An observational study to evaluate the hematological and hepatic adverse effects of long term low dose methotrexate therapy in Rheumatoid Arthritis patients of India

**1.**SUMMARY OF THE PROPOSAL

Rheumatoid arthritis (RA) is an autoimmune diseasewith a global prevalence rate of about 0.8%.¹ Although recent data on the epidemiologyof RA in Indian population is lacking but published literature for the lastdecade have reported a prevalence rate of 0.75%.1Treatment withDisease-Modifying Anti-Rheumatic drugs (DMARD) has taken a pivotal role in themanagement of RA. Methotrexate (MTX) is the most commonly prescribed first lineDMARD due to its favourable cost-effectiveness profile. Although, publishedliterature has documented various adverse effects of MTX 2-4 butthere is limited data on Indian population regarding the long term adverseeffects of low dose therapy. Identification of potential risk factors thatmight predispose individuals to such adverse effects will provide evidence inthis domain in Indian population.

Therefore, this cross sectional observational studyaims to evaluate the hematologic and hepatic adverse effects associated with longterm low dose therapy of methotrexate in rheumatoid arthritis patients. This studywill be carried out jointly by the departments of Rheumatology and Pharmacologyof IPGMER and SSKM hospital for a period of eighteen months. Diagnosed patientsof rheumatoid arthritis as per American College of Rheumatology (ACR) criteriaattending the rheumatology OPD of this hospital will be screened for subjecteligibility criteria. Only those patients who have been taking low dose (≤15mg/weekly) methotrexate for ≥  2 yearswill be included in the study and they will be evaluated for adverse effects pertainingto the hepatic and haematological systems. As per the treatment guidelinesadopted at the Rheumatology department of this institute RA patients who are onmethotrexate therapy undergo routine hemogram (haemoglobin, count anddifferential count) and liver enzymes- serum alanine transaminase, aspartatetransaminase and alkaline phosphatase (ALT, AST, ALP respectively) every 6months. Clinical and laboratory data of these patients will be recorded in astudy specific case record form. Subjects who have abnormal laboratoryparameters shall undergo further investigations like ultrasonography as per thestandard treatment and diagnostic guidelines adopted for the care of rheumatoidarthritis patients by the attending clinician. Hepatic and haematological adversereactions will be coded as per the WHO ART (World Health Organization AdverseDrug Reaction Terminology) criteria. The study will be conducted for a periodof eighteen months and it is estimated that we shall be able to recruit about 200patients during the study period. The results shall be compiled and summary statistics willbe done. Multiple logistic regression will be done to identify potential riskfactors for these adverse effects.