Major Adverse Cardiovascular Events (MACE) in Rheumatoid Arthritis Patient With Moderate to Severe Disease Activity Treated With Tofacitinib and Statins vs TNF Inhibitors: TOFSTAT CLINICAL TRIAL

This study is a prospective non randomized Clinical Trial Phase-4 aimed at observing the incidence of MACE in RA patients who have moderate to severe disease activity (as determined by the DAS-28 score) and one or more cardiovascular disease (CVD) risks. The patients included in the study will have non-responsiveness to standard cDMARDs treatment and will be prescribed tofacitinib 5 mg twice daily along with statins 20 mg daily as risk modification versus TNF Inhibitor as standard treatment will be the control group.

METHODOLOGY

* Initial Assessment:

* Baseline evaluation including DAS-28 score, lipid profile, and assessment of CVD risk factors (hypertension, diabetes, smoking, cholesterol levels, etc.).
* Recruitment of patients based on inclusion and exclusion criteria.
* Intervention:

* In one group tofacitinib (5 mg twice daily) and statins (atorvastatin 20 mg daily) will be added to the treatment regimen of the patients.
* In control group TNF inhibitor will be added to the treatment regimen of the patients as part of standard treatment.
* Patients will be followed up monthly for a period of 6 months.
* Monthly assessments during follow up: Lipid profile Total cholesterol, LDL, HDL, triglycerides, DAS-28 score, Recording of any CVD events (MACE), Monitoring of any other related complications.
* Tofacitinib Discontinuation:

o If a patient experiences a CVD event, tofacitinib will be stopped and documented.
* Follow up:

* Monthly visits for a 6 month, during which patient progress and any adverse events will be recorded.
* If a MACE occurs, treatment with tofacitinib will be discontinued, and the event will be thoroughly documented.

• Tofacitinib 5 MG (Drug), also known as statins: * In one group tofacitinib (5 mg twice daily) and statins (atorvastatin 20 mg daily) will be added to the treatment regimen of the patients. * In control group TNF inhibitor will be added to the treatment regimen of the patients as part of standard treatment. * Patients will be followed up monthly for a period of 6 months. * Monthly assessments during follow up will include Lipid profile Total cholesterol, LDL, HDL, triglycerides. DAS-28 score. Recording of any CVD events (MACE). Monitoring of any other related complications.

Primary outcomes

• Major Adverse Cardiovascular Event [6 months]: incidence of MACE in Rheumatoid Arthritis patients with moderate to high disease activity and with one or more cardiovascular disease risks, which are non-responsive to standard conventional DMARDs (cDMARDs) treatment and are prescribed Tofacitinib 5 mg twice daily along with statin 20 mg daily versus TNF Inhibitors.
• Compare Incidence of MACE in two group [6 months]: o The study aim to compare MACE in RA patients treated with tofacitinib and statin versus TNF inhibitors.

Secondary outcomes

• effectiveness of tofacitinib in controlling disease activity [6 months]: o To evaluate the effectiveness of tofacitinib in reducing RA disease activity as measured by the DAS-28 score.
• lipid profile [6 months]: o To assess the impact of statins on lipid profile in RA patients on tofacitinib

Sex: All, ages: 50 Years to 85 Years

Inclusion Criteria:

* • RA diagnosis with moderate to severe disease activity, based on DAS-28 despite on > 2 conventional DMARDs.

  * One or more CVD risk factors, such as hypertension, diabetes, smoking, high cholesterol, etc.
  * Age 50 or older.

Exclusion Criteria:

* Known contraindications to statins.

  * History of major adverse CV events (e.g., recent myocardial infarction or stroke).
  * Pregnancy or breastfeeding.

• Masooma Hashmat, FCPS, Principal investigator, Shaikh Zayed Hospital, Lahore
• Aflak Rasheed, FCPS, Study director, Shaikh Zayed Hospital, Lahore
• Maira Khalil, MBBS, Study chair, Shaikh Zayed Hospital, Lahore