1.       SUMMARY OF THE PROPOSAL

Rheumatoid arthritis (RA) is an autoimmune disease with a global prevalence rate of about 0.8%.¹ Although recent data on the epidemiology of RA in Indian population is lacking but published literature for the last decade have reported a prevalence rate of 0.75%.¹Treatment with Disease-Modifying Anti-Rheumatic drugs (DMARD) has taken a pivotal role in the management of RA. Methotrexate (MTX) is the most commonly prescribed first line DMARD due to its favourable cost-effectiveness profile. Although, published literature has documented various adverse effects of MTX ^2-4 but there is limited data on Indian population regarding the long term adverse effects of low dose therapy. Identification of potential risk factors that might predispose individuals to such adverse effects will provide evidence in this domain in Indian population.

 Therefore, this cross sectional observational study aims to evaluate the hematologic and hepatic adverse effects associated with long term low dose therapy of methotrexate in rheumatoid arthritis patients. This study will be carried out jointly by the departments of Rheumatology and Pharmacology of IPGMER and SSKM hospital for a period of eighteen months. Diagnosed patients of rheumatoid arthritis as per American College of Rheumatology (ACR) criteria attending the rheumatology OPD of this hospital will be screened for subject eligibility criteria. Only those patients who have been taking low dose (≤15 mg/weekly) methotrexate for ≥  2 years will be included in the study and they will be evaluated for adverse effects pertaining to the hepatic and haematological systems. As per the treatment guidelines adopted at the Rheumatology department of this institute RA patients who are on methotrexate therapy undergo routine hemogram (haemoglobin, count and differential count) and liver enzymes- serum alanine transaminase, aspartate transaminase and alkaline phosphatase (ALT, AST, ALP respectively) every 6 months. Clinical and laboratory data of these patients will be recorded in a study specific case record form. Subjects who have abnormal laboratory parameters shall undergo further investigations like ultrasonography as per the standard treatment and diagnostic guidelines adopted for the care of rheumatoid arthritis patients by the attending clinician. Hepatic and haematological adverse reactions will be coded as per the WHO ART (World Health Organization Adverse Drug Reaction Terminology) criteria. The study will be conducted for a period of eighteen months and it is estimated that we shall be able to recruit about 200 patients during the study period. The results shall be compiled and summary statistics will be done. Multiple logistic regression will be done to identify potential risk factors for these adverse effects.