Disease modifying anti rheumatoid drugs in rheumatoid arhtritis

Disease modifying anti rheumatoid drugs in rheumatoid arhtritis by Dr. Bipul Borthakur

1. DISEASE MODIFYING ANTI RHEUMATOID DRUGS IN RHEUMATOID ARHTRITIS DR. B. BORTHAKUR (PROF.) DEPT.OF ORTHOPAEDICS, SMCH

2. WHAT IS RHEUMATOID ARTHRITIS? LONG LASTING AUTOIMMUNE DISORDER PRIMARILY AFFECTS JOINTS RESULT IN WARM, SWOLLEN & PAINFUL JOINTS WRISTS & HANDS ARE MORE COMMONLY INVOLVED CAUSE IS NOT CLEAR BUT BILIEVED TO INVOLVE GENETIC & ENVIRONMENTAL FACTORS

3. DMARDs TO BE DESIGNATED A DMARD, A DRUG MUST CHANGE THE COURSE OF RA FOR ATLEAST 1 YEAR AS EVIDENCED BY- SUSTAINED IMPROVEMENT IN PHYSICAL FUNCTION DECREASED INFLAMMATORY SYNOVITIS SLOWING OR PREVENTION OF STRUCTURAL JOINT DAMAGE

4. TYPES CONVENTIONAL METHOTREXATE SULPHASALAZINE ANTIMALARIAL (HCQ, CQ) LEFLUNOMIDE MINOCYCLINE CYCLOSPORINE GOLD (SODIUM AUROTHIOMALATE, AURANOFIN) MISCELLANEOUS (LEVAMISOLE, MYCOPHENOLATE MOFETIL, TACROLIMUS) BIOLOGICAL INFLIXIMAB ETANERCEPT ADALIMUMAB GOLIMUMAB CERTOLIZUMAB ABATACEPT RITUXIMAB TOCILIZUMAB SECUKINUMAB BELIMUMAB

5. CONVENTIONAL DMARDs METHOTREXATE THERAPEUTIC DOSE (7.5-25) mg ORALLY WEEKLY STARTING DOSE - (7.5-15) mg WEEKLY 2.5 mg INCREMENTS AT INTERVAL OF 4 WEEKS BENEFICIAL EFFECT APPRECIABLE IN 1-2 MONTHS & PEAKS AT 6 MONTHS

6. SIDE EFFECTS ANOREXIA & NAUSEA (WITHIN 24HRS) – M/C DIARRHOEA ORAL ULCER STOMATITIS ELEVATED LIVER ENZYMES HEPATIC FIBROSIS SKIN RASHES MTX NODULOSIS, MTX PNEUMONITIS RISK OF OPPORTUNISTIC INFECTION

7. TO REDUCE GI SIDE EFFECTS FOLIC ACID (5-15) mg / WEEK ONDANSETRON CONTRAINDICATIONS PREGNANCY RENAL INSUFFICIENCY LIVER DISEASE

8. BASE LINE EVALUATION BLOOD COUNT, S. CREATININE, LFT, CXR SCREENING FOR HEP B, HEP C, HIV UPT MONITORING BLOOD COUNTS & LFT – 4-8 WEEKLY S. CREATININE – 6 MONTHLY

9. SULPHASALAZINE POORLY ABSORBED SULFONAMIDE SPLITS INTO 5-ASA & SULPHAPYRIDINE IN COLON SULPHAPYRIDINE – EFFICACY FOR RA 5-ASA – EFFICACY FOR ULCERATIVE COLITIS

10. DOSE STARTED AT 500 mg / DAY INCREASED BY 500 mg/ WEEKLY TO (2-3) g/ DAY SIDE EFFECTS NAUSEA, ABNOMINAL PAIN SKIN RASHES CNS DISTURBANCES REVERSIBLE OLIGOSPERMIA DISCOLORATION OF URINE & SWEAT BLOOD DYSCRASIAS ELEVATED LIVER ENZYMES

11. MONITORING BLOOD COUNTS & LFT EVERY 4 WEEKS FOR 3 MONTHS THEN EVERY 3 MONTHS TILL 1 YR 6 MONTHLY DURING 2 ND YR (IF RESULTS NORMAL IN 1 ST YR) THEREAFTER MONITORING DISCONTINUED

12. ANTI-MALARIALS USED EITHER IN MILD RA OR IN COMBINATION FOR TREATMENT OF RA BOTH HCQ & CQ EQUALLY EFFICACIOUS HCQ PREFFERED AS OCULAR TOXICITY RARE TIME OF ONSET OF BENEFIT – (1-6) MONTHS

13. DOSE CQ 5 mg/kg/ DAY HCQ 6.5 mg/kg/ DAY OCULAR SCREENING BASELINE SCREENING WITHIN 1 ST YR OF HCQ USE ANNUAL CHECKUP AFTER 5 YRS SIDE EFFECTS NAUSEA, INDIGESTION, PRURITUS, SKIN RASHES, HYPERPIGMENTATION, HYPOGLYCEMIA

14. LEFLUNAMIDE HAS A GOOD SAFETY PROFILE SAFE IN CKD DOSE STARTED AT 20 mg / DAY ORALLY BENEFICIAL EFFECTS APPEAR AFTER 4-6 WEEKS SIDE EFFECTS LIVER TOXICITY, NAUSEA, DIARRHOEA, ALOPECIA, WT LOSS & OCCASSIONALLY HTN

15. CONTRAINDICATIONS PREGNANCY (TERATOGENIC IN ANIMAL STUDY) IN MALES CONTEMPLATING FATHERING A CHILD MONITORING – SAME AS MTX CHOLESTYRAMINE 8 mg TDS FOR 11 DAYS IN SEVERE LIVER TOXICITY BONE MARROW TOXICITY

16. MINOCYCLINE USED IN EARLY & MILD RA SEMISYNTHETIC DERIVATIVE OF TETRACYCLINE HAS IMMUNOMODULATORY AND ANTIINFLAMMATORY PROPERTIES DOSE – 100 mg BD SIDE EFFECTS (GI SIDE EFFECTS, DIZZINESS, RASH, HEADACHE) COMMON PERSISTENT SKIN & MUCOSAL HYPERPIGMENTATION, LUPUS LIKE SYNDROME ACUTE LIVER INJURY

17. CYCLOSPORINE RECOMMENDED FOR PTS REFRACTORY TO MTX DOSE – (3-5) mg/kg/ DAY MONITORING CBC, LIVER ENZYMES, S. CREAT – WEEKLY UNTILL STABLE DOSE REACHED THEN MONTHLY SIDE EFFECTS (RISE IN S. CREAT & BP) COMMON HYPERKALAEMIA, GUM HYPERPLASIA, HYPERTRICHOSIS, HEPATOTOXICITY S. CREAT > 30% OVER BASELINE – STOP DRUG

18. G OLD SALTS 2 TYPES WATER SOLUBLE – THIOLATE FAT SOLUBLE – PHOSPHINE ELIMINATED VERY SLOWLY DOSE (INJECTABLE) 10 mg STARTED IM 50 mg WEEKLY UNTILL CUMMULATIVE DOSE OF 1g IF NO IMPROVEMENT – STOPPED

19. IF SIGNIFICANT IMPROVEMENT ONCE IN A FORTNIGHT FOR NEXT 3 MONTHS ONCE IN 3 WEEKS FOR 3 MONTHS CONTINUED MONTHLY DOSE (ORAL) AURANOFINE – (3-6) mg/kg/DAY SIDE EFFECTS SKIN RASHES, ORAL ULCERS, PROTEINURIA, THROMBOCYTOPAENIA, PULMONARY TOXICITY MONITORING BLOOD COUNT & URINE PROTEIN BEFORE EACH INJ FOR 4-8 WEEKS THEN BEFORE EVERY 3 RD OR 4 TH INJ

20. DMARD COMBINATION THERAPY INCREASE EFFICACY OF TREATMENT MULTIPLE DRUGS ACT SYNERGYSTACALLY AT MULTIPLE POINTS TYPES OF COMBINATION STEP UP STEP DOWN PARALLEL

21. ROLE OF VACCINATION BASED ON AGE & RISK EVERY PT SHOULD BE VACCINATED HERPES ZOSTER (LIVE ATTENUATED) HUMAN PAPILLOMA VIRUS HEP B INFLUENZA PNEOMOCOCCUS 4 WEEKS GAP IS ADVISED B/W ZOSTER VACCINATION & COMMENCEMENT OF BIOLOGIC THERAPY

22. BIOLOGICS

23. THANK YOU