A Long-Term Study of the Safety and Tolerability of Repeated Administration of CEP-33457 in Participants With Systemic Lupus Erythematosus

An SRI response was defined as a reduction from baseline in SLE Disease Activity Index 2000 (SLEDAI-2K) score of ≥4 points, no worsening in Physician Global Assessment (PhGA), no new British Isles Lupus Assessment Group (BILAG) A body system score, and ≤1 new BILAG B body system score from baseline. SLEDAI 2K includes 24 weighted clinical and laboratory variables. Total score = 0 to 105. A score of 6 to 10 = moderate disease activity, and a reduction of >3 points = improvement. PhGA was completed by physician using a visual analog scale (VAS) from 0=none to 3=severe. A change of >0.3 points = worsening. BILAG includes 97 clinical and laboratory items. Each organ system is assigned a score displayed as a grade from A to E: A=very active disease; B=participant needs increase in treatment for moderately active disease; C=stable or mild disease; D=previous organ involvement but no current disease activity; and E=no current disease activity and organ system has never been involved.

The SLEDAI-2K is a validated objective measure that assesses disease activity within the last 28 days before completion of the index. It is a global index and includes 24 weighted clinical and laboratory variables. The total score (sum of all 24 scores) ranges from 0 to 105, with higher scores representing increased disease activity.

The BILAG-2004 is a validated objective and subjective global measure of the SLE disease activity, based on the physician's intention to treat, and refers to disease activity within the last 4 weeks before completion of the index. It includes 97 clinical and laboratory components to evaluate SLE disease activity in 9 different body systems (constitutional, mucocutaneous, neuropsychiatric, musculoskeletal, cardiorespiratory, gastrointestinal, ophthalmic, renal, and hematological). Each body system is assigned a score displayed as a grade from A to E, as follows: A=very active disease; B=participant needs increase in treatment for moderately active disease; C=stab1e or mild disease; D=previous system involvement but no current disease activity; and E=no current disease activity and the body system has never been involved. BILAG 2004 response was defined as no new BILAG A body system score and no more than 1 new BILAG B body system score from baseline.

The PhGA was completed by the physician using a 3-inch visual analog scale (VAS) labeled from 0=none to 3=severe. A change of greater than 0.3 point on the VAS indicates worsening. The number of participants showing no worsening are presented.

The PtGA was completed by the participant, using a 3-inch VAS labeled from 0=none to 3=severe. A change of greater than 0.3 point on the VAS indicated worsening. The number of participants showing no worsening are presented.

The SF-36 questionnaire has 36 questions composing the scale that represent 8 domains: 1) physical functioning, 2) physical role functioning, 3) bodily pain, 4) general health, 5) vitality, 6) social functioning, 7) emotional role functioning, and 8) mental health. All domains are scored on a scale from 0 (worst) to 100 (best), with higher scores representing the best possible health state. Change from baseline scores in the following individual standardized domains: Bodily pain, physical functioning, social functioning and vitality were presented.

Anti-UI RNP Ab was measured from blood serum collected at specified time points.

CRP was measured from blood serum samples at specified time points.

Anti-nuclear antibodies (ANA) were measured from blood serum samples at specified time points.

The SELENA Flare Index divides flares into 2 categories: mild/moderate and severe. A severe flare would lead to early withdrawal. The number of participants with mild to moderate flare, severe flare, and no flare at each visit during the treatment period were reported.

The SLICC/ACR damage index assesses specific comorbidities associated with SLE. It consists of 41 items and covers 12 body systems. Total damage scores were calculated using the 41 items. The total damage score ranges from 0 (no damage) to 47 (maximum disease damage severity) with higher scores indicating increasing disease damage severity.

Remission of disease was defined as a reduction of SLEDAI-2K score to 0. The SLEDAI-2K is a validated objective measure that assesses disease activity within the last 28 days before completion of the index. It is a global index and includes 24 weighted clinical and laboratory variables. The total score (sum of all 24 scores) ranges from 0 to 105, with higher scores representing increased disease activity.

Number of participants with change in steroid dose (prednisone equivalent/day) were reported. The change in steroid dose was evaluated to determine the number of participants taking a dose less than 7.5 mg of prednisone equivalent/day, a dose of 7.5 mg prednisone equivalent/day or more, and none per day.

Immunogenicity was assessed by detection of the presence of specific anti-CEP-33457 antibodies in blood serum samples collected at the specified time points.