Trial Outcomes & Findings for A Multi-Site Study to Evaluate the Safety and Effect of Study Drug on Participants With Rheumatoid Arthritis (NCT NCT00308282)

Study populations are based on randomized treatment groups. Safety and Pharmacokinetic (PK) populations were adjusted due to dosing errors and account for actual treatment received.

Completers were defined as having completed 3 infusions and required follow-up visits.

A Multi-Site Study to Evaluate the Safety and Effect of Study Drug on Participants With Rheumatoid Arthritis

ACR Responder Index is a Composite of clinical, laboratory, and functional measures of rheumatoid arthritis (RA). ACR20 Responders: had ≥20% improvement from baseline in both tender and swollen joint counts and ≥20% improvement in at least 3 of 5 criteria: participant's and physician's global assessment of disease activity, Health Assessment Questionnaire-Disability Index (HAQ-DI) (which measured participants' perceived degree of difficulty performing daily activities), visual analog pain scale, and erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP).

Treatment-emergent adverse events (TEAEs) were defined as those AEs with start date and time equal to or after the start of study medication infusion. In the case of a missing onset time for an AE, an AE with a start date equal to or greater than the dosing date was considered treatment-emergent. A summary of other nonserious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section. All participants who received at least one dose of study drug. Due to dosing errors (a participant received 60 mg LY2127399 in the placebo group), the safety population was adjusted to account for actual treatment received.

Population estimate of constant clearance as determined by population PK analysis. A 2-compartment model was used in PK modeling. Constant clearance is the PK parameter which describes the linear elimination of LY2127399 from serum.

ACR Responder Index: composite of clinical, laboratory, and functional measures of Rheumatoid Arthritis (RA). ACR50 and ACR70 Responder: had either a ≥50% or ≥70% improvement from baseline in both tender and swollen joint counts and either a ≥50% or ≥70% improvement in at least 3 of 5 criteria: participant's (Pt's) and physician's global assessment of disease activity, HAQ-DI (measured Pts' perceived degree of difficulty performing daily activities), joint pain, and CRP (respectively).

Disease Activity Score (DAS) modified to include 28 joint count (DAS28) consisted of composite score of following variables: tender joint count (TJC28), swollen joint count (SJC28), CRP \[milligrams per liter (mg/L)\], and participant's global assessment of disease activity using visual analog scale (VAS) (participant global VAS). DAS28-CRP=0.56\*square root (sqrt)(TJC28)+0.28\*sqrt(SJC28)+0.36\*natural log(CRP+1)+0.014\*participant global VAS+0.96. Scores ranged from 1.0-9.4, where lower scores indicated less disease activity and remission is DAS28-CRP \<2.6. A negative change indicated an improvement.

EULAR Responder index based on 28 joint counts categorizes clinical response based on improvement since baseline in DAS28-CRP. DAS28-CRP scores range from 1.0-9.4, where lower scores indicated less disease activity. High disease activity: DAS28-CRP \>5.1, low disease activity: DAS28-CRP \<3.2, and remission: DAS28-CRP \<2.6. Participants are categorized as EULAR responders or non-responders (NR) based on improvement of DAS28-CRP scores from baseline. EULAR DAS28-CRP responder index defines a good (absolute: \<3.2 or \>1.2 improvement from baseline), moderate (absolute: 3.2-5.1 or 0.6-1.2 improvement from baseline), or no response (absolute: \>5.1 or \<0.6 improvement from baseline). Percentage of participants with DAS28-CRP based EULAR response =(number of participants with specific response) / (number of participants analyzed in the group) \* 100.

Immunoglobulins (Ig), or antibodies, are large proteins used by the immune system to identify and neutralize foreign particles such as bacteria and viruses. Their normal blood levels indicate proper immune status. A negative change indicates a decrease in Ig levels.

CD20+ B-cells are a disease-related peripheral blood biomarker used to assess disease progression of Rheumatoid Arthritis (RA). A reduction in CD20+ B-cell values may indicate an improvement in RA symptoms.