Download Rheumatoid Arthritis

Rheumatoid Arthritis:
Treatment options in 2017
Chacko J. Alappatt, M.D., F.A.C.P., F.A.C.R
Rheumatoid Arthritis (RA) Fast facts
• PREVALENCE : An estimated 1.5 million
adults in the United States have rheumatoid
arthritis. Affects 0.5-1.0% of population
• Women are two to three times as likely to be
affected as men.
• Rheumatoid arthritis (RA) is an inflammatory
systemic disease, with the hallmark of
symmetric peripheral polyarthritis.
What is Rheumatoid Arthritis (RA)?
• A chronic systemic autoimmune
inflammatory disease that causes aggressive
inflammatory changes in the synovium which
causes joint pain/stiffness/swelling and
ultimately leads to joint damage and
functional debility
Rheumatoid Arthritis (RA)
Rheumatoid Arthritis- Joint Distribution
Rheumatoid Factor
– AUTOANTIBODIES
(OFTEN IgM) WITH
SPECIFICITY FOR THE
Fc PORTION OF THE
IgG MOLECULE
– MAJOR LABORATORY
HALLMARK OF RA
– ASSOCIATED WITH
MORE SEVERE
DISEASE,
EXTRAARTICULAR
MANIFESTATIONS
– NOT SPECIFIC FOR RA
Cyclic Citrullinated Peptide (CCP) Ab
• Sensitivity/Specificity
for RA: 80%/96-98%
• Can be detected up to
10 years prior to onset
of symptoms
• Marker for more
aggressive disease
• Readily available (yet
not part of ‘arthritis
panels’??)
Rheumatoid Arthritis –ACR Criteria (1987)
•  4 OF THE FOLLOWING CRITERIA MUST BE
PRESENT IN ORDER TO CLASSIFY AS RA:
–
–
–
–
–
–
–
AM STIFFNESS > 1 HR
ARTHRITIS IN > 3 JOINTS
ARTHRITIS IN PIPS, MCP, WRISTS
SYMMETRIC ARTHRITIS
POSITIVE RHEUMATOID FACTOR
RHEUMATOID NODULES
RADIOGRAPHIC CHANGES:
• PERIARTICULAR OSTEOPENIA
• EROSIONS
(≥6 weeks)
(≥6 weeks)
(≥6 weeks)
(≥6 weeks)
RA 2010 Diagnostic Criteria
Etiology of Rheumatoid Arthritis (RA)
Hereditary predisposition/environmental trigger
Autoimmunity
Release inflammatory mediators/cytokines
Chronic inflammation of the synovial tissue lining joint capsule
Proliferation of the synovium into Pannus
Pannus invades cartilage and bone surface producing bone erosion
Joint Destruction
Rheumatoid Arthritis Treatment Goals
•
•
•
•
RELIEVE PAIN, SWELLING, FATIGUE
IMPROVE JOINT FUNCTION
STOP JOINT DAMAGE
PREVENT DISABILITY AND DISEASERELATED MORBIDITY
• MINIMIZE/AVOID ADVERSE EVENTS
– (MONITOR FOR TOXICITY)
RA Management in 2017
Goal
• Zero Disease Activity
• Remission
Processes
Early Treatment
Aggressive Treatment
Monitor Disease Activity
Tools
Traditional DMARDs
Biologic DMARDs
Combination Therapy
Non Biologic small molecule DMARDs
•
•
•
•
•
Hydroxychloroquine
Sulfasalazine
Leflunomide
Methotrexate
(Prednisone/Corticosteroid)
Biologic Response Modifier Drugs
Important information: Biologics
• Typically given by SC injection or infusion
• Complex molecules made in living cells
• All modify the immune system; can
predispose to infection
• ? Associated with Malignancy
• Before initiation, screen for latent
infections: Tuburculosis, Hepatitis, HIV
• live vaccines (Zoster) contraindicated;
vaccinate prior to initiation
Important information: Biologics
• Most common adverse events: injection site
reactions, “nasopharyngitis”, headache
• Abatacept (Orencia) : caution in COPD
• Combining two biologics: Not recommended
• Tofacitinib citrate (Xeljanz): watch Lipids
• Rituximab (Rituxan): PML and use in
malignancy
• Other: CHF, Bowel perforations,
Demyelination, “Lupus like Syndrome”
Tumor Necrosis Factor Antagonists
Infliximab (Remicade)
Etanercept (Enbrel)
Certolizumab (Cimzia)
Golimumab (Simponi)
Adalimumab (Humira)
B-Cell Depletion: Rituximab
Co-stimulation Inhibitor: Abatacept
Tocilizumab (Actemra): IL-6 (-)
Jak inhibition: Tofacitinib (Xeljanz)
Biosimilars: the new Horizon
Properties
Generics
Biosimilars
Size
Small
Large
Molecular Weight
<500-900 Daltons
4000- >140,000 Daltons
Structure
Simple / well defined
Complex
Manufacturing
Predictable Chemical
process: identical copy
Specialized process to
make similar copy
Complexity
Easy to fully
characterize
Difficult to
characterize
Stability
Relatively stable
Sensitive to storage
Adverse immune react
Lower potential
Higher potential
Manufact. Quality
<50
> 250
Approval requirements Small Clinical Trials
Large Clinical Trials
The new Horizon: Biosimilars
• 4/2016: FDA approves Inflectra (Pfizer),
biosimilar for Infliximab (Remicade-Jansen)
• 8/2016: FDA approves Erelzi (Sandoz),
biosimilar for Etanercept (Enbrel-Amgen)
• 9/2016: FDA approves Amjevita (Amgen),
biosimilar for Adalimumab (Humira-Abbvie)
Your patient John, a 51 year old male, who takes
Enbrel for his RA is interested in the Zoster
vaccination. You advise
A.
B.
C.
D.
Good idea, arrange for
vaccination
He is not a candidate for
vaccination
Can get vaccination but has to
be off Enbrel for a month
before and after vaccination
Good idea but he will need to
wait until age 60
10
Your patient Alexandra, a 58 year old female with Rheumatoid
Arthritis who takes Methotrexate (MTX) and Enbrel develops a
culture positive (E. Coli) urinary tract infection. You advise
A.
B.
C.
Treat with Bactrim; continue MTX;
hold Enbrel
Treat with Cipro; hold Enbrel
Treat with Cipro; continue MTX and
Enbrel
10
Which of the following Rheumatoid Arthritis
medications can increase serum cholesterol?
A.
B.
C.
D.
Etanercept (Enbrel)
Tofacitinib (Xeljanz)
Tolcilizumab (Actemra)
Rituximab (Rituxan)
10