Canakinumab for Treatment of Adult-onset Still's Disease (CONSIDER)

• ClinicalTrials.gov Identifier: NCT02204293
• Recruitment Status: Terminated
• First Posted: July 30, 2014
• Results First Posted: August 7, 2020
• Last Update Posted: August 7, 2020
• Sponsor: Charite University, Berlin, Germany
• Information provided by (Responsible Party): Eugen Feist, Charite University, Berlin, Germany

Study Description

Brief Summary:

The purpose of this trial is to investigate the efficacy of the treatment with canakinumab in participants with Adult-onset Still's Disease (AOSD) and active joint involvement.

Condition or disease	Intervention/treatment	Phase
Adult-Onset Still´s Disease	Drug: Canakinumab; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 36 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Study Protocol for a Multi-Centre, Placebo-Controlled Phase II Study of Canakinumab for the Treatment of Adult-onset Still's Disease (AOSD) Including an Open-label Long Term Extension
• Actual Study Start Date: June 21, 2012
• Actual Primary Completion Date: May 5, 2018
• Actual Study Completion Date: May 5, 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: Canakinumab; Participants received canakinumab 4 mg/kg up to a maximum of 300 mg subcutaneous (SC) injection, once in morning on Day 0, Weeks 4, 8, and 12 in Part I of the core study. Participants with response (change in DAS score > 1.2 at Week 12) continued to receive same dose of canakinumab in Part II for Weeks 12, 16, and 20. Participants who had remission (change in DAS score > 1.2 and no signs of systemic activity for adult-onset Still's disease at Week 20) entered Long-term extension (LTE) phase and received same dose of canakinumab at Weeks 24 and 28, which was down titrated to 2 mg/kg if applicable from Week 28 up to Month 27.	Drug: Canakinumab; Canakinumab, single-dose 4 mg/kg up to 300 mg administered subcutaneously.; Other Name: Ilaris
Placebo Comparator: Placebo; Participants received placebo, SC injection, once in morning on Day 0, Weeks 4, 8, and 12 in Part I of the core study. Participants with response (change in DAS score > 1.2 at Week 12) continued to receive placebo at Weeks 12, 16, and 20. Non-responders (who had change in DAS score ≤ 1.2) were unblinded to receive canakinumab 4 mg/kg (up to 300 mg maximum), SC injection, at Weeks 12, 16, and 20. Participants who had remission (change in DAS score > 1.2 and no signs of systemic activity for adult-onset Still's disease at Week 20) entered Long-term extension (LTE) phase and received same dose of canakinumab at Weeks 24 and 28, which was down titrated to 2 mg/kg if applicable from Week 28 up to Month 27.	Drug: Canakinumab; Canakinumab, single-dose 4 mg/kg up to 300 mg administered subcutaneously.; Other Name: Ilaris; Drug: Placebo; Matching placebo administered subcutaneously.

Outcome Measures

Primary Outcome Measures :

1. Core Study Part I: Percentage of Responders as Assessed by Disease Activity Score 28 Joints (DAS28) Score at Week 12 [ Time Frame: Week 12 ]
   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.

Secondary Outcome Measures :

1. Core Study Part I: Change From Baseline (CFB) in Disease Activity Score 28 Joints Erythrocyte Sedimentation Rate (DAS28 [ESR]) Score [ Time Frame: Baseline, Weeks 4, 8 and 12 ]
   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.
2. Core Study Part I: CFB in DAS28 C-reactive Protein (CRP) Score [ Time Frame: Baseline, Weeks 4, 8 and 12 ]
   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.
3. Core Study Part I: CFB in American College of Rheumatology (ACR) Component: 68 Tender Joint Count (TJC) [ Time Frame: Baseline, Weeks 4, 8 and 12 ]
   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.
4. Core Study Part I: CFB in ACR Component: 66 Swollen Joint Count (SJC) [ Time Frame: Baseline, Weeks 4, 8 and 12 ]
   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.
5. Core Study Part I: CFB in the 28 TJC [ Time Frame: Baseline, Weeks 4, 8 and 12 ]
   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.
6. Core Study Part I: CFB in the 28 SJC [ Time Frame: Baseline, Weeks 4, 8 and 12 ]
   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.
7. Core Study Part I: CFB in ACR Component: Acute Phase Reactant CRP [ Time Frame: Baseline, Weeks 4, 8 and 12 ]
   A negative change from Baseline in CRP level indicates an improvement. LS mean was calculated by MMRM analyses.
8. Core Study Part I: CFB in ACR Component: Acute Phase Reactant ESR [ Time Frame: Baseline, Weeks 4, 8 and 12 ]
   A negative change from Baseline in ESR level indicates an improvement. LS mean was calculated by MMRM analyses.
9. Core Study Part I: CFB in Serum Ferritin Level at Week 12 [ Time Frame: Week 12 ]
   LS mean was calculated by MMRM analyses.
10. Core Study Part I: Percentage of Responders With Fever Episodes [ Time Frame: Week 12 ]
    Fever is defined as an oral or rectal body temperature greater than 38 degrees Celsius (°C).
11. Core Study Part I: CFB in ACR Component: Physician's Global Assessment of Disease Activity Score [ Time Frame: Baseline, Weeks 4, 8 and 12 ]
    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.
12. Core Study Part I: CFB in ACR Component: Participant's Global Assessment of Disease Activity Score [ Time Frame: Baseline, Weeks 4, 8 and 12 ]
    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.
13. Core Study Part I: CFB in ACR Component: Participant's Global Assessment of Pain Score [ Time Frame: Baseline, Weeks 4, 8 and 12 ]
    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.
14. Core Study Part I: CFB in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score [ Time Frame: Baseline, Week 12 ]
    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.
15. Core Study Part I: Percentage of Responders With American College of Rheumatology Response of 20 (ACR20) [ Time Frame: Baseline, Week 12 ]
    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.
16. Core Study Part I: Percentage of Responders With ACR30 [ Time Frame: Baseline, Week 12 ]
    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.
17. Core Study Part I: Percentage of Responders With Modified ACR30 [ Time Frame: Baseline, Week 12 ]
    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.
18. Core Study Part I: Percentage of Responders With ACR50 [ Time Frame: Baseline, Week 12 ]
    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.
19. Core Study Part I: Percentage of Responders With ACR70 [ Time Frame: Baseline, Week 12 ]
    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.
20. Core Study Part I: Percentage of Responders With ACR90 [ Time Frame: Baseline, Week 12 ]
    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.
21. Core Study Part I: Percentage of Responders With European League Against Rheumatism (EULAR) Response [ Time Frame: Baseline, Week 12 ]
    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.
22. Core Study Part I: Percentage of Responders Achieving Low Disease Activity (LDA) [ Time Frame: Week 12 ]
    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.
23. Core Study Part I: Percentage of Responders Achieving Disease Remission and Extended Disease Remission [ Time Frame: Week 12 ]
    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.
24. Core Study Part I: Change in Joint Mobility (Degrees of Motion) Assessed by Neutral Zero Method [ Time Frame: Baseline, Week 12 ]
    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.
25. Core Study Part I: CFB in Medical Outcome Short Form (SF-36) Health Survey Score [ Time Frame: Baseline, Week 12 ]
    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.
26. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to Month 27 ]
    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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Written and signed consent from the participant to take part in the study
2. Men and women aged ≥ 18 years and ≤ 75 years
3. Fulfilment of AOSD classification criteria (according to Yamaguchi et al, J. Rheumatology, 1992)
4. Disease activity based on Disease Activity Score 28 (DAS28) of ≥3.2 at screening
5. At least 4 painful and 4 swollen joints at screening and baseline (of the 28 joints according to DAS28)
6. If undergoing treatment with non-steroidal anti-inflammatory drugs (NSAIDs), stable dose for at least 4 weeks prior to randomisation
7. If undergoing treatment with glucocorticoids, stable dose of ≤10 milligrams per day (mg/day) (prednisolone or equivalent) for at least 4 weeks prior to randomisation
8. If undergoing treatment with conventional disease-modifying anti-rheumatic drugs (DMARD), stable dose for at least 3 months prior to randomisation
9. Normalisation period for biological DMARDS (anakinra 1 week, etanercept 1 month, adalimumab and certolizumab 2 months, infliximab, golimumab, abatacept and tocilizumab 3 months, rituximab 9 months, canakinumab 6 months) prior to randomisation
10. In participants of reproductive age, use of an effective method of contraception as well as negative pregnancy test prior to the study commencing.

Exclusion Criteria:

1. Previous treatment with the study drug with repeated administration of canakinumab
2. Intraarticular or intravenous administration of glucocorticoids within 4 weeks prior to the baseline or use of narcotic analgesics except for analgesics permitted within the framework of the investigation (codeine and tramadol)
3. Presence of another, serious chronic-inflammatory disease
4. Positive hepatitis B antigen (HBsAg), hepatitis C antibodies and/or human immunodeficiency virus (HIV) antibodies.
5. Presence of a relevant, active infection or other diseases, which entail a tendency towards infection
6. Positive screening for latent tuberculosis, in accordance with usual local practice
7. Raised liver count (raised bilirubin; alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 3-fold the normal range)
8. Serum-creatinine concentration >1.5 milligrams per deciliter (mg/dL)
9. Inadequate haematological findings (hemoglobin [Hb] ≤ 10 grams per deciliter (g/dL), neutrophils ≤2,500/microliter (µl) and thrombocytes ≤100,000/µl)
10. Simultaneous participation in any other interventional clinical study within the last 30 days preceding the commencement of the study
11. History of neoplasia with the exception of a curatively treated non-melanoma skin tumour or carcinoma of the cervix treated in situ without any indication of recurrence within the last 10 years
12. Relevant cardiac or pulmonary disorders
13. Severe intercurrent neurological or psychiatric disorders
14. Macrophage activation syndrome (MAS) as part of previous treatment with IL-1 blockade (e.g. anakinra, rilonacept)
15. Vaccination with a live vaccine within 3 months before the baseline
16. Alcohol or drug abuse in the past 12 months
17. ≥400 milliliter (mL) donation of blood or loss up to 8 weeks before the baseline
18. Pregnancy or breast-feeding
19. Commitment of the patient to an institution at the direction of an authority or court

Contacts and Locations

Locations

Germany

Charité Campus Mitte

Berlin, Germany, 10117

Immanuel Krankenhaus Berlin

Berlin, Germany, 13125

Universität Erlangen

Erlangen, Germany, 91054

Kliniken Essen-Süd/Krankenhaus St. Josef

Essen, Germany, 45239

Universitätsklinikum der J.W. Goethe-Universität Frankfurt

Frankfurt a. M., Germany, 60590

Asklepios Klinikum Hamburg Altona

Hamburg, Germany, 22763

Medizinische Hochschule Hannover

Hannover, Germany, 30625

Universitätsklinikum Heidelberg

Heidelberg, Germany, 69120

Universitätskrankenhaus Schleswig Holstein

Kiel, Germany, 24105

Med. Klinik I für Innere Medizin Köln

Köln, Germany, 50937

Klinikum der Universität München

München, Germany, 80336

Klinikum Südstadt Rostock

Rostock, Germany, 18059

Universitätsklinikum Tübingen

Tübingen, Germany, 72076

Fachkrankenhaus

Vogelsang, Germany, 39245

Sponsors and Collaborators

Charite University, Berlin, Germany

Investigators

• Principal Investigator: Eugen Feist, Prof. Dr.; Charité University Berlin Germany

  Study Documents (Full-Text)

Documents provided by Eugen Feist, Charite University, Berlin, Germany:

Study Protocol  [PDF] October 20, 2017

Statistical Analysis Plan  [PDF] May 9, 2018

More Information

Additional Information:

Related Info 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Nirmala N, Brachat A, Feist E, Blank N, Specker C, Witt M, Zernicke J, Martini A, Junge G. Gene-expression analysis of adult-onset Still's disease and systemic juvenile idiopathic arthritis is consistent with a continuum of a single disease entity. Pediatr Rheumatol Online J. 2015 Nov 20;13:50. doi: 10.1186/s12969-015-0047-3.

• Responsible Party: Eugen Feist, Prof. Dr Eugen Feist, Charite University, Berlin, Germany
• ClinicalTrials.gov Identifier: NCT02204293
• Other Study ID Numbers: CACZ885GDE01T; 2011-001027-20 ( EudraCT Number )
• First Posted: July 30, 2014
• Results First Posted: August 7, 2020
• Last Update Posted: August 7, 2020
• Last Verified: July 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Eugen Feist, Charite University, Berlin, Germany:

Adult-Onset Still´s Disease; Canakinumab; Joint involvement; AOSD

Additional relevant MeSH terms:

Arthritis, Juvenile; Still's Disease, Adult-Onset; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Arthritis, Rheumatoid