BASELINE VARIABLES PREDICTING TREATMENT RESPONSE AT 6 MONTHS IN ADULT RHEUMATOID ARTHRITIS PATIENTS TREATED WITH TOFACITINIB 5MG BID IN A NON-INTERVENTIONAL SETTING (TREAT - RA)
Conditions: Rheumatoid Arthritis
Sponsor: Pfizer

 
 

 
 

 
 

 
 

 
 

 
 

 
 

 

Tofacitinib citrate 
A3921342 NON-INTERVENTIONAL STUDY PROTOCOL 
Version 2.0, 14 January 2020 
 
7. RATIONALE AND BACKGROUND 
Rheumatoid arthritis (RA) is a chronic, autoimmune disease characterized by joint 
inflammation and destruction, leading to a progressive disability and adverse psychological 
effects with severe impact on patients’ quality of life.1 Apart from musculoskeletal 
complications directly related to their rheumatic disease, RA subjects are also at increased 
risk of suffering from co-morbidities such as cardiovascular and infectious diseases, 
osteoporosis, depression and cancer, contributing to the higher mortality rate observed in RA 
patients compared to the general population.2 
The chronic nature of the disease deems necessary the long-term use of medication. Thus, 
RA represents significant health and socioeconomic burdens for the individual subject, 
healthcare systems and society, with indirect costs (productivity loss, absenteeism/disability, 
early retirement) accounting for up to ¾ of total costs for working patients.3 
As there is currently no cure for RA, the target of treatment strategies is to control disease 
activity, alleviate signs and symptoms, maintain physical function, optimize quality of life, 
reduce the rate of joint damage, and, if possible, induce and maintain complete remission.1 
Although there are several effective treatments available nowadays, mainly biologic 
DMARDs, many patients fail to achieve or maintain the desired response and are treated 
sequentially with different drugs leading to increased costs, risk of toxicity and suboptimal 
effectiveness. Therefore, the ambition for personalized treatment has emerged and 
investigation to identify predictive tools of treatment response is a highly active area of 
research.4 
Tofacitinib (CP-690,550) is an oral Janus kinase (JAK) inhibitor that targets inflammation by 
reducing pro-inflammatory cytokine signaling and production.5 
The efficacy and safety evaluation of tofacitinib for the treatment of RA is based on a 
comprehensive clinical development program including six randomized, double blind, 
multicenter phase III studies in adult subjects with active rheumatoid arthritis (RA). In these 
trials tofacitinib consistently reduces signs and symptoms of RA, improves physical function 
and other subject-reported outcomes such as fatigue, pain and health-related aspects of 
quality of life in subjects with moderate to severe RA. Combined with its inhibition of the 
progression of structural damage, the development program has demonstrated tofacitinib as 
an effective targeted synthetic disease-modifying anti-rheumatic drug (DMARD) in treating 
RA.6-11  Long-term extension and Phase 3b/4 post authorization safety studies are aimed to 
demonstrate sustained efficacy and a consistent safety profile as seen in the Phase 2 and 3 
controlled clinical trials. 

However, these trials may have limitations reflecting real world situations. It has been 
estimated that only 21-33% of patients documented in registries, reflecting more accurately 
routine care, would have met eligibility criteria of major trials as they often exclude patients 
with co-morbidities.12 Also treatment of patients in daily clinical practice may vary from the 
strictly regulated schemes followed in clinical trials. Therefore, additional long-term data in 
registries and non-interventional studies of a European population would be helpful to further 
assess treatment outcomes in a real-world setting.  
PFIZER CONFIDENTIAL 
  
29-Jul-2019 Page 9