This document discusses biological therapies for rheumatic diseases. It provides a historical overview of biological therapies and reviews various cytokine inhibitors including tumor necrosis factor (TNF) inhibitors, interleukin inhibitors, T-cell and B-cell directed therapies. It summarizes several TNF inhibitors including infliximab, adalimumab, etanercept, golimumab, and certolizumab pegol. The document also reviews strategies for using biologics in rheumatoid arthritis and considerations for special patient populations.
7. BIOLOGIC VERSUS SYNTHETIC DMARDS
1. Biologics can be effective where conventional DMARDs have failed.
2. Biologics, and specifically the anti-TNF biologics, can have a very rapid onset of action: same day.
3. Radiographic efficacy of the anti-TNF agents exceeded expectations.
4. Anti-TNF agents, and biologics in general, are surprisingly well tolerated and relatively safe.
5. Biologics have a well-defined and specific mechanism of action
10. TUMOR NECROSIS FACTOR INHIBITORS
The pathophysiology of rheumatoid arthritis depicted as a cascade, in which TNF is upstream from IL-1, IL-6, and IL-8
11.
12. INFLIXIMAB
• 5 mg/kg with or without MTX, at 0, 2, and 6 weeks, then every 8 weeks
• Rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, Crohn disease, and
ulcerative colitis
• S.E: severe infusion reactions
anti-infliximab monoclonal antibodies
13. ADALIMUMAB (HUMIRA)
• Subcutaneous 40 mg every other week
• RA, JIA, PsA, AS, nr-axSpA, Crohn’s disease, psoriasis.
• MTX
• No adjustment of dosing for body weight or size, nor for age or metabolic status
(except advanced renal failure)
14. ETANERCEPT (ENBREL)
• MTX
• 50 mg SC weekly or 25 mg twice weekly
• JIA,RA, PsA, and AS.
• Not effective for ulcerative colitis
15. GOLIMUMAB (SIMPONI)
• RA
• long dosing interval
• 50 mg subcutaneously once a month
• Intravenous golimumab (Simponi Aria)
16. CERTOLIZUMAB PEGOL (CIMZIA)
• linked to polyethyleneglycol (PEG) for greater stability & a longer half-life
• RA
• Various DMARDs
• Higher risks for infection
• Single bi-weekly subcutaneous 200 mg injection or as 2injections given /4weeks
17. EFFICACY OF TUMOR NECROSIS FACTOR
INHIBITORS
• Rheumatoid Arthritis
• Psoriatic Arthritis (PsA)
• Ankylosing Spondylitis
• Other Considerations:
Treatment in Other Autoimmune Conditions:Crohn’s,JIA, psoriasis, idiopathic and
spondyloarthropathy-related anterior uveitis, sarcoidosis, Sjِ gren’s syndrome, Behçet’s
disease, inflammatory myopathies, and various types of vasculitis, SLE
20. VACCINATIONS
• It is preferred to have all recommended vaccinations before initiating treatment
• Live vaccines with TNF inhibitors is not recommended
21. TOXICITY
Infusion and Injection
Site Reactions
Antigenicity Infection Malignancy
Autoimmune
Disorders.
Demyelinating
Syndromes
Congestive Heart
Failure
22. INTERLEUKIN-6 INHIBITORS
TOCILIZUMAB (ACTEMRA)
• SE: Infections, tuberculosis
Cancer
Elevated transaminases
Cytopenias: leukopenia, neutropenia, thrombocytopenia
Elevations of cholesterol
‘Masking’ of the acute phase response
• Dosing: 4 or 8 mg/kg given at 4-week intervals
subcutaneous 162 mg given once weekly
Other interleukin-6 antagonists: sarilumab, sirukumab, Olokizumab, clazakizumab
23. INTERLEUKIN-1 INHIBITORS
• Kineret ,Canakinumab, Rilonacept
• Approved for the treatment of RA, but results in practice were disappointing (slower, daily
subcutaneous injections, cutaneous reactions, less effective)
• Cryopyrin-associated inflammatory syndromes
• Improved efficacy
• High incidence of severe infections
26. T-CELL DIRECTED THERAPY
Abatacept (Orencia)
• Monotherapy or combined with MTX
• IV 500, 750, or 1000 mg based on body weight, given every 4 weeks.
• SC at 125 mg weekly
High rate of severe infections
28. B-CELL DIRECTED THERAPY
• Professor Jonathan Edwards proposed that IgG-
rheumatoid factors play a central role in the
pathophysiology of rheumatoid arthritis
• Hypothesized that B-cell depletion would be
effective
29. RITUXIMAB
• Non-hodgkin lymphoma
• off-label of many autoimmune diseases
• (ANCA)-associated vasculitis, SLE, multiple sclerosis
• SE:infusion reactions
progressive multifocal leukoencephalopathy
• 500 or 1000 mg given intravenously twice with two weeks in between
• 6-monthly repeat courses
• Monotherapy or combination with DMARDs
39. • Patient who had failed numerous DMARDs and had highly active disease
• Pattient who had failed methotrexate (MTX) and at least one other DMARDs
Which Patients The Biologics Should Be Used?
53. abatacept achieved similar ACR responses as infliximab
the responses and the adverse events were similar
tocilizumab was shown to be superior to adalimumab
59. BIOLOGICS IN PEDIATRIC PATIENTS
Commonly Used Medications in Juvenile Idiopathic Arthritis
60. A relatively high prevalence of lymphoma in children and adolescents treated with anti-TNF agents
JIA itself is associated with an elevated risk for malignancies
61. BIOLOGICS IN ELDERLY PATIENTS
comorbidities treatments osteopenia joint damage sarcopenia complications
The elderly respond equally well, and donot have
more side effects, to treatment with adalimumab,
etanercept, infliximab, rituximab, or tocilizumab