Long-term Assessment of Safety and Efficacy of BI 695501 in Patients With Rheumatoid Arthritis

The analysis of AEs was based on the concept of treatment-emergent AEs (TEAEs). Thus, all AEs with an onset after the first dose of trial drug up to a period of ten weeks after the last dose of trial drug were assigned to the current treatment for evaluation. Investigator assessed drug related AEs were AEs with a relationship to drug ticked yes according to the Investigator.

Time frame: From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks.

Population: Safety Analysis Set (SAF): All patients who received at least 1 dose during trial 1297.3. In the event of doubt as to whether a patient was treated or not, they were assumed to have been treated for the purposes of analysis, and thus included in the SAF. Patients were classified according to randomized/re-randomized treatments of Trial 1297.2.

The DAS28 (ESR) score was derived using the following formulae: DAS28 (ESR) = 0.56\*√(TJC28) + 0.28\*√(SJC28) + 0.014\*(GH) + 0.7\*ln(ESR) Where: • TJC28 = 28 joint count for tenderness • SJC28 = 28 joint count for swelling • GH = General Health component of the DAS (patient's global assessment of disease activity) • Ln (ESR) = natural logarithm of ESR. Last observation carried forward (LOCF) is the method used for handling missing components post baseline. Baseline for this trial was taken from the baseline of 1297.2. Improvement in DAS28 was also categorized using the European League Against Rheumatism (EULAR) response criteria. The DAS28 provides a number on a scale from 0 to 10 where higher values mean a higher disease activity. A DAS28 above 5.1 means high disease activity whereas a DAS28 below 3.2 indicates low disease activity. Remission is achieved by a DAS28 lower than 2.6.

Time frame: Baseline and Week 48.

Population: FullAnalysisSet(FAS) includes patients from the all subjects assigned set who received at least 1 dose of trial drug in Trial 1297.3 and had at least 1 DAS28(ESR and C-reactive protein) or american college of rheumatology 20% response criteria (ACR20) measured during trial. Classified according to randomized/rerandomized treatments of trial 1297.2.

The proportion of patients meeting the ACR20 response criteria was assessed. A patient had an ACR20 response if all of the following occurred: A ≥ 20 % improvement in the swollen joint count (66 joints), A ≥ 20 % improvement in the tender joint count (68 joints), A ≥ 20 % improvement in at least three of the following assessments: Patient's assessment of pain, Patient's global assessment of disease activity (equivalent to the General Health component of the Disease Activity Score (\[DAS\]), Physician's global assessment of disease activity, Patient's assessment of physical function, as measured by the Health Assessment Questionnaire - Disability Index (HAQ-DI) Acute phase reactant (C-reactive protein \[CRP\]).

Time frame: Week 48.

Population: FAS, All patients who discontinue treatment, are lost-to-follow-up or have any severe violation related to any therapy that may significantly impact efficacy assessment prior to the secondary endpoint assessment will be considered as a non-responder (NRI).

The ACR/EULAR remission criteria were based on a Boolean definition. At any time point, the patient must have satisfied all of the following: * Tender joint count (TJC) ≤ 1 * Swollen joint count (SJC) ≤ 1 * C-reactive protein (CRP) ≤ 1 mg/dL * Patient global assessment of disease activity ≤ 10 (on a 0 to 100 scale) For TJC and SJC, use of a 28-joint count may have missed actively involved joints, particularly in the feet and ankles. It was preferable to include the feet and ankles when evaluating remission.

Time frame: Week 48.

Population: FAS

Percentage of patients with European League Against Rheumatism (EULAR) response (good response, moderate response, or no response) were calculated at Week 48 for assessment of this outcome measure. No response: If improvement in DAS28 (ESR) at w48 \<=0.6, or if DAS28(ESR) at w48 \>5.1 and improvement is in range \>0.6 to \<1.2. Moderate response: If DAS28(ESR) at w48 \<=5.1 and improvement is in range \>0.6 to \<1.2, or, DAS28(ESR) at w48 \>3.2 and improvement is in range \>=1.2. Good response: If DAS28(ESR) at w48 \<=3.2 and improvement \>=1.2.

Time frame: Week 48.

Population: FAS