Rheumatoid arthritis

Pharmacotherapeutics of Rheumatoid Arthritis

1. Dr. V.S.SWATHI ASSISTANT PROFESSOR Rheumatoid Arthritis

2. Definition Rheumatoid arthritis is a long term, progressive and disabling auto immune disease, causes inflammation, swelling, and pain in and around the joints and other body organs

3. Epidemiology In the world, Rheumatoid Arthritis is 1% and annual incidence is 3 cases per 10,000 population In India, it affects about 0.92% of adult population

4. Types Seropositive RA Here there is positive results for Rheumatoid factor(R) and anti cyclic citrullinated peptide(ACCP) Body produces immune reactions to normal tissue Chances of developing RA is four times greater if parents are having RA 80% of people who are having RA are with RF positive Seronegative RA Here there is negative results for Rheumatoid factor(RF) and anti cyclic citrullinated peptide(ACCP) RA is confirmed by other tests Juvenile Idiopathic RA It is common in children younger than age 17 Symptoms may be temporary and lasts for lifetime In severe conditions, it interferes with child growth and development

5. Risk factors Age in between 40-60 Family history of RA Environmental pollution Women Obesity Smoking

6. Etiology Abnormal expression of Human Leukocyte Antigen gene-HLA DR 4 and HLA DRB 1 gene

7. Pathogenesis

8. Clinical Presentation Early stages of disease Pain Stiffness (mostly in morning lasts for 30 minutes to several hours) Swelling In metacarpophalangeal joints of fingers In proximal interphalangeal joints of fingers In interphalangeal joints of thumb In metatarsophalangeal joints In joints of wrist

9. Late stages of disease Boutonniere deformity of thumb Ulnar deviation of metacarpophalangeal joints Swan-neck deformity of fingers Other manifestations Myalgia Fatigue Low grade fever Weight loss Depression

10. Complications Amyloidosis Carpal tunnel syndrome Episcleritis Felty’ s Syndrome Lymphadenopathy Nodules Osteoporosis Pericarditis Pleural and Pericardial effusion Scleritis Vasculitis Sjogren’ s Syndrome Cardiovascular Stroke Cervical myelopathy

11. Diagnosis American Rheumatism Association (ARA) criteria for the diagnosis of Rheumatoid Arthritis Morning stiffness in and around the joints for at least 6 weeks, lasting at least 1 hour before maximal improvement Swelling of 3/ more joints for at least 6 weeks Swelling of the wrist, metacarpophalangeal/ proximal interphalangeal joints for at least 6 weeks Symmetric joint swelling for at least 6 weeks Hand X-ray changes typical of Rheumatoid arthritis that must include erosions/ unequivocal bony decalcification around the joints Rheumatoid subcutaneous nodules Positive rheumatoid factor Interpretation: Presence of at least 4 of these indicators diagnosis of Rheumatoid Arthritis

12. Disease Activity Score (DAS 28) using 28 joints Number of swollen joints out of a total 28 specified joints Number of tender joints out of a total 28 specified joints Erythrocyte sedimentation rate Patient’s interpretation of wellbeing with 0 being at their best and 100 their worst Interpretation: High disease activity: >5.1 Moderate disease activity: 3.2-5.1 Low disease activity: 2.6-3.2 Remission: <2.6

13. Anti cyclic citrullinated peptide antibody (ACCP) Rheumatoid factor Antinuclear antibodies (ANA) Alkaline phosphatise Platelet count Serum albumin Neutrophils

14. Non Pharmacological Treatment Patient education and counselling on risk factors Stopping of alcohol and smoking Rest Occupational therapy Trancutaneous electric nerve stimulator (TENS) Hydrotherapy Surgical interventions like Synovectomy and Arthoplasty

15. Treatment Algorithm

16. Drugs used in treatment of Rheumatoid Arthritis Drug Category Mode of Action Dose Adverse effects Aspirin NSAID Inhibit prostaglandin synthesis 2.6-5.2g/day-PO Angioedema Bronchospasm CNS alteration GI disturbances Renal damage Diclofenac NSAID Inhibit prostaglandin synthesis 150-200mg-PO Abdominal distension Dyspepsia Fluid retention Pruritis Nephrotoxicity Prednisone Corticosteroids Inhibit inflammatory reactions Less than 10mg/day-PO Hypertension Decreased wound healing Hirsutism Weight gain Glaucoma

17. Methyl Prednisolone Corticosteroids Inhibit inflammatory reactions 2-60mg/day-PO Acne Decreased wound healing Diabetes Edema Osteoporosis Methotrexate DMARDs Inhibit cellular proliferation 7.5-15mg/ week-PO/IM Hyperurecemia Ulcerative stomatitis Glossitis Leukopenia Thrombocytopenia Hydroxychloroquine DMARDs Impair complement dependent antigen and antibody reactions 200-300mg- BD- PO Irritability Aplastic anaemia Leukopenia Thrombocytopenia Alopecia Sulfasalazine DMARDs Inhibit leukotriene synthesis and lipoxygenase 500mg-BD-PO Anorexia Gastric distress Nausea Vomiting Headache

18. Leflunamide DMARDs Inhibit proliferation of cells 100mg/day for 3 days-PO then 10-20mg/day Diarrhoea Respiratory infections Alopecia Hypertension Rash Etanercept Biological agents Inactivates Tissue necrotic factor 50mg-weekly-SC Infections Injection site reactions Diarrhoea Rash Pruritis Infliximab Biological agents Inhibits the effective binding of Tissue necrotic factor alpha with its receptors 3m/kg-IV at 0,2,6 weeks then 8 week Development of Anti nuclear antibodies Infection Infusion related reactions Bronchitis Dyspepsia

19. Resources ncbi.nlm.nih.gov/ pmc /articles/PMC5215647/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3516026/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5206883/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4860498/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5051257/