Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

An Efficacy And Safety Study Evaluating Tofacitinib With And Without Methotrexate Compared To Adalimumab With Methotrexate (ORAL STRATEGY)

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: NCT02187055
Recruitment Status : Completed
First Posted : July 10, 2014
Results First Posted : June 27, 2018
Last Update Posted : June 27, 2018
Sponsor:
Information provided by (Responsible Party):
Pfizer

Brief Summary:
To assess the efficacy of tofacitinib monotherapy or tofacitinib with methotrexate as compared to adalimumab with methotrexate. To compare the efficacy of tofacitinib monotherapy compared to tofacitinib combined with methotrexate. To compare effects on all health outcomes measures in the study. To evaluate the safety and tolerability of tofacitinib and adalimumab. To evaluate the safety of the zoster vaccine given prior to the initiation of tofacitinb or adalimumab.

Condition or disease Intervention/treatment Phase
Rhematoid Arthritis Drug: Tofacitinib with methotrexate Drug: Tofacitinib without methotrexate Biological: Adalimumab with methotrexate Phase 4

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1152 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3b/4 Randomized Double Blind Study Of 5 Mg Of Tofacitinib With And Without Methotrexate In Comparison To Adalimumab With Methotrexate In Subjects With Moderately To Severely Active Rheumatoid Arthritis
Actual Study Start Date : August 2014
Actual Primary Completion Date : December 2016
Actual Study Completion Date : December 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Arthritis

Arm Intervention/treatment
Experimental: Tofacitinib 5 mg twice daily with methotrexate Drug: Tofacitinib with methotrexate
Tofacitinib 5 mg twice daily, oral for 12 months Methotrexate (previous stable dose 15-25 mg) every week, oral for 12 months Placebo for adalimumab every other week, subcutaneous for 12 months

Experimental: Tofacitinib 5 mg twice daily monotherapy Drug: Tofacitinib without methotrexate
Tofacitinib 5 mg twice daily, oral for 12 months Placebo for methotrexate (previous stable dose) every week, oral for 12 months Placebo for adalimumab every other week, subcutaneous for 12 months

Active Comparator: Adalimumab with methotrexate Biological: Adalimumab with methotrexate
Placebo for tofacitinib twice daily, oral for 12 months Methotrexate (previous stable dose 15-25 mg) every week, oral for 12 months Adalimumab 40 mg every other week, subcutaneous for 12 months




Primary Outcome Measures :
  1. Percentage of Participants Achieving American College of Rheumatology Criteria 50% Improvement (ACR50) Response at Month 6 [ Time Frame: Month 6 ]
    ACR50 is a greater than or equal to (≥) 50 percent (%) improvement in tender joint count (TJC) or swollen joint count (SJC) and 50% improvement in 3 of the following 5 criteria: 1) physician's global assessment (PGA) of disease activity, 2) participant's assessment (PtGA) of disease activity, 3) participant's assessment of pain, 4) participant's assessment of functional disability via a health assessment questionnaire, and 5) C-reactive protein (CRP) at each visit.


Secondary Outcome Measures :
  1. Change From Baseline in Simplified Disease Activity Index (SDAI) Value at Month 6 [ Time Frame: Month 6 ]
    SDAI is the numerical sum of five outcome parameters: TJC and SJC both based on a 28-joint assessment, PtGA and PGA both assessed on a 0 to 10 centimeter (cm) visual analogue scale (VAS) (higher scores indicate greater affection due to disease activity), and CRP (mg/dL). SDAI total score ranges from 0 to 86. SDAI less than or equal to (≤) 3.3 indicates disease remission, >3.4 to 11 indicates low disease activity, >11 to 26 indicates moderate disease activity, and >26 indicates high disease activity.

  2. Change From Baseline in Clinical Disease Activity Index (CDAI) Value at Month 6 [ Time Frame: Month 6 ]
    CDAI is the numerical sum of four outcome parameters: TJC and SJC both based on a 28-joint assessment, PtGA and PGA both assessed on a 0 to 10 cm VAS (higher scores indicate greater affection due to disease activity). CDAI total score ranges from 0 to 76. CDAI ≤2.8 indicates disease remission, >2.8 to 10 indicates low disease activity, >10 to 22 indicates moderate disease activity, and >22 indicates high disease activity.

  3. Change From Baseline in Disease Activity Score 28-4 (DAS28-4) Including CRP at Month 6 [ Time Frame: Month 6 ]
    DAS28-4 (CRP) was calculated from the SJC and TJC (both based on a 28-joint assessment), PtGA (assessed on a 0 to 10 cm VAS; higher scores indicate greater affection due to disease activity) and CRP (mg/L) using the following: DAS28-4(CRP) = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.36*ln(CRP+1) + 0.014* PtGA (millimeters [mm]) + 0.96. Total score range: 0 to 9.4, higher score indicated higher disease activity. DAS28-4 (CRP) ≤3.2 indicates low disease activity, >3.2 to 5.1 indicates moderate to high disease activity, and less than (<) 2.6 indicates remission.

  4. Change From Baseline in Disease Activity Score 28-4 (DAS28-4) Including Erythrocyte Sedimentation Rate (ESR) at Month 6 [ Time Frame: Month 6 ]
    DAS28-4 (ESR) was calculated from the SJC and TJC (both based on a 28-joint assessment), PtGA (assessed on a 0 to 10 cm VAS; higher scores indicate greater affection due to disease activity) and ESR (mm/hour) using the following: DAS28-4(ESR) = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.70*ln(ESR) + 0.014* PtGA (mm). Total score range: 0 to 9.4, higher score indicated higher disease activity. DAS28-3 (ESR) ≤3.2 indicates low disease activity, >3.2 to 5.1 indicates moderate to high disease activity, and <2.6 indicates remission.

  5. Percentage of Participants Achieving Observed American College of Rheumatology-European League Against Rheumatism (ACR-EULAR) Boolean Remission Criteria at Month 6 [ Time Frame: Month 6 ]
    To meet the ACR-EULAR Boolean remission criteria, a participant must satisfy all of the following: TJC ≤1 and SJC ≤1 (both based on a 28-joint assessment), CRP ≤1 mg/dL, and PtGA ≤1 on a 0 to 10 cm VAS (higher scores indicate greater affection due to disease activity).

  6. Percentage of Participants Achieving SDAI ≤3.3 at Month 6 [ Time Frame: Month 6 ]
    SDAI is the numerical sum of five outcome parameters: TJC and SJC both based on a 28-joint assessment, PtGA and PGA both assessed on a 0 to 10 cm VAS (higher scores indicate greater affection due to disease activity), and CRP (mg/dL). SDAI total score ranges from 0 to 86. SDAI ≤3.3 indicates disease remission.

  7. Percentage of Participants Achieving CDAI ≤2.8 at Month 6 [ Time Frame: Month 6 ]
    CDAI is the numerical sum of four outcome parameters: TJC and SJC both based on a 28-joint assessment, PtGA and PGA both assessed on a 0 to 10 cm VAS (higher scores indicate greater affection due to disease activity). CDAI total score ranges from 0 to 76. CDAI ≤2.8 indicates disease remission.

  8. Percentage of Participants Achieving DAS28-4 (ESR) <2.6 at Month 6 [ Time Frame: Month 6 ]
    DAS28-4 (ESR) was calculated from the SJC and TJC (both based on a 28-joint assessment), PtGA (assessed on a 0 to 10 cm VAS; higher scores indicate greater affection due to disease activity) and ESR (mm/hour) using the following: DAS28-4(ESR) = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.70*ln(ESR) + 0.014* PtGA (mm). Total score range: 0 to 9.4, higher score indicates higher disease activity. DAS28-4 (ESR) <2.6 indicates disease remission.

  9. Percentage of Participants Achieving DAS28-4 (CRP) <2.6 at Month 6 [ Time Frame: Month 6 ]
    DAS28-4 (CRP) was calculated from the SJC and TJC (both based on a 28-joint assessment), PtGA (assessed on a 0 to 10 cm VAS; higher scores indicate greater affection due to disease activity) and CRP (mg/L) using the following: DAS28-4(CRP) = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.36*ln(CRP+1) + 0.014* PtGA (mm) + 0.96. Total score range: 0 to 9.4, higher score indicates higher disease activity. DAS28-4 (CRP) <2.6 indicates remission.

  10. Percentage of Participants Achieving SDAI ≤11 at Month 6 [ Time Frame: Month 6 ]
    SDAI is the numerical sum of five outcome parameters: TJC and SJC both based on a 28-joint assessment, PtGA and PGA both assessed on a 0 to 10 cm VAS (higher scores indicate greater affection due to disease activity), and CRP (mg/dL). SDAI total score ranges from 0 to 86. SDAI ≤3.3 indicates disease remission, >3.4 to 11 indicates low disease activity.

  11. Percentage of Participants Achieving CDAI ≤10 at Month 6 [ Time Frame: Month 6 ]
    CDAI is the numerical sum of four outcome parameters: TJC and SJC both based on a 28-joint assessment, PtGA and PGA both assessed on a 0 to 10 cm VAS (higher scores indicate greater affection due to disease activity). CDAI total score ranges from 0 to 76. CDAI ≤2.8 indicates disease remission, >2.8 to 10 indicates low disease activity.

  12. Percentage of Participants Achieving DAS28-4 (ESR) ≤3.2 at Month 6 [ Time Frame: Month 6 ]
    DAS28-4 (ESR) was calculated from the SJC and TJC (both based on a 28-joint assessment), PtGA (assessed on a 0 to 10 cm VAS; higher scores indicate greater affection due to disease activity) and ESR (mm/hour) using the following: DAS28-4(ESR) = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.70*ln(ESR) + 0.014* PtGA (mm). Total score range: 0 to 9.4, higher score indicates higher disease activity. DAS28-4 (ESR) ≤3.2 indicates low disease activity.

  13. Percentage of Participants Achieving DAS28-4 (CRP) ≤3.2 at Month 6 [ Time Frame: Month 6 ]
    DAS28-4 (CRP) was calculated from the SJC and TJC (both based on a 28-joint assessment), PtGA (assessed on a 0 to 10 cm VAS; higher scores indicate greater affection due to disease activity) and CRP (mg/L) using the following: DAS28-4(CRP) = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.36*ln(CRP+1) + 0.014* PtGA + 0.96. Total score range: 0 to 9.4, higher score indicated higher disease activity. DAS28-4 (CRP) ≤3.2 indicates low disease activity.

  14. Percentage of Participants Achieving American College of Rheumatology Criteria 20% Improvement (ACR20) Response at Month 6 [ Time Frame: Month 6 ]
    ACR20 response is a ≥20% improvement in TJC or SJC and 20% improvement in 3 of the following 5 criteria: 1) PGA of disease activity, 2) PtGA of disease activity, 3) participant's assessment of pain, 4) participant's assessment of functional disability via a health assessment questionnaire, and 5) CRP at each visit.

  15. Percentage of Participants Achieving American College of Rheumatology Criteria 70% Improvement (ACR70) Response at Month 6 [ Time Frame: Month 6 ]
    ACR70 response is a ≥70% improvement in TJC or SJC and 70% improvement in 3 of the following 5 criteria: 1) PGA of disease activity, 2) PtGA of disease activity, 3) participant's assessment of pain, 4) participant's assessment of functional disability via a health assessment questionnaire, and 5) CRP at each visit.

  16. Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Month 6 [ Time Frame: Month 6 ]
    The HAQ-DI is a participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dressing and grooming, arising, eating, walking, reach, grip, hygiene and other activities over the past week. Each activity category consists of 2 to 3 items. Each item is scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Any activity requiring assistance from another individual or the use of an assistive device adjusts to a minimum score of 2 to represent a more limited functional status. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score ranges from 0 to 3 where 0 = least difficulty and 3 = extreme difficulty.

  17. Percentage of Participants Achieving an HAQ-DI Decrease of at Least 0.22 at Month 6 [ Time Frame: Month 6 ]
    The HAQ-DI is a participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dressing and grooming, arising, eating, walking, reach, grip, hygiene and other activities over the past week. Each activity category consists of 2 to 3 items. Each item is scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Any activity requiring assistance from another individual or the use of an assistive device adjusts to a minimum score of 2 to represent a more limited functional status. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score ranges from 0 to 3 where 0 = least difficulty and 3 = extreme difficulty. A decrease of 0.22 or more is considered a positive response.

  18. Change From Baseline in the Short-Form-36 (SF-36) Health Survey, Physical Component Score at Month 6 [ Time Frame: Month 6 ]
    The SF-36 health survey is a 36-item measure that evaluates 8 domains: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. The health domains are aggregated into two summary scores known as the physical component summary (PCS) score and the mental component summary (MCS) score. Normalized domain scores, PCS and MCS scores are used in the analyses. The component and domain scores were scored using the United States (US) 1998 general population norms. The resulting norm-based scores for both the SF-36 version 2 (v2) and SF-36 health domain scales and component summary measures have means of 50 and standard deviations of 10. A higher PCS score represents better physical health status.

  19. Change From Baseline in the SF-36 Health Survey, Mental Component Score at Month 6 [ Time Frame: Month 6 ]
    The SF-36 health survey is a 36-item measure that evaluates 8 domains: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. The health domains are aggregated into two summary scores known as the PCS score and the MCS score. Normalized domain scores, PCS and MCS scores are used in the analyses. The component and domain scores were scored using the US 1998 general population norms. The resulting norm-based scores for both the SF-36 v2 and SF-36 health domain scales and component summary measures have means of 50 and standard deviations of 10. A higher MCS score represents better physical health status.

  20. Change From Baseline in the SF-36 Health Survey, Physical Functioning Domain Score at Month 6 [ Time Frame: Month 6 ]
    SF-36v2 acute is a 36-item measure evaluating 8 domains: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. The 10 items of the physical functioning scale represent levels and kinds of limitations between extremes of physical activities, including lifting and carrying groceries; climbing stairs; bending, kneeling, or stooping; walking moderate distances; self-care limitations. The physical functioning items capture the presence and extent of physical limitations using a 3-level response continuum. The domain scores were scored using the US 1998 general population norms. The resulting norm-based scores for both the SF-36 v2 and SF-36 health domain scales and component summary measures have means of 50 and standard deviations of 10. A higher physical functioning domain score represents better physical functioning.

  21. Change From Baseline in the SF-36 Health Survey, Role Physical Domain Score at Month 6 [ Time Frame: Month 6 ]
    SF-36v2 acute is a 36-item measure evaluating 8 domains: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. The 4-item role physical scale covers an array of physical health-related role limitations, including: a) limitations in the kind of work or other usual activities; b) reductions in the amount of time spent on work or other usual activities; c) difficulty performing work or other usual activities; and d) accomplishing less. Items in the role physical scale are answered on a 5-point scale. The domain scores were scored using the US 1998 general population norms. The resulting norm-based scores for both the SF-36 v2 and SF-36 health domain scales and component summary measures have means of 50 and standard deviations of 10. A higher role physical domain score represents better role physical functioning.

  22. Change From Baseline in the SF-36 Health Survey, Bodily Pain Domain Score at Month 6 [ Time Frame: Month 6 ]
    The SF-36v2 acute is a 36-item measure that evaluates 8 domains: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. The bodily pain scale comprises of 2 items pertaining to the intensity of bodily pain and extent of interference with normal work activities. The domain scores were scored using the US 1998 general population norms. The resulting norm-based scores for both the SF-36 v2 and SF-36 health domain scales and component summary measures have means of 50 and standard deviations of 10. A higher bodily pain domain score represents less bodily pain.

  23. Change From Baseline in the SF-36 Health Survey, General Health Domain Score at Month 6 [ Time Frame: Month 6 ]
    The SF-36v2 acute is a 36-item measure that evaluates 8 domains: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. The general health scale consists of 5 items including a rating of health and 4 items addressing the respondent's view and expectations of his or her health. The domain scores were scored using the US 1998 general population norms. The resulting norm-based scores for both the SF-36 v2 and SF-36 health domain scales and component summary measures have means of 50 and standard deviations of 10. A higher general health domain score represents better general health perceptions.

  24. Change From Baseline in the SF-36 Health Survey, Vitality Domain Score at Month 6 [ Time Frame: Month 6 ]
    The SF-36v2 acute is a 36-item measure that evaluates 8 domains: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. The 4-item measure of vitality captures a broad range of subjective evaluations of well-being from feelings of tiredness and being worn out to feeling full of energy all or most of the time. The domain scores were scored using the US 1998 general population norms. The resulting norm-based scores for both the SF-36 v2 and SF-36 health domain scales and component summary measures have means of 50 and standard deviations of 10. A higher vitality domain score represents better vitality.

  25. Change From Baseline in the SF-36 Health Survey, Social Functioning Domain Score at Month 6 [ Time Frame: Month 6 ]
    The SF-36v2 acute is a 36-item measure that evaluates 8 domains: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. The 2-item social functioning scale assesses health-related effects on quantity and quality of social activities. The domain scores were scored using the US 1998 general population norms. The resulting norm-based scores for both the SF-36 v2 and SF-36 health domain scales and component summary measures have means of 50 and standard deviations of 10. A higher social functioning domain score represents better social functioning.

  26. Change From Baseline in the SF-36 Health Survey, Role Emotional Domain Score at Month 6 [ Time Frame: Month 6 ]
    The SF-36v2 acute is a 36-item measure that evaluates 8 domains: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. The 3-item role emotional scale assesses mental health-related role limitations in terms of a) time spent in work or other usual activities; b) amount of work or activities accomplished; c) care with which work or other activities were performed. All 3 items are answered on a 5-point scale. The domain scores were scored using the US 1998 general population norms. The resulting norm-based scores for both the SF-36 v2 and SF-36 health domain scales and component summary measures have means of 50 and standard deviations of 10. A higher role emotional domain score represents better role emotional functioning.

  27. Change From Baseline in the SF-36 Health Survey, Mental Health Domain Score at Month 6 [ Time Frame: Month 6 ]
    The SF-36v2 acute is a 36-item measure that evaluates 8 domains: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. The 5-item mental health scale includes 1 or more items from each of 4 major mental health dimensions: anxiety, depression, loss of behavioral/emotional control, and psychological well-being. All items are answered on a 5-point scale. The domain scores were scored using the US 1998 general population norms. The resulting norm-based scores for both the SF-36 v2 and SF-36 health domain scales and component summary measures have means of 50 and standard deviations of 10. A higher mental health domain score represents better mental health functioning.

  28. Change From Baseline in the Work Productivity and Activity Impairment (WPAI) Questionnaire at Month 6 [ Time Frame: Month 6 ]
    The WPAI: Rheumatoid Arthritis is a 6 item questionnaire that is specific for rheumatoid arthritis and yields four types of scores: absenteeism, presenteesism (impairment at work/reduced job effectiveness), work productivity loss and activity impairment. WPAI outcomes are expressed as impairment percentages ranging from 0 to 100, with higher numbers indicating greater impairment and less productivity.

  29. Change From Baseline in the EuroQol European Quality of Life-5 Dimensions (EuroQol EQ-5D) at Month 6 [ Time Frame: Month 6 ]
    The EQ-5D is a 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"). This profile of scores across the 5-dimensions (e.g. 11231, 33212, etc.) is transformed into a single health utility score using a formula developed by the EuroQol Group that applies country specific preference weights. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. The VAS component rated the current health state on a scale ranging from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicating a better health state.

  30. Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale Total Score at Month 6 [ Time Frame: Month 6 ]
    FACIT-F is a 13-item questionnaire. Participants scored each item on a 5-point scale: 0 (not at all) to 4 (very much). The larger the participant's response (with the exception of 2 negatively stated), the greater the participant's 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).



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:

  • Have moderate to severe rheumatoid arthritis
  • On methotrexate but inadequately controlled
  • Subjects must not have active tuberculosis or an inadequately treated tuberculosis infection
  • Subjects must use contraception

Exclusion Criteria:

  • Subjects who have been previously treated with adalimumab or Tofacitinib
  • Subjects with any current malignancy or a history of malignancy, with the exception of adequately treated or excised non metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ.
  • Subjects with specific laboratory test abnormalities
  • Subjects with specific types of infections

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): NCT02187055


  Show 215 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: NCT02187055     History of Changes
Other Study ID Numbers: A3921187
2014-000358-13 ( EudraCT Number )
ORAL STRATEGY ( Other Identifier: Alias Study Number )
First Posted: July 10, 2014    Key Record Dates
Results First Posted: June 27, 2018
Last Update Posted: June 27, 2018
Last Verified: May 2018
Additional relevant MeSH terms:
Layout table for MeSH terms
Arthritis
Joint Diseases
Musculoskeletal Diseases
Adalimumab
Methotrexate
Tofacitinib
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Anti-Inflammatory Agents
Protein Kinase Inhibitors