Rheumatoid Arthritis

Hendra Wana Nuramin

Department of Pharmacology
Medical Faculty
Lambung Mangkurat University

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Skenario 1
Ny. SB seorang ibu berusia 55 tahun, dibawa ke
poli Geriatri RS dengan keluhan nyeri sendi-sendi
kaki dan lutut, yang sudah dialami selama satu
tahun terakhir. Tampak bengkak dan panas di
sekitar sendi, terutama pada sendi-sendi kecil dan
sendi kaki. Sendi terasa kaku terutama di pagi hari.
Gejala ini sudah lama dirasakan oleh ibu tersebut
namun sering kambuh terutama bila kondisi
lingkungan yang dingin, keadaan Ny. SB sampai
saat ini tidak dapat melakukan aktivitas. Hasil lab
menunjukkan RA (+). Ners Zahra mencoba untuk
memberikan asuhan keperawatan pada Ny. SB.
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Rheumatoid Arthritis
A chronic autoimmune disease characterized
by the inflammation of the synovial joints
Has a symmetrical bilateral effect on joints
Results in joint deformity and immobilization
Multiple factors increase ones risk
Progressive, systemic, inflammatory disorder
Unknown etiology (multifactor?)
Characterized by
Symmetric synovitis
Joint erosions
Multisystem extra-articular manifestations
can result in severe disability
(The Arthritis Society, 2012; Gulanick & Myers, 2011; Firth, 2011)
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The Importance of Early
Diagnosis
RA is progressive, not benign
Structural damage/disability occurs within
first 2 to 3 years of disease
Slower progression of disease linked to
early treatment
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Epidemiology
Incidence
1.4/10000 male, 3.6/10000
females
Prevalence 0.5-2 %
male:female 1:3
Worldwide distribution
higher in native Americans
absent in some parts of
Africa
Onset any age but
maximum
40 - 70 years in women
60 - 70 years in men

Unclear
Autoimmunity Normal
antibodies become
autoantibodies and
attack the tissue.
Infectious agents
Genetic Factor
Gender
Endocrine (CRH,
estrogen synthase)
Stressful events
Smoking
Etiology
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Clinical features
Symmetrical deforming polyarthritis
affects synovial lining of joints, bursae and tendons
more then just joint disease
Presentation
Variable
Gradual or acute/subacute
Palindromic
Monoarticular
Symmetrical, diffuse small joint involvement
Functional impairment: related to underlying
disease activity and joint damage due to previous
activity
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Diagnosis
Investigations
Haematology
Hb, wcc, plts, ESR
Biochemistry
LFT, CRP
Immunology
RhF, ANA
Microbiology
viral titres
Radiology
XR, bone scan, MRI

Differential diagnosis
Post viral (parvo,
rubella)
Reactive arthritis
SLE
Polyarticular Gout
Polyarticular OA
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ACR 1987 Criteria for Diagnosis
Four or more of the following criteria must be
present:
Morning stiffness > 1 hour
Arthritis of > 3 joint areas
Arthritis of hand joints (MCPs, PIPs, wrists)
Symmetric swelling (arthritis)
Serum rheumatoid factor
Rheumatoid nodules
Radiographic changes
First four criteria must be present for 6 weeks
or more
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2010 ACR/EULAR
Classification Criteria for RA
JOINT DISTRIBUTION (0-5)
1 large joint 0
2-10 large joints 1
1-3 small joints (large joints not counted) 2
4-10 small joints (large joints not counted) 3
>10 joints (at least one small joint) 5
SEROLOGY (0-3)
Negative RF AND negative ACPA 0
Low positive RF OR low positive ACPA 2
High positive RF OR high positive ACPA 3
SYMPTOM DURATION (0-1)
<6 weeks 0
6 weeks 1
ACUTE PHASE REACTANTS (0-1)
Normal CRP AND normal ESR 0
Abnormal CRP OR abnormal ESR 1
6 = definite RA
Rheumatoid Arthritis:Treatment
Principles
Confirm the diagnosis
When damage begins early, start
aggressive treatment early
Use the safest treatment plan that
matches the aggressiveness of the
disease
Monitor treatment for adverse effects
Monitor disease activity, revise Rx as
needed

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Goals of Therapy
Control disease activity
To relieve pain, stiffness, swelling, fatigue
To prevent joint damage/disability
To improve quality of life
Slow progression/rate of joint damage
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Management
Education
Physical therapies: Rest, Exercise,
Diet/weight control,
physical/occupational therapy
Drugs
analgesics
NSAIDs
DMARDs
Immunotherapies
Steroids ia, po, im, iv
Surgery
(Arthritis Foundation, 2012)
Walking
Light jogging
Water aerobics
Cycling
Yoga
Tai chi
stretching
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Pharmacotherapy
Pharmacological treatment of RA can be divided
into :
Disease-modifying antirheumatic drugs (DMARDs)
Anti-inflammatory agents
Glucocorticoids
Non-steroidal anti-inflammatory drugs (NSAIDs,
most also act as analgesics)
Analgesics
Acetaminophen
Opiates
Lidocaine topical

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Steroids work
here
Steroids work
here
NSAIDs work
here
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COX-1
COX-2
COX-3
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OPIOID
Receptor : analgetic,
respiratory depression,
miosis, euphoria,
deacrease bowel motility
1 : in CNS
2 : in PNS
Receptor : analgetic,
respiratory depression,
miosis, sedative <
receptor
Receptor : respiratory
depression
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COX-1 membentuk prostaglandin (proses normal
tubuh) proteksi mukosa lambung
COX-2 berperan dalam peradangan
COX-3 varian dari COX-1, yang terdistribusi di
sistem saraf pusat.
Tidak mempengaruhi lambung paracetamol
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Efek samping AINS terhadap asma
Penghambatan COX mengarahkan
metabolisme asam arakidonat ke arah
jalur lipoksigenase leukotrien
bronkokonstriksi
COX 2 Selektif celecoxib, rofecoxib,
valdecoxib.
Penghambatan secara selektif terhadap
COX-2 mengkatalisis pembentukan
tromboksan A2 (pembekuan darah dan
bersifat vasokonstriktor blood clots
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Non-steroidal anti-inflammatory drugs (NSAIDs)

Examples General Use Side Effects Nursing
Considerations
Aspirin, ibuprofen,
naproxen, COX-2
inhibitors, propionic
acid, phenylacetic
acid
anti-
inflammatory:
Used in the
management
inflammatory
conditions
Antipyretic:
used to control
fever
Analgesic:
Control mild to
moderate pain

Nausea
Vomiting
Diarrhea
Constipation
Dizziness
Drowsiness
Edema
Kidney failure
Liver failure
Prolonged
bleeding
Ulcers

Use cautiously
in patients with
hx of bleeding
disorders
Encourage pt
to avoid
concurrent use
of alcohol
NSAIDs may
decrease
response to
diuretics or
antihypertensive
therapy

(The Arthritis Society, 2011; Day et al., 2010)
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Corticosteroids
Examples General Use Side Effects Nursing
Considerations
Cortisone,
hydrocortisone,
prednisone,
betamethasone,
dexamethasone
Used in the
management
inflammatory
conditions
When NSAIDS
may be
contraindicat
ed
Promptly
improve
symptoms of
RA
Increased
appetite
Weight gain
Water/salt
retention
Increased
blood pressure
Thinning of skin
Depression
Mood swings
Muscle
weakness
Osteoporosis
Delayed
wound healing
Onset/worseni
ng of diabetes
Take medications
as directed
(adrenal
suppression)
Used with caution
in diabetic
patients
Encourage diet
high in protein,
calcium,
potassium and low
in sodium and
carbohydrates
Discuss body
image
Discuss risk for
infection

(The Arthritis Society, 2011; Day et al., 2010)
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Disease-modifying anti-rheumatic drugs(DMARDS)
Examples General Use Side Effects Nursing
Considerations
Methotrexate
(the gold
standard),
gold salts,
cyclosporine,
sulfasalazine,
azathioprine

immunosuppr
essive activity
Reduce
inflammation
of rheumatoid
arthritis
Slows down
joint
destruction
Preserves joint
function

Dizziness,
drowsiness,
headache
Pulmonary fibrosis
Pneumonitis
Anorexia
Nausea
Hepatotoxicity
Stomatitis
Infertility
Alopecia
Skin ulceration
Aplastic anemia
Thrombocytopenia
Leukopenia
Nephropathy
fever
photosensitivity
May take
several weeks to
months before
they become
effective
Discuss
teratogenicity,
should be taken
off drug several
months prior to
conception
Discuss body
image


(The Arthritis Society, 2011; Day et al., 2010)
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Biologic Response Modifiers (Bioligics)
Examples General Use Side Effects Nursing
Considerations
Etanercept,
anakinra,
abatacipt,
adalimumab,
Infliximab
(Remicade)

Used in the
management
inflammatory
conditions
When NSAIDS
may be
contraindicat
ed
Promptly
improve
symptoms of
RA
Increased appetite
Weight gain
Water/salt
retention
Increased blood
pressure
Thinning of skin
Depression
Mood swings
Muscle weakness
Osteoporosis
Delayed wound
healing
Onset/worsening of
diabetes



Take
medications as
directed
(adrenal
suppression)
Encourage diet
high in protein,
calcium,
potassium and
low in sodium
and
carbohydrates
Discuss body
image
Discuss risk for
infection

(The Arthritis Society, 2011; Day et al., 2010)
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Pain unpleasant
sensory and
emotional
experience.
Analgetic any
member of the
group of drugs used
to
achieve analgesia
relief from pain
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DMARDs
Reduce swelling & inflammation
Improve pain
Improve function
Have been shown to reduce radiographic
progression (erosions)

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DMARDs
Traditional small molecular
mass drugs (synthesised
chemically):
Azathioprin
Ciclosporin (cyclosporine
A)
D-penicillamine
Gold salt
Hydroxychloroquine
Leflunomide
Methotrexate (MTX)
Minocycline
Sulfasalazine (SSZ)
Biological agents
Tumor necrosis factor (TNF)
blockers: etanercept
(Enbrel), infiximab
(Remicade), adalimumab
(Humira), Certolizumab
pegol (Cimzia)sc (CDP-870)
Anti-B cell (CD20) antibody :
rituximab (Rituxan,
MabThera), Ocrelizumab
Interleukin-1 blockers :
anakinra (Kineret)
Blockers of T cell activation
(costimulation blockers):
abatacept (Orencia)
Anti-Blys antibody:
Belimumab
Anti-IL-6 receptor MAb:
Tocilizumab (ActemraTM)
Protein tyrosine kinase
inhibitor : Imatinib (Gleevec)
CPH82 (influences the cell
cycle & cell proliferation):
Reumacon
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Disease-Modifying antirheumatic Drugs (DMARDs)
Drug Mechanisms Common Usual
of action adverse effects Dosing regimens
Injectable gold Inhibits: macorphg, Mucocutan.eruptions 50 mg/wk i.m to total
Aurothioglucose angiogenesis,prot. Proteinuria dose of 1000 mg then
Gold sodium kinase C Thrombocytopenia 50 mg i.m q 2-4 wk
thiomalate
Oral gold Inhibits: macrophg, Diarrhea, Mucocutan. 3 mg p.o.b.i.d
Auranofin PMN function eruptions
Antimalarials
Hydroxychlorqn Inhibits: cytokine Diarrhea, mucocutan. 400 mg p.o.,q.d
Chlorqn phosphat secretion,lysoso- eruptions 250 mg p.o.,q.d
mal enzymes, ma
crophg.function
D-Penicillamine Inhibits: helper T Mucocutan.eruptions 500-1000 mg p.o.,q.d
cell function, angio Proteinuria
genesis Thrombocytopenia

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Disease-Modifying antirheumatic Drugs (DMARDs)
Drug Mechanisms Common Usual
of action adverse effects Dosing regimens
Sulfasalazine Inhibits: B cell Nausea, abd.pain, 1000 mg p.o.,b.i.d
responses, angio- diarrhea, rash or t.i.d
genesis
Methotrexate Dihydrofolate Mucocutan.eruptions 7.5-25 mg/wk p.o.
reductase inhibitor, Bone marrow (may also be admi-
Antiinflammatory via Nausea, diarrhea, nistered parente-
induction of adeno- Hepatic abnormalities rally SC or IM)
sine release,inhibits
chemotaxis
Leflunomide Inhibits pyrimidine Hepatic abnorm. 20 mg/day p.o.
synthesis Diarrhea,nausea (initial loading dose
of 100 mg/day for
3 days


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Disease-Modifying antirheumatic Drugs (DMARDs)
Drug Mechanisms Common Usual
of action adverse effects Dosing regimens
Anakinra IL-1 receptor Injection site 100 mg s.c.
antagonist reactions, injection daily
Infections
Adalimumab TNF antibody Injection site 40 mg s.c. inj.
(human) reaction, q. 14 days
Opportunistic
infections
Infiximab TNF antibody Infusion reactions 3 mg/kg i.v. slow
(chimeric) Opportunistic infusion wk 0,2,6,
infection then every 8 wk
Etanercept Soluble TNF Injection site 25 mg s.c. inj.
receptor reactions twice weekly or
Opportunistic 50 mg/wk s.c.
infections
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Disease-Modifying antirheumatic Drugs (DMARDs)
Drug Mechanisms Common Usual
of action adverse effects Dosing regimens
Cyclosporine Inhibits: synthesis Hypertension 2.5-4 mg/kg p.o.
of IL-2 & other T Renal insuff. q.d.
cell cytokines Hirsutism
Azathioprine Inhibits DNA Bone marrow 1-2 mg/kg p.o,q.d
synthesis supprression
Mycophenolate Inhibits lymphocyte GI, leukopenia 1.0-1.5 g p.o,b.i.d
Mofetil proliferation nausea,hepatic
abnormalities
Cyclophos- Crosslinks DNA Nausea, emesis 1-2 mg/kg p.o,q.d
phamide & inhibits cellular Bone marrow
proliferation suppression
Ovarian failure
Hemorrhagic cystitis
risk of cancer
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Disease-Modifying antirheumatic Drugs (DMARDs)
Drug Mechanisms Common Usual
of action adverse effects Dosing regimens
Minocycline Inhibits biosyn- Diarrhea,nausea 100 mg p.o, b.i.d
thesis & activity Photosensitivity
of MMPs
Rituximab Anti-CD20 mono- Hypotension 1 g IV q.14 days
clonal antibody Hypertension
(chimeric) RA exacerb.

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Methotrexate (MTX)
Dihydrofolate reductase inhibitor
thymidine & purine nucleotide synthesis
Gold standard for DMARD therapy
7.5 30 mg weekly
Absorption variable
Elimination mainly renal
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MTX adverse effects
Hepatotoxicity
Bone marrow suppression
Dyspepsia, oral ulcers
Pneumonitis
Teratogenicity
Folic acid reduces GI & BM effects
Monitoring
FBC, ALT, Creatinine
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Pathogenesis of RA
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Tumour Necrosis Factor (TNF)
TNF is a potent inflammatory cytokine,
produced mainly by macrophages and
monocytes. Major contributor to the
inflammatory and destructive changes
that occur in RA.
Blockade of TNF results in a reduction in a
number of other pro-inflammatory
cytokines (IL-1, IL-6, & IL-8)
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TNF- Inhibitor Drugs
Certolizumab pegol
Infliximab (Remicade )
Adalimumab
Golimumab
Etanercept
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Adverse Effects of TNF-
Inhibitors
Injection site reactions
Increased risk of bacterial, viral, and/or
fungal infections
Bone marrow suppression
Generation of antibodies to drugs,
resulting in reduced efficacy over time
Drug-induced lupus-like syndromes
Emergence of lymphoma and skin
cancers over long-term use
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Combination therapy is well tolerated and
associated with no significant increase in the
rate of adverse events compared with
monotherapy.

Methotrexate-sulfasalazine,
Methotrexate-chloroquine,
Methotrexate-ciclosporin,
Methotrexate-leflunomide,
Methotrexate-intramuscular-gold
Methotrexate-doxycycline
are effective combination regimens.


Nat Clin Pract Rheumatol. 2007; 3(8):450-458.

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Triple DMARD therapy is better than
various DMARD monotherapy and dual
therapy regimens.
Methotrexate and hydroxychloroquine
may have synergistic anti-inflammatory
properties.
Clinical trial evidence to support the use of
other methotrexate and sulfasalazine
combinations is often weak or lacking.
Nat Clin Pract Rheumatol. 2007; 3(8):450-458.

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STEM CELL THERAPY
Hematopoietic stem cells may be beneficial as a
treatment for rheumatoid arthritis
Bingham SJ, Moore JJ. Stem cell transplantation for
autoimmune disorders. Rheumatoid arthritis. Best
Pract Res Clin Haematol 2004; 17(2): 263-76.

Hematopoietic stem cell transplantation is being
investigated as a treatment for patients with
severe refractory rheumatoid arthritis that is
unresponsive to conventional therapies. The stem
cells are well tolerated in patients with rheumatoid
arthritis. The authors review the research and
suggest future protocols for treatments.

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Prognosis
Life expectancy reduced by
7 years in men
3 years in women
Severe morbidity
sudden onset do better than gradual
early knee involvement bad
Bad RA has a worse prognosis than IHD or
Hodgkins
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Risk Factors for Increased
Morbidity and Mortality in RA
Social factors
Low socioeconomic status
Lack of formal education
Psychosocial stress
Low HAQ scores
Physical factors
Extra-articular manifestations
Elevated CRP and ESR
High titers of RF
Erosions on x-ray
Duration of disease
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Rheumatoid Arthritis:
Treatment Plan Summary
A variety of treatment options are
available
Treatment plan should match
The current disease activity
The documented and anticipated pace of
joint destruction
Consider a rheumatology consult to help
design a treatment plan

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Contact: hendranuramin@gmail.com