A Study for Patients With Active Rheumatoid Arthritis Despite Ongoing Methotrexate Therapy

ACR50 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis. An ACR50 Responder is defined as a participant with \>50% improvement from baseline in both tender and swollen joint counts and in at least 3 of the following 5 criteria: physician global assessment, participant global assessment, functional ability measure (Health Assessment Questionnaire-Disability Index which measures participants' perceived degree of difficulty when performing various daily activities), visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein.

Time frame: Up to week 24

Population: Intent-to-treat (ITT) population included all randomized participants who received any amount of blinded study drug and who had at least 1 post-baseline efficacy assessment, Last Observation Carried Forward (LOCF). Two participants were excluded due to Good Clinical Practice (GCP) issues.

Serum immunoglobulin measured by Immunoglobulin G (IgG), Immunoglobulin M (IgM), and Immunoglobulin A (IgA) levels.

Time frame: Baseline, up to 24 weeks

Population: Intent-to-treat (ITT) population included all randomized participants who received any amount of blinded study drug and who had at least 1 post-baseline efficacy assessment, Last Observation Carried Forward (LOCF). 2 participants were excluded due to Good Clinical Practice (GCP) issues.

The number of swollen joints was determined by examination of 28 joints which include: the 2 shoulders, the 2 elbows, the 2 wrists, the 10 metacarpophalangeal joints, the 2 interphalangeal joints of the thumb, the 8 proximal interphalangeal joints, and the 2 knees. Joints were classified as either swollen or not swollen. Swelling was defined as palpable fluctuating synovitis of the joint.

Time frame: Baseline, up to 24 weeks

Population: Intent-to-treat (ITT) population included all randomized participants who received any amount of blinded study drug and who had at least 1 post-baseline efficacy assessment, Last Observation Carried Forward (LOCF). 2 participants were excluded due to Good Clinical Practice (GCP) issues.

B-lymphocyte antigen CD20 or CD20 is an activated-glycosylated phosphoprotein expressed on the surface of all mature B-cells. Total B cell counts (CD20+CD3-) are represented by the number of cells per microliter (cells/µL). The reference range is 43 - 602 cells/µL.

Time frame: Baseline, up to 24 weeks

Population: Intent-to-treat (ITT) population included all randomized participants who received any amount of blinded study drug and who had at least 1 post-baseline efficacy assessment, Last Observation Carried Forward (LOCF). 2 participants were excluded due to Good Clinical Practice (GCP) issues.

DAS (modified to include the 28 joint count \[DAS28\]) consists of a composite score of the following variables: tender joint count (TJC28), swollen joint count (SJC28), C-reactive protein (CRP), and participant global assessment of his or her disease activity (participant global visual analog scale \[pt global VAS\]). The DAS28 is calculated by using the following formula: DAS28-CRP = 0.56\*sqrt(28TJC) + 0.28\*sqrt(28SJC) + 0.36\*ln(CRP+1) + 0.014\*pt global VAS + 0.96. Scores ranged from 1.0-9.4, where lower scores indicated less disease activity.

Time frame: Baseline, up to 24 weeks

Population: Intent-to-treat (ITT) population included all randomized participants who received any amount of blinded study drug and who had at least 1 post-baseline efficacy assessment, Last Observation Carried Forward (LOCF). 2 participants were excluded due to Good Clinical Practice (GCP) issues.

The FACIT Fatigue Scale is a brief participant-reported measure of fatigue and consists of 13 items. Scores range from 0 to 52, with higher scores indicating less fatigue.

Time frame: Baseline, up to 24 weeks

Population: Intent-to-treat (ITT) population included all randomized participants who received any amount of blinded study drug and who had at least 1 post-baseline efficacy assessment, Last Observation Carried Forward (LOCF). 2 participants were excluded due to Good Clinical Practice (GCP) issues.

Participant's assessment of physical function. Disability section of questionnaire scores participant's self-perception on degree of difficulty (0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, and 3 = unable to do) when dressing and grooming, arising, eating, walking, hygiene, reach, grip, and performing other daily activities. Scores for each of the functional areas were averaged to calculate the functional disability index. The HAQ-DI total score, which is the average of the nonmissing functional scores, ranges from 0 (no disability) to 3 (severe disability).

Time frame: Baseline, up to 24 weeks

Population: Intent-to-treat (ITT) population included all randomized participants who received any amount of blinded study drug and who had at least 1 post-baseline efficacy assessment, Last Observation Carried Forward (LOCF). 2 participants were excluded due to Good Clinical Practice (GCP) issues.

Participant's assessment of disease activity using a visual analog scale (VAS), which ranged from 0 to 100 mm, where 0 indicated no arthritis activity and 100 indicated extremely active arthritis.

Time frame: Baseline, up to 24 weeks

Population: Intent-to-treat (ITT) population included all randomized participants who received any amount of blinded study drug and who had at least 1 post-baseline efficacy assessment, Last Observation Carried Forward (LOCF). 2 participants were excluded due to Good Clinical Practice (GCP) issues.

Participant's assessment of joint pain using a visual analog scale (VAS), which ranged from 0 to 100 mm, where 0 indicated no pain and 100 indicated worst possible pain.

Time frame: Baseline, up to 24 weeks

Population: Intent-to-treat (ITT) population included all randomized participants who received any amount of blinded study drug and who had at least 1 post-baseline efficacy assessment, Last Observation Carried Forward (LOCF). 2 participants were excluded due to Good Clinical Practice (GCP) issues.

Physician's assessment of disease activity using a visual analog scale (VAS) that ranged from 0 to 100 mm, where 0 indicated no arthritis activity and 100 indicated extremely active arthritis.

Time frame: Baseline, up to 24 weeks

Population: Intent-to-treat (ITT) population included all randomized participants who received any amount of blinded study drug and who had at least 1 post-baseline efficacy assessment, Last Observation Carried Forward (LOCF). 2 participants were excluded due to Good Clinical Practice (GCP) issues.

A self-reported questionnaire that consists of 36 questions covering 8 health domains (physical functioning, social functioning, bodily pain, vitality, mental health, role-physical, role-emotional, and general health). Each domain is scored by summing the individual items and transforming the scores into a 0 to 100 scale, with higher scores indicating better health status or functioning. The mental component summary (MCS) and the physical component summary (PCS) have been constructed based on the 8 SF-36 domains. MCS and PCS scores = 0 to 100 (higher scores indicate better health status).

Time frame: Baseline, up to 24 weeks

Population: Intent-to-treat (ITT) population included all randomized participants who received any amount of blinded study drug and who had at least 1 post-baseline efficacy assessment, Last Observation Carried Forward (LOCF). 2 participants were excluded due to Good Clinical Practice (GCP) issues.

Number of tender and painful joints was determined by examination of 28 joints (14 on each side) which include: the 2 shoulders, the 2 elbows, the 2 wrists, the 10 metacarpophalangeal joints, the 2 interphalangeal joints of the thumb, the 8 proximal interphalangeal joints, and the 2 knees. Joints were assessed by pressure and joint manipulation on physical examination. Participant was asked for pain sensations on these manipulations and watched for spontaneous pain reactions. Any positive response on pressure, movement, or both is translated into a single tender-versus-nontender dichotomy.

Time frame: Baseline, up to 24 weeks

Population: Intent-to-treat (ITT) population included all randomized participants who received any amount of blinded study drug and who had at least 1 post-baseline efficacy assessment, Last Observation Carried Forward (LOCF). 2 participants were excluded due to Good Clinical Practice (GCP) issues.

Serious adverse events and other nonserious adverse events are located in the Reported Adverse Event section.

Time frame: Baseline up to 24 weeks

Population: All randomized participants who received any amount of blinded study drug.

ACR20 Responder Index is composite of clinical, laboratory, and functional measures in rheumatoid arthritis. An ACR20 Responder is defined as participant with at least 20% improvement from baseline in both tender and swollen joint counts and in at least 3 of the following 5 criteria: physician global assessment, participant global assessment, functional ability measure (Health Assessment Questionnaire-Disability Index which measures participants' perceived degree of difficulty when performing various daily activities), visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein.

Time frame: Up to 24 weeks

Population: Intent-to-treat (ITT) population included all randomized participants who received any amount of blinded study drug and who had at least 1 post-baseline efficacy assessment, Last Observation Carried Forward (LOCF)/non-responder imputation (NRI). 2 participants were excluded due to Good Clinical Practice (GCP) issues.

The EULAR28 categorizes clinical response based upon improvement since baseline in the Disease Activity Score (DAS) modified to include the 28 joint count (DAS28) and post-baseline DAS28 level. DAS28 consists of a composite score of the following variables: tender joint count (TJC28), swollen joint count (SJC28), C-reactive protein (CRP), and participant global assessment of their disease activity (participant global visual analog scale \[VAS\]). EULAR28 categories include: No Response (improvement in DAS28 of less than or equal to 0.6 units or post-baseline DAS28 score greater than 5.1 with improvement by less than or equal to 1.2 units), Moderate Response (post-baseline DAS28 score less than or equal to 5.1 with improvement by more than 0.6 units but no greater than 1.2 units or post-baseline DAS28 score greater than 3.2 with improvement by more than 1.2 units), and Good Response (post-baseline DAS28 score less than or equal to 3.2 with improvement by more than 1.2 units).

Time frame: Up to 24 weeks

Population: Intent-to-treat (ITT) population included all randomized participants who received any amount of blinded study drug and who had at least 1 post-baseline efficacy assessment, Last Observation Carried Forward (LOCF). 2 participants were excluded due to Good Clinical Practice (GCP) issues.

Percent change = \[(postbaseline CRP - baseline CRP)/baseline CRP\]\*100.

Time frame: Baseline, up to 24 weeks

Population: Intent-to-treat (ITT) population included all randomized participants who received any amount of blinded study drug and who had at least 1 post-baseline efficacy assessment, Last Observation Carried Forward (LOCF). 2 participants were excluded due to Good Clinical Practice (GCP) issues.

C-trough is defined as the concentration of LY2127399 at the end of the dosing interval after the subcutaneous (sc) injection dosing once every 4 weeks. Mean C-trough value was obtained by conducting a simulation consisting of 1000 participants. The model was then used to predict the concentration-time profile at steady state. The pharmacokinetic (PK) parameters were then estimated from these concentration-time profiles.

Time frame: 24 weeks

Population: The PK analysis population included all intent-to-treat (ITT) participants who received LY2127399 and who had evaluable PK data except 2 participants who were excluded due to Good Clinical Practice (GCP) issues.

T1/2,tau is defined as the apparent steady state elimination within the dosing interval. T1/2,tau was obtained by conducting a simulation consisting of 1000 participants. The model was then used to predict the concentration-time profile at steady state. The pharmacokinetic (PK) parameters were then estimated from these concentration-time profiles.

Time frame: 24 weeks

Population: The PK analysis population included all intent-to-treat (ITT) participants who received LY2127399 and who had evaluable PK data except 2 participants who were excluded due to Good Clinical Practice (GCP) issues.