Treatment of rheumatoid arthritis11.ppt - CiplaMed · 2014. 5. 30. · Rheumatoid Arthritis Disease Activity Index 0-10 < 2.2 >2.2 & 4.9 Patient Activity Scale

Treatment of

Rheumatoid Arthritis

Provided as a service by CiplaMed

Rheumatoid Arthritis

(RA)

Principles of Management

Controlling RA

Goals of management -

• Decrease joint inflammation & pain


• Decrease joint inflammation & pain

• Increase joint function

• Prevent joint destruction

• Better quality of life

Clinical Factors necessary

for Therapeutic


Decision-Making

Arthritis & Rheumatism 2008;59(6):762–784

RA Disease Duration

• < 6 months - early disease

• 6–24 months - intermediate disease duration

• > 24 months - long or longer disease duration


For biologic therapies, early disease was further

subdivided by disease duration of < 3 months or 3–6

months, when disease activity was high.

Instruments used to Measure

RA Disease Activity

Instrument Score range Low Moderate High

Disease Activity Score in 28 joints

0–9.4 < 3.2 > 3.2 & < 5.1 > 5.1

Simplified Disease Activity Index

0.1–86.0 < 11 > 11 & < 26 > 26


Activity Index

Clinical Disease Activity Index

0-76.0 < 10 >10 & < 22 > 22

Rheumatoid Arthritis Disease Activity Index

0-10 < 2.2 > 2.2 & < 4.9 > 4.9

Patient Activity Scale I or Patient Activity Scale II

0-10 < 1.9 > 1.9 & < 5.3 > 5.3

Routine Assessment Patient Index Data

0-30 < 6 > 6 & < 12 >12

Prognostic Factors for RA

RA patients with features of a poor prognosis have -

• Functional limitation (defined using measurement scales like Health

Assessment Questionnaire score or variations of this scale),

• Extraarticular disease (e.g., presence of rheumatoid nodules,


• Extraarticular disease (e.g., presence of rheumatoid nodules,

secondary Sjogren’s syndrome, RA vasculitis, Felty’s syndrome, and

RA lung disease),

• Rheumatoid factor positivity, positive anti-cyclic citrullinated peptide

antibodies, or

• Bony erosions by radiography

Treatment


Therapeutic Approach

• NSAIDs (Non Steroidal Anti-Inflammatory Drugs)

• DMARDs (Disease Modifying Anti-Rheumatic Drugs)

• Corticosteroids


• Corticosteroids

• Biologics


NSAIDs

• Most commonly prescribed drugs for RA

• Only for symptom relief

• Careful monitoring for adverse events necessary for long term use

• Use should be minimized when disease control is achieved with


• Use should be minimized when disease control is achieved with

DMARDs

• Prostaglandins are important mediators of both pain and

inflammation. NSAIDs Inhibit prostaglandin synthesis by blocking

COX-1 and COX-2

• E.g. – diclofenac, piroxicam, celecoxib

Indian Journal of Rheumatology 2008;3(3)

DMARDs

• Indicated in all patients fulfilling ACR criteria for RA

• Initiation of DMARDs - not to be delayed beyond 3 months in

whom, in spite of adequate treatment with NSAIDs, there is

ongoing joint pain, significant morning stiffness or fatigue, active


ongoing joint pain, significant morning stiffness or fatigue, active

synovitis, or persistent elevation of ESR or CRP

• Treatment is lifelong; if remission is achieved and maintained for

a year, drugs may be decreased or dose may be reduced

• E.g. - Methotrexate, Leflunomide, Sulphasalazine,

HydroxychloroquineIndian Journal of Rheumatology 2008;3(3)

Methotrexate – Mode of Action

Folic acid

dihydrofolate reductase

Dihydrofolate

Methotrexate


dihydrofolate reductase

Dihydrofolate

Tetrahydrofolate Cofactors

Purines Pyrimidines

Methotrexate

Leflunomide – Mode of Action

Dihydroorotate dehydrogenase

Glutamine, bicarbonate, aspartate

Dihydroorate

Orotate A77 1726


dehydrogenaseOrotate

Uridine monophosphate

Pyrimidine mononucleotides

RNA DNA

T cell proliferation

Hydroxychloroquine, Sulphasalazine

• Hydroxychloroquine - changes antigen

presentation or effects on the innate immune

system


system

• Sulphasalazine - It is not entirely clear how

sulphasalazine work in RA

Provided as a service by CiplaMed Arthritis & Rheumatism 2008;59(6):762–784

A - Disease duration < 6 months

Disease Activity

Features of poor prognosis


Moderate or HighLow

Start here

Provided as a service by CiplaMedHCQ-hydroxychloroquine; LEF -leflunomide; MTX-methotrexate;

SSZ-sulfasalazine; MIN-minocycline

With Without With Without

LEFMTXSSZ

HCQMIN

LEFMTX

MTX+HCQ

SSZMTX+SSZ

MTX+SSZ+HCQ

B - Disease duration 6 - 24 months

Disease Activity



Moderate or HighLow

Start here


prognosis prognosis


LEFMTXSSZ

HCQ

LEFMTXSSZ

SSZ+HCQ

MTX+HCQ+SSZ

MTX+LEFMTX+SSZMTX+HCQ

MTX+HCQ+SSZ

C - Disease duration > 24 months

Disease Activity



HighLow or Moderate

Start here


prognosis prognosis


LEFMTXSSZ

MTX+HCQ

LEFMTX SSZMTX+LEF

MTX+HCQ+SSZ

MTX+LEFMTX+SSZMTX+HCQ

MTX+HCQ+SSZ

Corticosteroids

• Potent anti-inflammatory effects, hence effective for

symptomatic relief

• Low dose oral prednisolone (5-10mg/day) – for short

duration, beneficial in RA of < 2 years


duration, beneficial in RA of < 2 years

• Intraarticulaar corticosteroids –

– indicated if a single joint or only a few joints are inflamed

– injection in the same joint should not be repeated before 3

months

– No more than 3 injections per joint is advisable in a year

Indian Journal of Rheumatology 2008;3(3)

Biologics

• Indicated in patients fulfilling ACR criteria for RA

• Fast onset of action

• Can be combined with DMARDs such as


• Can be combined with DMARDs such as

methotrexate

• Provide higher rates of remission

• Well tolerated

Biologics – Mode of ActionCytokine

Receptor

Inflammatory

signal

Receptor

No signal

Antibody

Normal interaction Neutralization of cytokines


Antibody Receptor

antagonist

No signal No signal

Anti-inflammatory

cytokine

Suppression of

inflammatory cytokines

Receptor blockade Activation of anti-inflammatory pathways

Biologics

ACR Recommendations


for Use of Biologics in RA

Arthritis & Rheumatism 2008;59(6):762–784

Patients with RA < 6 months

Disease Activity

Features of poor

prognosis

Start here

Without

High for <3 monthsLow or moderate

< 6 months


See fig. A Non-Biologic DMARDs

Anti-TNF & MTX

Cost or insurance coverage limitations

prognosis

See fig. A Non-Biologic DMARDs

With

With

Without

High for 3-6 months

Patients with RA > 6 months who

failed prior MTX monotherapy

Disease Activity

Start here

HighLow


See fig. B & C Non-Biologic DMARDs

Features of poor

prognosis

Anti-TNF

With

Moderate

Without

Patients with RA disease duration of > 6

months, failed prior MTX combination

therapy or after sequential administration of

other DMARDs

Start here


See fig. B & C Non-Biologic DMARDs

Disease Activity

Features of poor

prognosis

Abatacept Or

Anti-TNF Or

Rituximab

Moderate or HighLow

WithWithoutSee fig. B & C Non-Biologic DMARDs

OrAnti TNF

Baseline Evaluations

Therapeuticagents

CBC Liver transaminases

Creatinine HepatitisB & C testing

Ophthal-mologic

examination

HCQ


LEF

MTX

MIN

SSZ

Biologics

X – recommended tests

Self Care

• Take the prescribed medicine as advised by the doctor

• Do not miss any dose of the medicine

• Tell the doctor in case of any continued side effects


• Tell the doctor in case of any continued side effects

• Stop smoking

• Decrease / avoid alcohol intake

• Exercise regularly

Treatment of rheumatoid arthritis11.ppt - CiplaMed · 2014. 5. 30. · Rheumatoid Arthritis Disease Activity Index 0-10 < 2.2 >2.2 & 4.9 Patient Activity Scale

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