This document provides an overview of the management of rheumatoid arthritis (RA). It discusses the etiology and pathology of RA and describes the diagnostic criteria. It then outlines various treatment approaches for RA including physical therapies, medications like NSAIDs, glucocorticoids, DMARDs, and biologics. Newer targeted biologic therapies that inhibit cytokines like TNF-α, IL-1, IL-6 are discussed. The goals of RA treatment and factors influencing treatment choice are also summarized.

1. MANAGEMENT OF RHEUMATOID ARTHRITIS Dr.Harmanjit Singh Department of Pharmacology Govt Medical College,Patiala.

6. Diagnosis of rheumatoid arthritis Morning stiffness  1h Three or more joints involved Arthritis of hand joints Symmetric arthritis Rheumatoid nodules ( over bony prominence , extensor surfaces) Rheumatoid factor (positive < 5% normal subjects) Radiographic changes (must show erosion/decalcification) Present for  6wk Any 4 of the following must be present to allow diagnosis of RA ( Patients with 2 or more clinical diagnoses are not excluded )

11. Goals of therapy Alleviate pain Preservation of function Control disease activity Maximize quality of life Slow progression/rate of joint damage

39. TNf-  blocking agents More effective in combination with methotrexate Drug Primary action ROA Usual dose Half life Infliximab Chimeric anti TNF- Ab I/V inj. 3 mg/kg at 0,2,6 wks, then 8 wkly. Gradual ↑ to 10 mg/kg if incomplete response 9 days Etanercept Soluble TNF fusion protein, Binds TNF- α & β S/C inj. 25 mg twice/wk or 50 mg once/wk 4 days Adalimumab Human anti- TNF- α Ab S/C inj. 40 mg every 2 nd wk 2 wks

41. IL-1R antagonists: ANAKINRA

46. BIOLOGICS : FUNCTION AT A GLANCE

49. FUTURE PROSPECTIVES compound MOA Development phase USA EU TNF inhibitors CDP-870 Anti-TNF Ab fragment III III Pegsunercept Pegylated soluble TNF R type 1 II ISIS-104838 TNF-  antisense inhibitors II AGIX4207 TNF inhibitor (oral) II II IL based therapies Atlizumab Humanized anti-IL6 R monoclonal Ab II I HuMAX-IL-15/AMG-714 Anti-IL-15 monoclonal Ab II II ABT-874/J-695 Anti-IL-12 monoclonal Ab II II

50. FUTURE PROSPECTIVES Compound MOA Development phase USA EU Cell adhesion molecule inhibitors Natalizumab Humanized monoclonal Ab II II Co-stimulation inhs CTLA4-Ig CD27/B7 pathway inhibitor III Alefacept CD2 antagonist II

51. FUTURE PROSPECTIVES Immunoadsorption Apheresis – new technique used in pts who are not responding to drug therepy Compound MOA Development phase USA EU Other therapies CCI-779/ Temsirolimus Cell cycle inhibitor II Belimumab Ab against B cell stimulator protein II AT-001/dnaJp1 Heat shock derived protein II