment (PGA) for each of nine organ systems are given a weighted score and summed up if present at the time of the visit or in the preceding 10 days. The maximum theoretical score for the SELENA SLEDAI is 105 (all 24 descriptors present simultaneously) with 0 indicating inactive disease.

Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index for systemic lupus erythematosus (SLICC/ACR-DI) captures permanent changes which have occurred in patients with SLE, regardless of causality. The questionnaire contains 41 items covering 12 different organ systems. The score of items ranges from 1 to 3 and the total score from 0 to 47. By definition score 0 corresponds to diagnostics and damage over time can only be stable or increase, theoretically to a maximum of 47 points.

Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) was specifically developed to assess the cutaneous manifestations of SLE. It measures both disease activity and permanent damage (e.g. dyspigmentation and scarring) over the entire body surface. CLASI total activity score ranges from 0 to 70, with higher scores indicating more severe skin disease.

SRI (4) plus CS ≤ 7.5 mg/day responder was defined as a participant who had the following criteria at week 36:

• reduction ≥4 points in SELENA-SLEDAI at week 36 compared with baseline, and
• no new BILAG A at week 36, and
• no more than 1 new BILAG B at week 36, and
• no deterioration in PGA (<10% worsening) on 100-mm VAS compared with baseline plus CS ≤7.5mg equivalent prednisolone per day at week 36

SRI-4 plus CS ≤ 5mg/day responder was defined as a participant who had the following criteria at Week 36:

• reduction ≥4 points in SELENA-SLEDAI at week 36 compared with baseline, and
• no new BILAG A at week 36, and
• no more than 1 new BILAG B at week 36, and
• no deterioration in PGA (<10% worsening) on 100-mm VAS compared with baseline plus corticosteroids (CS) ≤5mg equivalent prednisolone per day at week 36

Individual serum antibody neutralizing capacity against recombinant IFN-alpha2b was measured by reporter gene assay using Interferon Sensitive Response Element (ISRE) reporter.

Number of participants who reported any treatment-related adverse events until month 9