Symptoms and General Pathology

All Conditions

Musculoskeletal Diseases

Skin and Connective Tissue Diseases

Immune System Diseases

Necrosis

Arthritis

Arthritis, Rheumatoid

Joint Diseases

Rheumatic Diseases

Collagen Diseases

Connective Tissue Diseases

Autoimmune Diseases

Anti-Inflammatory Agents

All Drugs and Chemicals

Antirheumatic Agents

Analgesics

Gastrointestinal Agents

Tumor Necrosis Factor Inhibitors

Tofacitinib

Etanercept

Adalimumab

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Immunosuppressive Agents

Immunologic Factors

Janus Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

TNF inhibitor Arm - adalimumab will be used in US, Canada and Puerto Rico; etanercept will be used in all other countries.

tofacitinib

Pre-filled syringe, 40 mg subcutaneous injection, every other week

adalimumab

Pre-filled syringe, 50 mg subcutaneous injection, every week

etanercept

Pfizer CT.gov Call Center

This post-marketing study is designed to compare the safety of tofacitinib versus TNF inhibitor with respect to major cardiovascular adverse events and malignancies, excluding non-melanoma skin cancers when given to subjects with rheumatoid arthritis. Other safety events, including non-melanoma skin cancers, hepatic events, infections, and efficacy parameters will be collected and evaluated in the study.

Safety Study Of Tofacitinib Versus Tumor Necrosis Factor (TNF) Inhibitor In Subjects With Rheumatoid Arthritis

PHASE 3B/4 RANDOMIZED SAFETY ENDPOINT STUDY OF 2 DOSES OF TOFACITINIB IN COMPARISON TO A TUMOR NECROSIS FACTOR (TNF) INHIBITOR IN SUBJECTS WITH RHEUMATOID ARTHRITIS

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Incidence rate (number of participants with event per 100 participant year \[PY\]) was defined as the total number of participants with admissible events divided by the total (for all qualifying participants) time at risk for the cohort/treatment group of interest. Malignancy events, excluding NMSC were adjudicated by a steering committee. The risk period (RP) was the last contact date. The last contact date was the maximum of (AE start date, AE stop date, last study visit date, withdrawal date, telephone contact date). If a participant died, last contact date was the death date. First events were counted within the RP. If a participant did not have an event or had an event but outside the risk period, the participant was censored at the end of RP.

MACE included the cardiovascular death, non-fatal myocardial infarction (MI) and non-fatal stroke of any classification, including reversible focal neurologic defects with imaging evidence of a new cerebral lesion consistent with ischemia or hemorrhage. Incidence rate was defined as the total number of participants with admissible events divided by the total (for all qualifying participants) time at risk for the cohort/treatment group of interest. The risk period (RP) was the minimum of last contact date or last study treatment dose date + 60 days. The last contact date was the maximum of (AE start date, AE stop date, last study visit date, withdrawal date, telephone contact date). If a participant died, last contact date was the death date. First events were counted within the RP. If a participant did not have an event or had an event but outside the risk period, the participant was censored at the end of RP.

Non-fatal stroke included reversible focal neurologic defects with imaging evidence of a new cerebral lesion consistent with ischemia or hemorrhage. Incidence rate was defined as the total number of participants with admissible events divided by the total (for all qualifying participants) time at risk for the cohort/treatment group of interest. The risk period (RP) was the minimum of last contact date or last study treatment dose date + 60 days. The last contact date was the maximum of (AE start date, AE stop date, last study visit date, withdrawal date, telephone contact date). If a participant died, last contact date was the death date. First events were counted within the RP. If a participant did not have an event or had an event but outside the risk period, the participant was censored at the end of RP.

Incidence rate was defined as the total number of participants with admissible events divided by the total (for all qualifying participants) time at risk for the cohort/treatment group of interest. The risk period (RP) was the minimum of last contact date or last study treatment dose date + 60 days. The last contact date was the maximum of (AE start date, AE stop date, last study visit date, withdrawal date, telephone contact date). If a participant died, last contact date was the death date. First events were counted within the RP. If a participant did not have an event or had an event but outside the risk period, the participant was censored at the end of RP.

Opportunistic infections (OI) were reviewed and adjudicated by the opportunistic infection review committee (OIRC). Incidence rate was defined as the total number of participants with admissible events divided by the total (for all qualifying participants) time at risk for the cohort/treatment group of interest. The risk period (RP) was the minimum of last contact date or last study treatment dose date + 28 days. The last contact date was the maximum of (AE start date, AE stop date, last study visit date, withdrawal date, telephone contact date). If a participant died, last contact date was the death date. First events were counted within the RP. If a participant did not have an event or had an event but outside the risk period, the participant was censored at the end of RP.

Hepatic events (adjudicated) included drug-induced liver injury (DILI) - probable, highly likely and definite, DILI - listed separately, DILI - cases meeting classification and severity, participants with elevations of transaminase levels greater than (\>) 1\* upper limit of normal (ULN), greater than or equal to (\>=) 3\*ULN, \>=5\*ULN (based on laboratory values). Incidence rate was the total number of participants with admissible events divided by total (for all qualifying participants) time at risk for the cohort/treatment group of interest. The risk period (RP) was minimum of The risk period (RP) was the minimum of last contact date or last study treatment dose date + 28 days. Last contact date was maximum of (AE start date, AE stop date, last study visit date, withdrawal date, telephone contact date). In case of death, last contact date was death date. First events counted within RP. Participant did not have an event or had an event outside risk period were censored at end of RP.

Cardiovascular events (adjudicated) were death (coronary and non-coronary), MI, all coronary revascularization, unstable angina, new ischemic heart disease, stroke (fatal and non-fatal), transient ischemic attack (TIA), congestive heart failure (CHF), peripheral arterial vascular disease (PAVD), deep vein thrombosis, pulmonary embolism, arterial embolism, arterial thrombosis. Incidence rate was total number of participants with admissible events divided by total (for all qualifying participants) time at risk for cohort/treatment group of interest. Risk period (RP) was the minimum of last contact date or last study treatment dose date + 28 days. Last contact date was maximum of (AE start date, AE stop date, last study visit date, withdrawal date, telephone contact date). In case of death, last contact date was death date. First events counted within RP. Participant did not have an event or had an event outside risk period were censored at end of RP.

AE was any untoward medical occurrence post treatment; event need not necessarily had causal relationship with treatment or usage. SAE: any untoward medical occurrence at any dose: resulted in death, life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, resulted in congenital anomaly. TEAE: event that occurred for first time during effective duration of treatment and not seen prior to start of treatment or event seen prior to start of treatment but increase in severity during treatment. Risk period (RP) for AE: minimum of last contact date or last study treatment dose date+28 days. RP for SAEs: last contact date. Last contact date was maximum: AE start, AE stop, last study visit, withdrawal and telephone contact. In case of death, last contact was death date. First events counted within RP. Participant did not have event or had event outside risk period were censored at end of RP.

Clinically significant laboratory abnormalities: Hematology: hemoglobin, hematocrit, erythrocytes with primary criteria as less than \[\<\] 0.8\* lower limit of normal \[LLN\]), platelets (\<0.5\* LLN; \>1.75\* ULN), leukocytes (\<0.6\*LLN; \>1.5\*ULN), lymphocytes, lymphocytes/leukocytes, neutrophils, neutrophils/leukocytes (\<0.8\*LLN; \>1.2\*ULN), eosinophils, eosinophils/leukocytes, monocytes, monocytes/leukocytes (\>1.2\*ULN); urinalysis: urine glucose, urine protein, urine hemoglobin, and leukocyte esterase (\>=1); chemistry: bilirubin, indirect bilirubin (\>1.5\*ULN) aspartate aminotransferase, alanine aminotransferase (\>3.0\*ULN), creatinine, triglycerides, cholesterol (\>1.3\*ULN) and HDL cholesterol (\<0.8\*LLN). Risk period (RP) was minimum of last contact date or last study treatment dose date+28 days. Last contact date was (date of death or maximum of dates: AE start, AE stop, last study visit, withdrawal, telephone contact). Participants without event or event outside RP were censored at end of RP.

All-cause death was defined as the death due to any cause during the course of study. Incidence rate was defined as the total number of participants with admissible events divided by the total (for all qualifying participants) time at risk for the cohort/treatment group of interest. Incidence rate of all-cause deaths (adjudicated by Adjudication Committee) was reported in this outcome measure. The risk period (RP) was the minimum of last contact date or last study treatment dose date + 28 days. The last contact date was the maximum of (AE start date, AE stop date, last study visit date, withdrawal date, telephone contact date). If a participant died, last contact date was the death date. First events were counted within the RP. If a participant did not have an event or had an event but outside the risk period, the participant was censored at the end of RP.

Number of participants who permanent or temporary discontinued study medication due to any AE, treatment related AEs, Coronavirus disease 2019 (COVID 19) related AEs, and herpes zoster were reported. The risk period (RP) was the minimum of last contact date or last study treatment dose date + 28 days. The last contact date was the maximum of (AE start date, AE stop date, last study visit date, withdrawal date, telephone contact date). If a participant died, last contact date was the death date. First events were counted within the RP. If a participant did not have an event or had an event but outside the risk period, the participant was censored at the end of RP.

DAS28 is a measure of disease activity in participants with rheumatoid arthritis based on a 28-joint assessment. DAS28-4 (CRP) was calculated from number of painful joints out of 28 joints (TJC28) and number of swollen joints out of 28 joints (SJC28), CRP (milligrams per liter \[mg/L\]) and patient's global assessment of disease activity (PtGA) on a 100 mm Visual Analog Scale (VAS) (scores ranging from 0 millimeter \[mm\] \[very well\] to 100 mm \[worst\], higher scores indicated worse health condition). Total DAS28-4 (CRP) score range: 0 to 9.4, higher score indicated more disease activity. DAS28-4 (CRP) \<= 3.2 indicates low disease activity and \> 3.2 to \<=5.1 indicates moderate disease activity, \>5.1 indicates high disease activity, and DAS28-4 (CRP) \< 2.6 indicates remission. DAS28-4 (CRP) = 0.56\*sqrt(TJC28) + 0.28\*sqrt(SJC28) + 0.36\*ln(CRP in mg/L +1) + 0.014\*PtGA in mm+ 0.96; ln = natural logarithm, sqrt = square root.

SDAI is the numerical sum of five outcome parameters: TJC and SJC both based on a 28-joint assessment, PtGA and physician's global assessment of health (PhyGA) both assessed on a 0 to 100 mm VAS (higher scores indicate greater affection due to disease activity), and CRP (mg/L). SDAI total score ranges from 0 to 86 with higher score indicating greater disease activity. SDAI \<=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. SDAI = (28TJC) + (28SJC) + PhyGA/10 + PtGA/10 + CRP/10.

CDAI is the numerical sum of four outcome parameters: TJC and SJC both based on a 28-joint assessment, PtGA and PhyGA both assessed on a 0 to 100 mm VAS (higher scores indicate greater affection due to disease activity). CDAI total score ranges from 0 to 76 with higher score indicating greater disease activity. 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. CDAI = (28TJC) + (28SJC) + PhyGA/10 + PtGA/10.

ACR-EULAR Boolean-based definition of remission participant must satisfy all of the following: TJC28 \<=1, SJC28 \<=1, CRP \<=10 mg/L, PtGA on a 0-100 mm scale, higher scores indicate greater affection due to disease activity.

SDAI is the numerical sum of five outcome parameters: TJC and SJC both based on a 28-joint assessment, PtGA and PhyGA both assessed on a 0 to 100 mm VAS (higher scores indicate greater affection due to disease activity), and CRP (mg/L). SDAI total score ranges from 0 to 86 with higher score indicating greater disease activity. SDAI \<=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. SDAI = (28TJC) + (28SJC) + PhyGA/10 + PtGA/10 + CRP/10.

DAS28 is a measure of disease activity in participants with rheumatoid arthritis based on a 28-joint assessment. DAS28-4 (CRP) was calculated from number of painful joints out of 28 joints (TJC28) and number of swollen joints out of 28 joints (SJC28), CRP (mg/L) and PtGA on a 100 mm VAS (VAS: scores ranging from 0 mm \[very well\] to 100 mm \[worst\], higher scores indicated worse health condition). Total DAS28-4 (CRP) score range: 0 to 9.4, higher score indicated more disease activity. DAS28-4 (CRP) \<= 3.2 indicates low disease activity and \> 3.2 to \<=5.1 indicates moderate disease activity, \>5.1 indicates high disease activity, and DAS28-4 (CRP) \< 2.6 indicates remission. DAS28-4 (CRP) = 0.56\*sqrt(TJC28) + 0.28\*sqrt(SJC28) + 0.36\*ln(CRP in mg/L +1) + 0.014\*PtGA in mm+ 0.96.

ACR20 response is a \>= 20% improvement in TJC (28) and SJC (28) and \>=20% improvement in 3 of the 5 remaining ACR-core criteria: 1) PGA of arthritis, 2) PtGA of arthritis, 3) participant's assessment of arthritis pain, 4) participant's assessment of functional disability by HAQ-DI, and 5) CRP (mg/L) at each visit. PGA: physician's global assessment of arthritis on VAS, 0 (very well) to 100 mm (worst arthritis), higher scores=worse condition. PtGA: participant's global assessment of arthritis on VAS, 0 mm (very well) to 100 mm (worst arthritis condition), higher scores = worse condition. Participant's assessment of arthritis pain: assessed on VAS, 0 mm (no pain) to 100 mm (most severe pain), higher score = more pain. HAQ-DI: functional disability evaluation, score: 0 (no difficulty) to 3 (unable to do), higher score=more disability.

ACR50 response is a \>= 50% improvement in TJC (28) and SJC (28) and \>=50% improvement in 3 of the 5 remaining ACR-core criteria: 1) PGA of arthritis, 2) PtGA of arthritis, 3) participant's assessment of arthritis pain, 4) participant's assessment of functional disability by HAQ-DI, and 5) CRP (mg/L) at each visit. PGA: physician's global assessment of arthritis on VAS, 0 (very well) to 100 mm (worst arthritis), higher scores=worse condition. PtGA: participant's global assessment of arthritis on VAS, 0 mm (very well) to 100 mm (worst arthritis condition), higher scores = worse condition. Participant's assessment of arthritis pain: assessed on VAS, 0 mm (no pain) to 100 mm (most severe pain), higher score = more pain. HAQ-DI: functional disability evaluation, score: 0 (no difficulty) to 3 (unable to do), higher score=more disability.

ACR70 response is a \>= 70% improvement in TJC (28) and SJC (28) and \>=70% improvement in 3 of the 5 remaining ACR-core criteria: 1) PGA of arthritis, 2) PtGA of arthritis, 3) participant's assessment of arthritis pain, 4) participant's assessment of functional disability by HAQ-DI, and 5) CRP (mg/L) at each visit. PGA: physician's global assessment of arthritis on VAS, 0 (very well) to 100 mm (worst arthritis), higher scores=worse condition. PtGA: participant's global assessment of arthritis on VAS, 0 mm (very well) to 100 mm (worst arthritis condition), higher scores = worse condition. Participant's assessment of arthritis pain: assessed on VAS, 0 mm (no pain) to 100 mm (most severe pain), higher score = more pain. HAQ-DI: functional disability evaluation, score: 0 (no difficulty) to 3 (unable to do), higher score=more disability.

HAQ-DI assesses the degree of difficulty a participant has experienced during the past week in 8 domains of daily living activities: dressing/grooming; arising; eating; walking; reach; grip; hygiene; and other activities. There were total of 30 items distributed in these 8 domains. Each item was scored on a 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 (least difficulty) and 3 (extreme difficulty), where higher scores indicate more difficulty while performing daily living activities.

Pfizer

Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. SAS included all participants randomized in the study and received at least one dose of the randomized investigational drug. Total 153 deaths of which 152 were adjudicated and 1 occurred after the participant discontinued from the study.

Participants received tofacitinib 5 milligram (mg) oral tablet twice daily (BID) up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.

Tofacitinib 5 mg BID

Participants received tofacitinib 10 mg oral tablets (two tablets of 5 mg each) BID up to 72 months. Dose was reduced to tofacitinib 5 mg BID on or after 19 February 2019 as per Study Protocol Amendment 8. Participants were followed up for at least 28 days after last dose of study drug.

Tofacitinib 10 mg BID

In the United States (US), Puerto Rico and Canada, participants randomized to tumor necrosis factor inhibitor (TNFi) arm received adalimumab 40 mg every other week (QOW) by subcutaneous (SC) injection and in all other countries, participants randomized to TNFi arm received etanercept 50 mg once weekly by SC injection up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.

TNFi

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race

Race/Ethnicity, Customized

Safety Analysis Set (SAS) included all participants who were randomized in the study and received at least one dose of the randomized investigational drug (tofacitinib or TNFi).

Pfizer ClinicalTrials.gov Call Center

Tofacitinib 10 mg BID versus Tofacitinib 5 mg BID

All participants who received treatment in either tofacitinib 5 mg or tofacitinib 10 mg group BID up to 72 months. Participants were followed up for at least 28 days after last dose of study drug.

All Tofacitinib

SAS included all participants who were randomized in the study and received at least one dose of the randomized investigational drug (tofacitinib or TNFi).

Incidence Rate of Adjudicated Malignancies Excluding Non-melanoma Skin Cancers (NMSC)

Incidence Rate of Adjudicated Major Adverse Cardiovascular Events (MACE)

Incidence Rate of Non-fatal Stroke

Incidence Rate of Non-fatal Myocardial Infarction

Incidence Rate of Adjudicated Opportunistic Infection Events Including Tuberculosis

Incidence Rate of Adjudicated Hepatic Events

Incidence Rate of Adjudicated Cardiovascular Events Other Than Major Adverse Cardiovascular Events (MACE)

SAEs

Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

Analysis population included all participants from SAS with an abnormal baseline with at least one observation of the given laboratory test while on study treatment or during lag time.

Number of Participants With Clinically Significant Abnormal Laboratory Parameters

Deaths-Total

Deaths - Infections

Deaths - Cardiovascular Events

Deaths - Malignancies

Deaths - Other Causes

Incidence Rate of Adjudicated All-Cause Deaths

Permanent discontinuation: AE

Temporary discontinuation: AEs

Permanent discontinuation: treatment related AE

Temporary discontinuation: treatment related AE

Permanent discontinuation: COVID-19 Related AEs

Temporary discontinuation: COVID-19 Related AEs

Permanent discontinuation: Herpes Zoster

Temporary discontinuation: Herpes Zoster

Number of Participants With Reasons For Permanent or Temporary Discontinuation of Study Medication

Change at Month 2

Change at Month 3

Change at Month 6

Change at Month 9

Change at Month 12

Change at Month 15

Change at Month 18

Change at Month 21

Change at Month 24

Change at Month 27

Change at Month 30

Change at Month 33

Change at Month 36

Change at Month 39

Change at Month 42

Change at Month 45

Change at Month 48

Change at Month 51

Change at Month 54

Change at Month 57

Change at Month 60

Change at Month 63

Full Analysis Set (FAS): all participants randomized and received at least one dose of drug. Mixed model for repeated measures used without imputation for missing values. Analyses included data while participants were receiving drug. Only visits with N \> 50 participants in each treatment group included in analyses. Number of Participants Analyzed: number of participants included in mixed model for repeated measures. Number Analyzed: number of participants evaluable for each specified time point.

Change From Baseline in Disease Activity Score 28-4 (DAS28-4) C-reactive Protein (CRP) at Month 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60 and 63

Change at month 27

FAS: all participants randomized and received at least one dose of drug. Mixed model for repeated measures used without imputation for missing values. Analyses included data while participants were receiving drug. Only visits with N \> 50 participants in each treatment group included in analyses. Number of Participants Analyzed: number of participants included in mixed model for repeated measures. Number Analyzed: number of participants evaluable for each specified time point.

Change From Baseline in Simplified Disease Activity Index (SDAI) Score at Month 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60 and 63

Change From Baseline in Clinical Disease Activity Index (CDAI) Score at Month 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60 and 63

Month 2

Month 3

Month 6

Month 9

Month 12

Month 15

Month 18

Month 21

Month 24

Month 27

Month 30

Month 33

Month 36

Month 39

Month 42

Month 45

Month 48

Month 51

Month 54

Month 57

Month 60

Month 63

Month 66

Month 69

Month 72

FAS included all participants randomized in study and received at least one dose of randomized investigational drug. Analyses included data while participants were receiving the study drug. 'Number Analyzed' signifies number of participants evaluable for each specified time point. Last Observation Carried Forward (LOCF) applied for missing components and composite binary outcome was calculated. The percentages were calculated using numbers of participants evaluable at each visit as denominators.

Percentage of Participants Who Achieved Observed American College of Rheumatology-European League Against Rheumatism (ACR-EULAR) Boolean Remission Criteria

FAS included all participants randomized in the study and received at least one dose of investigational drug. Analyses included the data while the participants were receiving the study drug. Here, 'Number Analyzed' signifies number of participants evaluable for each specified time point. LOCF was applied for missing components, and then composite binary outcome was calculated. The percentages were calculated using the numbers of participants evaluable at each visit as the denominators.

Percentage of Participants With Simplified Disease Activity Index (SDAI) Less Than or Equal to (<=) 3.3

Percentage of Participants With Clinical Disease Activity Index (CDAI) <=2.8

Percentage of Participants With Simplified Disease Activity Index (SDAI) <=11

Percentage of Participants With Clinical Disease Activity Index (CDAI) <=10

Percentage of Participants With Disease Activity Score 28-4 (DAS28-4) C-reactive Protein (CRP) <=3.2

FAS included all participants randomized in the study and received at least one dose of investigational drug. Analyses included the data while the participants were receiving the study drug. Here, 'Number Analyzed' signifies number of participants evaluable for each specified time point. LOCF was applied for missing components, and then composite binary outcome was calculated.

Number of Participants With an American College of Rheumatology 20 Percent (%) (ACR20) Response

Number of Participants With an American College of Rheumatology 50% (ACR50) Response

Number of Participants With an American College of Rheumatology 70% (ACR70) Response

Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Months 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60 and 63

Overall Study

Nutritional and Metabolic Diseases

Infections

Rare Diseases

Obesity

Spondylitis

Arthritis, Psoriatic

Spondylarthritis

Spondylitis, Ankylosing

Communicable Diseases

Bone Diseases

Bone Diseases, Infectious

Spinal Diseases

Spondylarthropathies

Psoriasis

Skin Diseases

Skin Diseases, Papulosquamous

Axial Spondyloarthritis

Ankylosis

Spondylarthropathy

Dermatologic Agents

Infliximab

Patients with Rheumatoid Artritis, Psoriatic Arthritis, Anchylosing Spondylitis starting treament with infliximab or adalimumab

Karen B Lauridsen, MD

Lene Dreyer, MD, Prof.

The aim of the study is to explore whether the influence of gender, tobacco smoking and obesity on treatment response in tumor necrosis factor inhibitors (TNFIs) can be explained by high degree of inflammation, human leucocyte antigen (HLA) type, autoantibodies, TNF and TNFI concentration and presence of ADA.

Tumor necrosis factor inhibitors (TNFIs) have been uses with success since 1999 in Denmark in treatment of various inflammatory diseases, eg. rheumatoid arthritis (RA), Chrohn's disease, psoriasis, psoriatic arthritis (PsA) and ankylosing spondylitis (AS).

TNFIs block a central cytokine in the inflammatory process, tumor necrosis factor (TNF).

Because the drugs are large proteins, they are prone to trigger an immune response and elicit anti-drug antibodies(ADA).

Epidemiologic studies have revealed that groups of patients (women, tobacco smokers, obese patients) with inflammatory rheumatic diseases have a lower response to TNFIs. The reasons for this are not fully elucidated. The hypothesis is that immunogenicity and changed pharmacokinetic of TNFI are causes of the inferior response.

The investigators will carry out a prospective clinical studies of 120 arthritis patients (RA, PsA and AS) initiating treatment with adalimumab or infliximab. The patients will be followed for 12 months and will be registered in DANBIO as normal praxis. Blood samples will be collected at baseline, 2, 4 and 12 months or at termination of the treatment.

Genotypes, autoantibodies, inflammation markers, TNFI and ADA will be measured.

The aim of the study is to explore:

A: If differences between men and women with respect to different markers of inflammation, human leucocyte antigen (HLA), autoantibodies, TNFI concentration and presence of ADAs can explain the lower response and adherence to the treatment among women.

B: If differences between smokers and non-smokers with respect to different markers of inflammation, HLA, autoantibodies, TNFI concentration and presence of ADAs can explain the lower response and adherence to the treatment among patients with arthritis who smoke tobacco.

C: If differences between obese and normal weight patients with respect to different markers of inflammation, HLA, autoantibodies, TNFI concentration and presence of ADAs can explain the lower response and adherence to the treatment.

The study will contribute with new knowledge, which hopefully can make the treatment more personalized and efficient.

EDTA Whole Blood EDTA-plasma, EDTA-buffy coat, serum.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Safety Study Of Tofacitinib Versus Tumor Necrosis Factor (TNF) Inhibitor In Subjects With Rheumatoid Arthritis	NCT02092467	Arthritis, Rheu...	tofacitinib tofacitinib adalimumab etanercept	50 Years -	Pfizer
Safety Study Of Tofacitinib Versus Tumor Necrosis Factor (TNF) Inhibitor In Subjects With Rheumatoid Arthritis	NCT02092467	Arthritis, Rheu...	tofacitinib tofacitinib adalimumab etanercept	50 Years -	Pfizer
Characterization of Immunogenicity of TNF Inhibitors in Arthritis Patients With Poorer Treatment Response.	NCT04731831	Arthritis, Rheu... Arthritis, Psor... Spondylitis, An...		18 Years -	Aalborg University Hospital
Safety Study Of Tofacitinib Versus Tumor Necrosis Factor (TNF) Inhibitor In Subjects With Rheumatoid Arthritis	NCT02092467	Arthritis, Rheu...	tofacitinib tofacitinib adalimumab etanercept	50 Years -	Pfizer
Effectiveness and Safety of Yisaipu Combined With Tripterygium Wilfordii for Active RA	NCT03589833	Arthritis, Rheu...	Tripterygium Wi... Methotrexate Yisaipu	18 Years - 65 Years	Peking Union Medical College Hospital
Assessing the Suitability of an Imaging Probe for Use in Clinical Cell and Gene Therapy Trials in Cancer and Rheumatoid Arthritis	NCT00185848	Brain Cancer Arthritis, Rheu... Central Nervous... Glioma	[18F]FHBG	18 Years -	Stanford University
A Study to Learn About the Study Medicine Called Infliximab (Genetical Recombination)[Infliximab Biosimilar 3] in People With Rheumatoid Arthritis, Ulcerative Colitis, Crohn's Disease, or Psoriasis	NCT05796245	Arthritis, Rheu... Colitis, Ulcera... Crohn Disease Psoriasis		15 Years -	Pfizer
Study of CP-690,550 Versus Placebo In Rheumatoid Arthritis Patients On Background Methotrexate With Inadequate Response To Tumor Necrosis Factor (TNF) Inhibitors	NCT00960440	Arthritis, Rheu...	CP-690,550 CP-690,550 Placebo CP-690,550 Placebo CP-690,550	18 Years -	Pfizer
Study of CP-690,550 Versus Placebo In Rheumatoid Arthritis Patients On Background Methotrexate With Inadequate Response To Tumor Necrosis Factor (TNF) Inhibitors	NCT00960440	Arthritis, Rheu...	CP-690,550 CP-690,550 Placebo CP-690,550 Placebo CP-690,550	18 Years -	Pfizer

Spots Global Cancer Trial Database for arthritis, rheumatoid