What is the effectiveness of mycophenolate mofetil vs azathioprin on progression of rheumatoid arthritis related interstitial lung disease?

Study setting will be outpatient rheumatology clinic, Teaching hospital, Karapitiya

Participants will be subject to base line screening tests including pulmonary function test (Forced vital capacity (FVC) and carbon monoxide diffusion capacity (DLCO)) and high resolution computerized tomography chest (HRCT) to identify the radiological pattern and to assess the extent of lung fibrosis.

Following basic investigations, participants will be subject to stratified randomization based on gender, predominant HRCT pattern, and lung disease severity.

Permuted block design will be applied to each stratum for 1:1 allocation of two groups.

Route of drug administration will be oral

Mycophenolate mofetil (MMF) treatment group will receive a MMF 250mg bd dosage initially and will be titrated up to 2g/daily or maximum tolerating dose over a period of eight weeks.

Azathioprine treatment group will be given azathioprine 50mg daily at the beginning, increasing up to 2mg/kg or maximum tolerating dose over an eight weeks period.

Both groups will be given prednisolone 0.5mg/kg up to a maximum dose of 25mg for the initial three months period which will be gradually tailed off over a three month period.

This is an open label study. Therefore no one will be blinded.

1. Patients above 18 years of age

2. Both male and female

3. Patients who full fill the American College of Rheumatology (ACR) /European League Against Rheumatism Collaborative initiative (ACR /EULAR) criteria for the diagnosis of rheumatoid arthritis.

4. Patients with interstitial lung disease, which are diagnosed either based on surgical lung biopsy or radiologically with use of HRCT.

5. Patients with abnormal diffusing capacity for carbon monoxide (DLCO) and Forced vital capacity (FVC) <85% predicted.

6. Low disease activity or remission of arthritis, based on disease activity score calculated by using Disease Activity (DAS 28), without treatment of methotrexate or leflunomide three months prior to the screening

1. Prior use of oral MMF for more than 4 weeks.

2. Patients with clinical evidence of interstitial lung disease, having other connective tissue disorders other than rheumatoid arthritis

3. Patients with significant pulmonary pathology on CXR or HRCT, other than interstitial lung disease (eg. lung mass or evidence of active or chronic pulmonary infection).

4. Patients with pulmonary hypertension requiring specific treatment

5. patients with evidence of acute infection either in lung or anywhere of the body, whose management would be compromised by either azathioprine or MMF

6. Patients who are having contraindications or allergic reactions to MMF or azathioprine on previous exposure.

7. History of persistent leukopenia (white blood cell count < 4000/mm3) or thrombocytopenia (platelet count<100)

8. Pregnancy (documented by urine pregnancy test) and breast feeding

9. Smoking of cigars, pipes or cigarettes during the past 6 months.