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Dr. Sruthi N.
RHEUMATOID ARTHRITIS
MANAGEMENT
BIOLOGICAL DMARDS
TOPICS……
Biological DMARDs
Management Guidelines
DMARDs: Classification
Conventional DMARDs
Biological DMARDs
 Biological originals
 Biosimilars
Target specific DMARDs
Pathogenesis
Biological DMARDs
•T cell inhibitor: Abatacept
•B cell inhibitor: Rituximab
•Anti IL-6:Tocilizumab
•TNF-alpha inhibitors :Adalimumab, Certolizumab, Etanercept,
Golimumab, Infliximab
•IL-1 R inhibitors: Anakinra, Canakinumab, Rilonacept
Biological DMARDs
•IL-12&23 inhibitor: Ustekinumab
•IL-17 A inhibitor: Secukinumab
•B lymphocyte stimulator inhibitor : Belimumab
Target specific DMARD( tsDMARD): Tofacitinib
Abatacept
Co stimulation modulator, endogenous CTLA-4
Dose:<60kg :500mg,60-
100:750mg.>100:1000mg(IV
infusions)
Induction:D0,W2,W4,monthly
maintenance
Indications Mod-severe RA , 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
Rituximab
Chimeric
monoclonal
antibody
Dose:1000mg IV infusions 2 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
Tocilizumab
Humanized
Binds to soluble & membrane bound
IL-6
Dose:4mg/kg IV increase up 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
TNF-alpha blocking agents
Adalimumab
IgG1 anti TNF alpha
Dose:40 mg s/c Every other week
Indications Mod-severe RA ,JIA,
Psoriasis, Ulcerative
colitis, Chrons disease
PK t half: 10-20 days
Certolizumab
Humanized Anibody Fab fragment
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
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
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
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
Adverse effects of TNF-alpha
inhibitors
•Risk of infections
• Increase chance of skin cancers
•Alopecia
• Hypertrichosis
•Erosive lichen planus
•Cutaneous pseudo lymphoma
IL-I inhibitors
Drug MOA Dose 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
USTEKINUMAB SECUKINUMAB
MOA:IL-12 &23
antagonist
S/c route
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
Belimumab
B lymphocyte stimulation( BLyS)
IV infusion 10mg/kg W0,W2,W6
Sero positive SLE
A/E:Risk of infection, Depression
Tofacitinib
Target specific DMARDS
JAK3/JAK 1
Differentiation& proliferation inhibited
Indications: Allograft rejection, mod to severe RA,
PsA, Psoriasis, JIA
A/E:Risk of infections, neutropenia/anemia
Management
Guidelines……
EULAR guidelines
First line Methotrexate
(short term glucocorticoides)
Conventional DMARDs combinations
bDMARDs
SUMMARY
THANK YOU……

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Rheumatoid arthritis : Biological DMARDs