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Rheumatoid arthritis : Biological DMARDs
- 1. Dr. Sruthi N. RHEUMATOIDARTHRITIS MANAGEMENT BIOLOGICAL DMARDS
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- 3. DMARDs: Classification Conventional DMARDs BiologicalDMARDs Biological originals Biosimilars Target specific DMARDs
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- 6. Biological DMARDs •T cellinhibitor: Abatacept •B cell inhibitor: Rituximab •Anti IL-6:Tocilizumab •TNF-alpha inhibitors :Adalimumab, Certolizumab, Etanercept, Golimumab, Infliximab •IL-1 R inhibitors: Anakinra, Canakinumab, Rilonacept
- 7. Biological DMARDs •IL-12&23 inhibitor:Ustekinumab •IL-17 A inhibitor: Secukinumab •B lymphocyte stimulator inhibitor : Belimumab Target specific DMARD( tsDMARD): Tofacitinib
- 8. Abatacept Co stimulation modulator,endogenous CTLA-4
- 9. Dose:<60kg :500mg,60- 100:750mg.>100:1000mg(IV infusions) Induction:D0,W2,W4,monthly maintenance Indications Mod-severeRA , other rheumatic diseases, PsA Pharmacokinetics t half: 13-16 days Adverse effects Risk of infections, hypersensitivity, lymphoma, Abatacept antibody Live vaccines avoided up to 3 months
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- 11. Dose:1000mg IV infusions2 infusions separated by 2 weeks, maintenance:6-9months Indications Mod-severe RA Pre treatment Acetaminophen, Antihistamines, Glucocorticoides Adverse effects Risk of infections, Fatal mucocutaneous reactions, rashes, Cytopenias
- 12. Tocilizumab Humanized Binds to soluble& membrane bound IL-6
- 13. Dose:4mg/kg IV increaseup to 8mg/kg not >800mg per infusion Every week Indications Mod-severe RA ,SJIA(2years) PK Dose dependent t half, Increase CYP450 Adverse effects Risk of infections, HTN, headache, Increase liver enzymes, decrease platelet count,Neutropenia, GI perforations, lipid monitoring
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- 15. Adalimumab IgG1 anti TNFalpha Dose:40 mg s/c Every other week Indications Mod-severe RA ,JIA, Psoriasis, Ulcerative colitis, Chrons disease PK t half: 10-20 days
- 16. Certolizumab Humanized Anibody Fabfragment Dose:400 mg at week 2&4 200 mg every other week or 400mg every 4 week Indications Mod-severe RA , Psoriasis, AS, Crohn’s disease PK t half: 14 days
- 17. Etanercept Recombinant fusion protein Dose:s/c 25mg twice weekly or 50mg weekly Indications Mod-severe RA , Psoriasis, AS, Juvenile chronic arthritis PK t half: 4.5 days
- 18. Golimumab Human monoclonal antibody Dose:s/c 50mg Every 4 weeks Indications Mod-severe RA , Psoriasis, AS, Mod-severe ulcerative colitis PK t half: 14 days
- 19. Infliximab Chimeric monoclonal antibody Dose:3-5mg/kg every 8 weeks(3-10mg/kg) Induction:0,2&6 weeks Maintenance every 8 weeks Indications Mod-severe RA , Psoriasis, AS, IBD PK t half: 9-12 days
- 20. Adverse effects ofTNF-alpha inhibitors •Risk of infections • Increase chance of skin cancers •Alopecia • Hypertrichosis •Erosive lichen planus •Cutaneous pseudo lymphoma
- 21. IL-I inhibitors Drug MOADose Indications A/E Anakinra Oldest, Not used s/c 100mg Mod to severe RA,CAPS Injection site reaction, Infections, headache, abdominal pain, transient neutropenia Canakinumab Against IL 1beta s/c SJIA,CAPS Rilonacept Against IL 1beta and 1 alpha s/c CAPS
- 22. USTEKINUMAB SECUKINUMAB MOA:IL-12 &23 antagonist S/croute Indications: RA, PsA, Chrons, Plaque psoariasis A/E:Infections,Post. leukoencephalopathy MOA:IL 17 A receptor S/c route Indications: mod-severe plaque, PsA, AS A/E: Infections, Nasopharyngitis, exacerbate crohns
- 23. Belimumab B lymphocyte stimulation(BLyS) IV infusion 10mg/kg W0,W2,W6 Sero positive SLE A/E:Risk of infection, Depression
- 24. Tofacitinib Target specific DMARDS JAK3/JAK1 Differentiation& proliferation inhibited Indications: Allograft rejection, mod to severe RA, PsA, Psoriasis, JIA A/E:Risk of infections, neutropenia/anemia
- 25. Management Guidelines…… EULAR guidelines First lineMethotrexate (short term glucocorticoides) Conventional DMARDs combinations bDMARDs
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