Canakinumab for Treatment of Adult-onset Still's Disease

Responders included participants with change in disease activity score based on 28 joint counts and ESR (DAS28) score \> 1.2. The DAS28 score index is a composite score of weighted components including tender joint counts of 28, swollen joint counts of 28, patient global assessment of disease activity score, and the erythrocyte sedimentation rate (ESR) value. Total score ranged between 0-10. A DAS28-ESR score of 5.1 or above = high disease activity, a value between 3.2 and 5.1 = moderate disease activity and value between 2.6 and 3.2 = low disease activity, value \< 2.6 = disease remission.

Time frame: Week 12

Population: Intention-to-treat (ITT) population included all participants who did not violate any of the following inclusion criteria: diagnosis of adult-onset Still's disease and disease activity based on DAS28 score of ≥ 3.2 at Screening.

The 66 SJC included the 8 distal interphalangeal (IP), 10 proximal IP and 10 metacarpophalangeal (MTP) joints of hands, the 10 MTP and 10 proximal IP joints of feet, the 2 wrists, 2 elbows, 2 shoulders, 2 acromioclavicular, 2 sternoclavicular, 2 temporomandibular, 2 knee, 2 talo-tibial, and 2 mid-tarsal joints. Swelling was graded present (1) or absent (0). Total score is calculated by adding the scores, which range from 0 (no swollen joint) to 66 (all swollen joints). Lower scores indicate no swollen joint and higher scores indicate worsening swollen joints. A negative change in Baseline indicates improvement. LS mean was calculated by MMRM analyses.

Time frame: Baseline, Weeks 4, 8 and 12

Population: ITT population included all participants who did not violate any of the following inclusion criteria: diagnosis of adult-onset Still's disease and disease activity based on DAS28 score of ≥ 3.2 at Screening. Number analyzed is the number of participants with data available for analyses at the given timepoint.

A negative change from Baseline in CRP level indicates an improvement. LS mean was calculated by MMRM analyses.

Time frame: Baseline, Weeks 4, 8 and 12

Population: ITT population included all participants who did not violate any of the following inclusion criteria: diagnosis of adult-onset Still's disease and disease activity based on DAS28 score of ≥ 3.2 at Screening. Number analyzed is the number of participants with data available for analyses at the given timepoint.

A negative change from Baseline in ESR level indicates an improvement. LS mean was calculated by MMRM analyses.

Time frame: Baseline, Weeks 4, 8 and 12

Population: ITT population included all participants who did not violate any of the following inclusion criteria: diagnosis of adult-onset Still's disease and disease activity based on DAS28 score of ≥ 3.2 at Screening. Number analyzed is the number of participants with data available for analyses at the given timepoint.

The participant's global assessment of disease activity was assessed using a numerical rating scale of 0-10, where 0= no disease activity and 10= maximal disease activity. A negative change from Baseline indicates improvement. LS mean was calculated by MMRM analyses.

Time frame: Baseline, Weeks 4, 8 and 12

Population: ITT population included all participants who did not violate any of the following inclusion criteria: diagnosis of adult-onset Still's disease and disease activity based on DAS28 score of ≥ 3.2 at Screening. Number analyzed is the number of participants with data available for analyses at the given timepoint.

The participant's global assessment of pain was assessed using a numerical rating scale of 0-10, where 0= no disease activity and 10= maximal disease activity. A negative change from Baseline indicates improvement. LS mean was calculated by MMRM analyses.

Time frame: Baseline, Weeks 4, 8 and 12

Population: ITT population included all participants who did not violate any of the following inclusion criteria: diagnosis of adult-onset Still's disease and disease activity based on DAS28 score of ≥ 3.2 at Screening. Number analyzed is the number of participants with data available for analyses at the given timepoint.

The physician's global assessment of disease activity was assessed using a numerical rating scale of 0-10 where 0= no disease activity and 10= activity to maximal disease activity. A negative change from Baseline indicates improvement. LS mean was calculated by MMRM analyses.

Time frame: Baseline, Weeks 4, 8 and 12

Population: ITT population included all participants who did not violate any of the following inclusion criteria: diagnosis of adult-onset Still's disease and disease activity based on DAS28 score of ≥ 3.2 at Screening. Number analyzed is the number of participants with data available for analyses at the given timepoint.

The 68 TJC included the 8 distal interphalangeal (IP), 10 proximal IP and 10 metacarpophalangeal (MTP) joints of hands, the 10 MTP and 10 proximal IP joints of feet, the 2 wrists, 2 elbows, 2 shoulders, 2 acromioclavicular, 2 sternoclavicular, 2 temporomandibular, 2 hip, 2 knee, 2 talo-tibial, and 2 mid-tarsal joints. Joint tenderness was graded present (1) or absent (0). Total score is calculated by adding the scores, which range from 0 (no tender joint) to 68 (all tender joints). Lower scores indicate no tender joint and higher scores indicate worsening tender joints. A negative change from Baseline indicates improvement. LS mean was calculated by MMRM analyses.

Time frame: Baseline, Weeks 4, 8 and 12

Population: ITT population included all participants who did not violate any of the following inclusion criteria: diagnosis of adult-onset Still's disease and disease activity based on DAS28 score of ≥ 3.2 at Screening. Number analyzed is the number of participants with data available for analyses at the given timepoint.

The DAS28 index is a composite score of weighted components including tender joint counts of 28, swollen joint counts of 28, patient global assessment of disease activity score, and CRP value. Total score ranged between 0-10. A DAS28-CRP score of 5.1 or above = high disease activity, a value between 3.2 and 5.1 = moderate disease activity and value between 2.6 and 3.2 = low disease activity, value \< 2.6 = disease remission. A positive change in score indicates worsening, and a negative change indicates improvement. LS mean was calculated by MMRM analyses.

Time frame: Baseline, Weeks 4, 8 and 12

Population: ITT population included all participants who did not violate any of the following inclusion criteria: diagnosis of adult-onset Still's disease and disease activity based on DAS28 score of ≥ 3.2 at Screening. Number analyzed is the number of participants with data available for analyses at the given timepoint.

The HAQ measures physical disability and functional status. It has 4 dimensions: disability, pain, drug side effects and dollar costs. The HAQ score is calculated by summing the computed scores for each category and dividing by the number of categories answered. It ranges from 0 (without any difficulty) to 3 (unable to do). A negative change from Baseline indicates improvement. LS mean was calculated by MMRM analyses.

Time frame: Baseline, Week 12

Population: ITT population included all participants who did not violate any of the following inclusion criteria: diagnosis of adult-onset Still's disease and disease activity based on DAS28 score of ≥ 3.2 at Screening. Number analyzed is the number of participants with data available for analyses at the given timepoint.

The SF-36 determines overall quality of life assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 contribute to physical component summary score (PCS). Items 5-8 contribute to mental component summary score (MCS). Scores on each item are summed and averaged (range = 0 worst-100 best). Positive numbers indicate improvement from Baseline. LS mean was calculated by MMRM analyses.

Time frame: Baseline, Week 12

Population: ITT population included all participants who did not violate any of the following inclusion criteria: diagnosis of adult-onset Still's disease and disease activity based on DAS28 score of ≥ 3.2 at Screening. Number analyzed is the number of participants with data available for analyses at the given timepoint.

LS mean was calculated by MMRM analyses.

Time frame: Week 12

Population: ITT population included all participants who did not violate any of the following inclusion criteria: diagnosis of adult-onset Still's disease and disease activity based on DAS28 score of ≥ 3.2 at Screening. Number analyzed is the number of participants with data available for analyses at the given timepoint.

A total of 28 joints were assessed for swelling. The number of swollen joints could range from 0 to 28, where higher values represented more swollen joints. The change from Baseline to any time point was averaged among all participants, where negative changes indicated an improvement in disease activity. LS mean was calculated by MMRM analyses.

Time frame: Baseline, Weeks 4, 8 and 12

Population: ITT population included all participants who did not violate any of the following inclusion criteria: diagnosis of adult-onset Still's disease and disease activity based on DAS28 score of ≥ 3.2 at Screening. Number analyzed is the number of participants with data available for analyses at the given timepoint.

A total of 28 joints were assessed for tenderness. The number of tender joints could range from 0 to 28, where higher values represented more tender joints. The change from Baseline to any time points was averaged among all participants, where negative changes indicated an improvement in disease activity. LS mean was calculated by MMRM analyses.

Time frame: Baseline, Weeks 4, 8 and 12

Population: ITT population included all participants who did not violate any of the following inclusion criteria: diagnosis of adult-onset Still's disease and disease activity based on DAS28 score of ≥ 3.2 at Screening. Number analyzed is the number of participants with data available for analyses at the given timepoint.

The DAS28 index is a composite score of weighted components including tender joint counts of 28, swollen joint counts of 28, patient global assessment of disease activity score, and ESR value.Total score ranged between 0-10. A DAS28-ESR score of 5.1 or above = high disease activity, a value between 3.2 and 5.1 = moderate disease activity and value between 2.6 and 3.2 = low disease activity, value \< 2.6 = disease remission. A positive change in score indicates worsening, and a negative change indicates improvement. Least squares (LS) mean was calculated by mixed linear model for repeated measures (MMRM) analyses.

Time frame: Baseline, Weeks 4, 8 and 12

Population: ITT population included all participants who did not violate any of the following inclusion criteria: diagnosis of adult-onset Still's disease and disease activity based on DAS28 score of ≥ 3.2 at Screening. Number analyzed is the number of participants with data available for analyses at the given timepoint.

Number of joints with limitation of motion according to neutral zero method was assessed which included mobility of joints (elbows, wrists, shoulder joints, hip joints, knee joints, and upper ankle joints) within the reference range/degree. Response is defined as an improvement of ≥ 30%, 50%, 70% and 90% from Baseline. A negative change score indicates improvement. LS mean was calculated by MMRM analyses.

Time frame: Baseline, Week 12

Population: ITT population included all participants who did not violate any of the following inclusion criteria: diagnosis of adult-onset Still's disease and disease activity based on DAS28 score of ≥ 3.2 at Screening. Number analyzed is the number of participants with data available for analyses at the given timepoint.

Participants with disease remission: LDA (DAS28 score\< 2.6). The DAS28 index is a composite score of weighted components including both 28 TJC an SJC, participant global assessment of disease activity score, and ESR or CRP value. A DAS28 score greater than 5.1: high disease activity, ≤ 3.2: low disease activity, and less than 2.6: remission. Extended remission criteria included DAS28 \< 2.6 and no signs of systemic activity for up to two consecutive study visits till Week 12 defined as any of Yamaguchi´s primary classification criteria for AOSD which included fever attacks at 39 °C for more than a week, arthralgia, salmon red, maculate, urticarial or maculo-papular rash and leukocytosis (white blood cells increase) of \> 10000/cubic millimeters (mm\^3) with \> 80% neutrophils.

Time frame: Week 12

Population: ITT population included all participants who did not violate any of the following inclusion criteria: diagnosis of adult-onset Still's disease and disease activity based on DAS28 score of ≥ 3.2 at Screening.

Percentage of responders were defined as the participants who achieved LDA (DAS28 score \< 3.2) at Week 12. The DAS28 index is a composite score of weighted components including tender joint counts of 28, swollen joint counts of 28, participant global assessment of disease activity score, and ESR or CRP value. Total score ranged between 0-10. A DAS28 score greater than 5.1 implies high disease activity, equal to or less than 3.2 low disease activity, and less than 2.6 remissions.

Time frame: Week 12

Population: ITT population included all participants who did not violate any of the following inclusion criteria: diagnosis of adult-onset Still's disease and disease activity based on DAS28 score of ≥ 3.2 at Screening.

ACR30 response was defined as a ≥ 30% improvement (reduction) compared with Baseline for both 68 TJC and 66 SJC, as well as for three of the additional five ACR core set variables: Participant's Assessment of Pain over the previous 24 hours: using a NRS left end of the line 0=no pain to right end of the line 10=unbearable pain; Participant's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a NRS where left end of the line 0=no disease activity to right end of the line 10=maximum disease activity; HAQ 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant ESR.

Time frame: Baseline, Week 12

Population: ITT population included all participants who did not violate any of the following inclusion criteria: diagnosis of adult-onset Still's disease and disease activity based on DAS28 score of ≥ 3.2 at Screening.

ACR50 response was defined as a ≥ 50% improvement (reduction) compared with Baseline for both 68 TJC and 66 SJC, as well as for three of the additional five ACR core set variables: Participant's Assessment of Pain over the previous 24 hours: using a NRS left end of the line 0=no pain to right end of the line 10=unbearable pain; Participant's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a NRS where left end of the line 0=no disease activity to right end of the line 10=maximum disease activity; HAQ-DI 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant ESR.

Time frame: Baseline, Week 12

Population: ITT population included all participants who did not violate any of the following inclusion criteria: diagnosis of adult-onset Still's disease and disease activity based on DAS28 score of ≥ 3.2 at Screening.

ACR70 response was defined as a ≥ 70% improvement (reduction) compared with Baseline for both 68 TJC and 66 SJC, as well as for three of the additional five ACR core set variables: Participant's Assessment of Pain over the previous 24 hours: using a NRS left end of the line 0=no pain to right end of the line 10=unbearable pain; Participant's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a NRS where left end of the line 0=no disease activity to right end of the line 10=maximum disease activity; HAQ-DI 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant ESR.

Time frame: Baseline, Week 12

Population: ITT population included all participants who did not violate any of the following inclusion criteria: diagnosis of adult-onset Still's disease and disease activity based on DAS28 score of ≥ 3.2 at Screening.

ACR90 response was defined as a ≥ 90% improvement (reduction) compared with Baseline for both 68 TJC and 66 SJC, as well as for three of the additional five ACR core set variables: Participant's Assessment of Pain over the previous 24 hours: using a NRS left end of the line 0=no pain to right end of the line 10=unbearable pain; Participant's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a NRS where left end of the line 0=no disease activity to right end of the line 10=maximum disease activity; HAQ-DI 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant ESR.

Time frame: Baseline, Week 12

Population: ITT population included all participants who did not violate any of the following inclusion criteria: diagnosis of adult-onset Still's disease and disease activity based on DAS28 score of ≥ 3.2 at Screening.

ACR20 response was defined as a ≥ 20% improvement (reduction) compared with Baseline for both 68 TJC and 66 SJC, as well as for three of the additional five ACR core set variables: Participant's Assessment of Pain over the previous 24 hours: using a NRS left end of the line 0=no pain to right end of the line 10=unbearable pain; Participant's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a NRS where left end of the line 0=no disease activity to right end of the line 10=maximum disease activity; HAQ-DI 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant ESR.

Time frame: Baseline, Week 12

Population: ITT population included all participants who did not violate any of the following inclusion criteria: diagnosis of adult-onset Still's disease and disease activity based on DAS28 score of ≥ 3.2 at Screening.

EULAR response is based on DAS28-ESR and DAS28-CRP scores. The DAS28 index is a composite score of weighted components including tender joint counts of 28, swollen joint counts of 28, subject global assessment of disease activity score, and ESR or CRP value. A DAS28-CRP or ESR score of 5.1 or above = high disease activity, a value between 3.2 and 5.1 = moderate disease activity and value between 2.6 and 3.2 = low disease activity, value \< 2.6 = disease remission. EULAR response has 3 categories: EULAR Good response: DAS28 ≤ 3.2 and a change from Baseline \< -1.2. EULAR Moderate response: DAS28 \>3.2 to ≤ 5.1 or a change from Baseline \< -0.6 to ≥ -1.2 or EULAR No response: DAS28 \>5.1 or a change from Baseline \< -0.6 to ≤ -1.2.

Time frame: Baseline, Week 12

Population: ITT population included all participants who did not violate any of the following inclusion criteria: diagnosis of adult-onset Still's disease and disease activity based on DAS28 score of ≥ 3.2 at Screening.

Fever is defined as an oral or rectal body temperature greater than 38 degrees Celsius (°C).

Time frame: Week 12

Population: ITT population included all participants who did not violate any of the following inclusion criteria: diagnosis of adult-onset Still's disease and disease activity based on DAS28 score of ≥ 3.2 at Screening.

A participant was considered responder if he/she had achieved the incidence of modified adapted response (ACR30 criteria) of at least a 30% improvement in no intermittent fever and had at least 30% improvement in at least 6 of the following 7 measures: tender and swollen 68-joint counts, participant's assessment of pain, participant's global assessment of disease activity, physician's global assessment of disease activity, participant's functional capacity (HAQ-DI score) and acute phase reactant- ESR. Participant were modified ACR30 responders at a given post-randomization visit if they satisfied the modified ACR30 criteria, respectively.

Time frame: Baseline, Week 12

Population: ITT population included all participants who did not violate any of the following inclusion criteria: diagnosis of adult-onset Still's disease and disease activity based on DAS28 score of ≥ 3.2 at Screening.

An AE is an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. AEs include symptoms of illnesses, as well as every unfavourable and unintended reaction. SAEs are AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.

Time frame: Up to Month 27

Population: Safety Analysis Set included all participants randomized who received at least one dose of the study drug.