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A Phase 2 Study For Patients With A Physician's Diagnosis Of Rheumatoid Arthritis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00550446
Recruitment Status : Completed
First Posted : October 29, 2007
Results First Posted : January 3, 2013
Last Update Posted : January 3, 2013
Sponsor:
Information provided by (Responsible Party):
Pfizer

Brief Summary:
The purpose of this study is to determine the effectiveness and safety, over 6 months, of 5 doses of CP-690,550 for the treatment of adults with active rheumatoid arthritis. Five out of seven subjects will receive CP-690,550. One out of seven will receive adalimumab (Humira®) and one out of seven will only receive inactive substances (placebo.)

Condition or disease Intervention/treatment Phase
Arthritis, Rheumatoid Drug: Adalimumab Drug: CP-690-550 Drug: CP-690,550 Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 386 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2b, Randomized, Double Blind, Placebo Controlled Active Comparator, Multicenter Study To Compare 5 Dose Regimens Of CP- 690,550 And Adalimumab Versus Placebo, Administered For 6 Months In The Treatment Of Subjects With Active Rheumatoid Arthritis
Study Start Date : September 2007
Actual Primary Completion Date : January 2009
Actual Study Completion Date : January 2009

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: 1 Drug: Adalimumab
40mg subcutaneous injections every other week for 6 injections during week 0-10 with oral placebo BID. Subjects switched to CP-690,550 at week 12.

Experimental: 2 Drug: CP-690-550
15 mg BID oral plus 6 placebo subcutaneous injections (week 0-10)

Experimental: 3 Drug: CP-690-550
10 mg BID oral plus 6 placebo subcutaneous injections (week 0-10)

Experimental: 4 Drug: CP-690-550
5 mg BID oral plus 6 placebo subcutaneous injections (week 0-10)

Experimental: 5 Drug: CP-690,550
3 mg BID PO plus 6 placebo subcutaneous injections (week 0-10)

Experimental: 6 Drug: CP-690,550
1 mg BID PO plus 6 placebo subcutaneous injections (week 0-10)

Placebo Comparator: 7 Drug: Placebo
Placebo by mouth plus 6 placebo subcutaneous injections (week 0-10)




Primary Outcome Measures :
  1. Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Week 12 [ Time Frame: Week 12 ]
    ACR20 response: greater than or equal to (>=) 20 % improvement in tender joint count (TJC); >= 20% improvement in swollen joint count (SJC); and >= 20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and C-Reactive Protein (CRP).


Secondary Outcome Measures :
  1. Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response [ Time Frame: Week 2, 4, 6, 8, 10, 16, 20 and 24/Early Termination (ET) ]
    ACR20 response: 20% improvement in TJC; >=20% improvement in SJC; and >=20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and CRP.

  2. Percentage of Participants Achieving American College of Rheumatology 50%(ACR50) Response [ Time Frame: Week 2, 4, 6, 8, 10, 12, 16, 20 and 24/ET ]
    ACR50 response: >= 50% improvement in TJC or SJC and 50% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and CRP.

  3. Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response [ Time Frame: Week 2, 4, 6, 8, 10, 12, 16, 20 and 24/ET ]
    ACR70 response: >= 70% improvement in TJC or SJC and 70% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and CRP.

  4. Percentage of Participants Achieving American College of Rheumatology 90% (ACR90) Response [ Time Frame: Week 2, 4, 6, 8, 10, 12, 16, 20 and 24/ET ]
    ACR90 response: >= 90% improvement in TJC or SJC and 90% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and CRP.

  5. Area Under the Numeric Index of American College of Rheumatology Response (ACR-n) Curve [ Time Frame: Baseline up to Week 2, 4, 6, 8, 10, 12 ]
    ACR-n = calculated for each participant by taking the lowest percentage improvement in (1) SJC or (2) TJC or (3) the median of the remaining 5 components of the ACR response (participant's assessment of disease activity; participant's global assessment of pain; physician's assessment of disease activity; participant's assessment of physical function; an acute phase reactant value - CRP). Negative numbers indicate worsening. Area under the curve (AUC) for ACR-n is the measure of the area under the curve of the mean change from baseline in ACR-n. The trapezoidal rule was used to compute the AUC.

  6. Tender Joint Count (TJC) [ Time Frame: Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20 and 24/ET ]
    Number of tender joints was determined by examining 68 joints and identified the joints that were painful under pressure or to passive motion. The number of tender joints was recorded on the joint assessment form at each visit, no tenderness = 0, tenderness = 1.

  7. Change From Baseline in Tender Joint Count at Week 2, 4, 6, 8, 10, 12, 16, 20 and 24 or ET [ Time Frame: Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20 and 24/ET ]
    Number of tender joints was determined by examining 68 joints and identified the joints that were painful under pressure or to passive motion. The number of tender joints was recorded on the joint assessment form at each visit, no tenderness = 0, tenderness = 1. A negative value in change from baseline indicated an improvement.

  8. Swollen Joint Counts (SJC) [ Time Frame: Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20 and 24/ET ]
    Number of swollen joints was determined by examination of 66 joints and identifying when swelling was present. The number of swollen joints was recorded on the joint assessment form at each visit, no swelling = 0, swelling =1.

  9. Change From Baseline in Swollen Joint Count at Week 2, 4, 6, 8, 10, 12, 16, 20 and 24 [ Time Frame: Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20 and 24/ET ]
    Number of swollen joints was determined by examination of 66 joints and identifying when swelling was present. The number of swollen joints was recorded on the joint assessment form at each visit, no swelling = 0, swelling = 1. A negative value in change from baseline indicated an improvement.

  10. Patient Assessment of Arthritis Pain [ Time Frame: Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20, 24/ET ]
    Participants rated the severity of arthritis pain on a 0 to 100 millimeter (mm) Visual Analog Scale (VAS), where 0 mm = no pain and 100 mm = most severe pain.

  11. Change From Baseline in Patient Assessment of Arthritis Pain at Week 2, 4, 6, 8, 10, 12, 16, 20 and 24/ET [ Time Frame: Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20 and 24/ET ]
    Participants rated the severity of arthritis pain on a 0 to 100 millimeter (mm) Visual Analog Scale (VAS), where 0 mm = no pain and 100 mm = most severe pain.

  12. Patient Global Assessment (PtGA) of Arthritis Pain [ Time Frame: Baseline, 2, 4, 6, 8, 10, 12, 16, 20, 24/ET ]
    Participants answered: "Considering all the ways your arthritis affects you, how are you feeling today?" Participants responded by using a 0 - 100 mm VAS, where 0 mm = very well and 100 mm = very poorly.

  13. Change From Baseline in Patient Global Assessment (PtGA) of Arthritis at Week 2, 4, 6, 8, 10, 12, 16, 20 and 24/ET [ Time Frame: Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20, 24/ET ]
    Participants answered: "Considering all the ways your arthritis affects you, how are you feeling today?" Participants responded by using a 0 - 100 mm VAS, where 0 mm = very well and 100 mm = very poorly.

  14. Physician Global Assessment (PGA) of Arthritis [ Time Frame: Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20, 24/ET ]
    Physician global assessment of arthritis was measured on a 0 to 100 mm VAS, where 0 mm = very good and 100 mm = very bad.

  15. Change From Baseline in Physician's Global Assessment (PGA) of Arthritis Pain at Week 2, 4, 6, 8, 10, 12, 16, 20 and 24/ET [ Time Frame: Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20, 24/ET ]
    Physician global assessment of arthritis was measured on a 0 to 100 mm VAS, where 0 mm = very good and 100 mm = very bad.

  16. C-Reactive Protein (CRP) [ Time Frame: Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20, 24/ET ]
    The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. Normal range of CRP is 0 milligram per liter (mg/L) to 10 mg/L. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement.

  17. Change From Baseline in C-reactive Protein (CRP) at Week 2, 4, 6, 8, 10, 12, 16, 20 and 24/ET [ Time Frame: Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20, 24/ET ]
    The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. Normal range of CRP is 0 mg/L to 10 mg/L. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement.

  18. Health Assessment Questionnaire-Disability Index (HAQ-DI) [ Time Frame: Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20, 24/ET ]
    HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.

  19. Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 2, 4, 6, 8, 10, 12, 16, 20 and 24/ET [ Time Frame: Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20, 24/ET ]
    HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.

  20. Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) [ Time Frame: Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20, 24/ ET ]
    DAS28-3 (CRP) was calculated from the SJC and TJC using the 28 joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3 (CRP) less than or equal to (<=) 3.2 implied low disease activity and greater than (>) 3.2 to 5.1 implied moderate to high disease activity, and less than (<) 2.6 = remission.

  21. Change From Baseline in Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) at Week 2, 4, 6, 8, 10, 12, 16, 20 and 24/ET [ Time Frame: Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20, 24/ ET ]
    DAS28-3 (CRP) was calculated from the SJC and TJC using the 28 joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3 (CRP) <= 3.2 implied low disease activity and > 3.2 to 5.1 implied moderate to high disease activity, and < 2.6 = remission.

  22. Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) [ Time Frame: Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20, 24/ ET ]
    DAS28-4 (ESR) calculated from SJC and TJC using 28 joint count, erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hour]) and PtGA of disease activity (transformed score ranging 0 to 10; higher score indicated greater affectation due to disease activity). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-4 (ESR) <= 3.2 implies low disease activity and > 3.2 to 5.1 implies moderate to high disease activity, and < 2.6 = remission.

  23. Change From Baseline in Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) at Week 2, 4, 6, 8, 12, 16, 20 and 24/ET [ Time Frame: Baseline, Week 2, 4, 6, 8, 10, 12, 16, 20, 24/ET ]
    DAS28-4 (ESR) calculated from SJC and TJC using 28 joint count, ESR [mm/hour] and PtGA of disease activity (transformed score ranging 0 to 10; higher score indicated greater affectation due to disease activity). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-4 (ESR) <= 3.2 implies low disease activity and > 3.2 to 5.1 implies moderate to high disease activity, and < 2.6 = remission.

  24. Percentage of Participants With Disease Improvement Based on DAS28-4 (ESR) [ Time Frame: Week 2, 4, 6, 8, 10, 12, 16, 20, 24/ET ]
    Disease improvement was classified as good, moderate, and none based on improvement in DAS28-4 (ESR) from baseline and present DAS28-4 (ESR) score. Good: an improvement from baseline of >1.2 and a present score of <=3.2; none: an improvement of <=0.6 or >0.6 to <=1.2 with a present score of >5.1; remaining participants were classified as having moderate (Mod) improvement. Scores of good and moderate were considered to have therapeutic response.

  25. Percentage of Participants With Disease Remission Based on Normal C-reactive Protein (CRP) [ Time Frame: Week 2, 4, 6, 8, 10, 12, 16, 20, 24/ ET ]
    CRP value less than or equal to upper limit of normal (ULN) implied disease remission (ULN=4.9 mg/L).

  26. Percentage of Participants With Disease Remission Based on DAS28-3 (CRP) [ Time Frame: Week 2, 4, 6, 8, 10, 12, 16, 20, 24/ ET ]
    DAS28-3 (CRP) defined remission was classified as a score of <2.6.

  27. 36-Item Short-Form Health Survey (SF-36) [ Time Frame: Baseline, Week 12, 24/ ET ]
    SF-36 is a standardized survey evaluating 8 domains (of 2 components [C]; physical [Ph] and mental [Mn]) of functional health and well being: physical and social (So) functioning (Fn), physical and emotional role (role-physical [R-P], role-emotional [R-E]) limitations, bodily pain (BP), general health (GH), vitality (Vit), mental health (MnH). The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning).

  28. Change From Baseline in 36-Item Short-Form Health Survey (SF-36) at Week 12 and 24/ET [ Time Frame: Baseline, Week 12, 24/ ET ]
    SF-36 is a standardized survey evaluating 8 domains (of 2 components [C]; physical [Ph] and mental [Mn]) of functional health and well being: physical and social (So) functioning (Fn), physical and emotional role (role-physical [R-P], role-emotional [R-E]) limitations, bodily pain (BP), general health (GH), vitality (Vit), mental health (MnH). The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning).

  29. Euro Quality of Life 5 Dimension (EQ-5D)-Health State Profile Utility Score [ Time Frame: Baseline, Week 12, 24/ ET ]
    EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state (confined to bed). Scoring formula developed by EuroQoL Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state.

  30. Change From Baseline in Euro Quality of Life 5 Dimension (EQ-5D)- Health State Profile Utility Score at Week 12 and 24/ET [ Time Frame: Baseline, Week 12, 24/ ET ]
    EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state ("confined to bed"). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state.


Other Outcome Measures:
  1. Serum Immunoglobulin G (IgG), Immunoglobulin M (IgM) and Immunoglobulin A (IgA) Levels [ Time Frame: Baseline, Week 24/ ET ]
    Blood samples for immunoglobulin assessments were obtained to determine IgG, IgM, and IgA levels in serum.

  2. Change From Baseline in Serum Immunoglobulin G (IgG), Immunoglobulin M (IgM) and Immunoglobulin A (IgA) Levels at Week 24 [ Time Frame: Baseline, Week 24/ ET ]
    Blood samples for immunoglobulin assessments were obtained to determine change from baseline in serum IgG, IgM, and IgA levels.

  3. Fluorescence Activated Cell Sorting (FACS) Lymphocyte Biomarkers [ Time Frame: Baseline, Week 24/ ET ]
    The following biomarkers were assessed: Cluster of Differentiation 3 (CD3), CD4, CD8, CD19 and CD56. FACS analysis for lymphocyte subset markers were used to assess the effects of repeated doses of CP-690,550.

  4. Change From Baseline in Fluorescence Activated Cell Sorting (FACS) Lymphocyte Biomarkers at Week 24 [ Time Frame: Baseline, Week 24/ ET ]
    The following biomarkers were assessed: CD3, CD4, CD8, CD19 and CD56. FACS analysis for lymphocyte subset markers were used to assess the effects of repeated doses of CP-690,550.

  5. Medical Outcome Study- Sleep Scale (MOS-SS) [ Time Frame: Baseline, Week 2, 12, 24/ ET ]
    Participant-rated questionnaire to assess key constructs of sleep over the past week. Consists of a 12-item based on 7 sub scales: sleep disturbance (SD), snoring (Sno), awakened short of breath (ASOB) or with headache, sleep adequacy (Ade), and somnolence (Som) (range:0-100); sleep quantity (Qua)(range:0-24), and optimal (Opt) sleep (yes: 1, no: 0)and nine item index measures of sleep disturbance were constructed to provide composite scores: sleep problem summary (SPS) and overall sleep problems (OSP). Except sleep adequacy, optimal sleep and quantity, higher scores=greater impairment. Scores are transformed (actual raw score minus lowest possible score divided by possible raw score range* 100); total score range: 0 to 100; higher score = greater intensity of attribute.

  6. Change From Baseline in Medical Outcome Study- Sleep Scale (MOS-SS) at Week 2, 12 and 24/ET [ Time Frame: Baseline, Week 2, 12, 24/ ET ]
    Participant-rated questionnaire to assess key constructs of sleep over the past week. Consists of a 12-item based on 7 subscales: sleep disturbance (SD), snoring (Sno), awakened short of breath (A SOB) or with headache, sleep adequacy (Ade), and somnolence (Som) (range: 0-100); sleep quantity (Qua) (range: 0-24), and optimal (Opt) sleep (yes: 1, no: 0) and 9 item index measures of sleep disturbance were constructed to provide 2 composite scores: sleep problem summary (SPS) and overall sleep problems (OSP). Except sleep adequacy, optimal sleep and quantity, higher scores=greater impairment. Scores are transformed (actual raw score minus lowest possible score divided by possible raw score range*100); total score range: 0 to 100; higher score = greater intensity of attribute.

  7. Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale [ Time Frame: Baseline, Week 2, 12, 24/ ET ]
    FACIT-Fatigue is a 13-item questionnaire. Participant scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as 4 minus the participant's response. The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). A higher score reflected an improvement in the participant's health status.

  8. Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale at Week 2, 12 and 24/ET [ Time Frame: Baseline, Week 2, 12, 24/ ET ]
    FACIT-Fatigue is a 13-item questionnaire. Participant scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as 4 minus the participant's response. The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). A higher score reflected an improvement in the participant's health status.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects must have active rheumatoid arthritis
  • Subjects must have failed at least 1 disease modifying anti-rheumatic drug (DMARD)
  • Subjects must not be currently taking any DMARD other than an antimalarial

Exclusion Criteria:

  • Subjects who discontinued any previous TNF inhibitor therapy for either lack of benefit or safety.
  • Subjects who previously received adalimumab (Humira®) therapy for any reason.
  • Subjects with evidence of blood disorders, chronic infections or untreated tuberculosis

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00550446


Locations
Show Show 63 study locations
Sponsors and Collaborators
Pfizer
Investigators
Layout table for investigator information
Study Director: Pfizer CT.gov Call Center Pfizer
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Layout table for additonal information
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00550446    
Other Study ID Numbers: A3921035
First Posted: October 29, 2007    Key Record Dates
Results First Posted: January 3, 2013
Last Update Posted: January 3, 2013
Last Verified: November 2012
Keywords provided by Pfizer:
Janus Kinase 3 Clinical Trial
Additional relevant MeSH terms:
Layout table for MeSH terms
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Adalimumab
Tofacitinib
Tumor Necrosis Factor Inhibitors
Anti-Inflammatory Agents
Antirheumatic Agents
Janus Kinase Inhibitors
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action