Principles of Management of

Goals of Management

Relief of Pain

Suppression of active & progressive disease

Conservation & restoration of function in affected joints

Major SectionsTherapeutic classification

Tools of management

Initiation

Monitoring

Readjustment of treatment

Full remission and weaning

Concluding remarks

1.

Therapeuti

c

Classificati

on of RA

Markers of Poor Prognosis Numerous affected joints

Foot joint involvement

Subcutaneous nodules

Extra-articular

involvement

Persistent disease

Early functional decline

High ESR/CRP

High RF/anti-CCP titer

Joint space narrowing and

erosions

HLA DR1 or DR4,

particularly DR41

Shared epitope

ACR 2012 Update Presence of 1 or more of:

Functional limitation Extraarticular menifestations:

rheumatoid nodules

Rheumatoid vasculitis

Felty’s syndrome

Positive RF or anti–CCP ab Bony erosions by X-ray

Parameter Mild Moderate Severe

Inflamed joint count

3 to 5 6 to 20 >20

Extraarticular disease

absent absent present

RF/anti-CCP negative positive positive

Joint X-ray normal ST swelling, osteopenia

Narrowing erosion

2012 Update

DAS 28 CDAI

Remission <2.6 <2.8

Low 2.6-3.2 2.8-10

Moderate 3.2-5.1 10-22

Severe >5.1 >22

Tools of Management

Doctor-patient relation

Patient education

Drugs

Rest & physical measures

Surgery

Rehabilitation

Doctor-Patient Relationship

Professionalism

Humanism

Ethics

Quality of care Evidence-based approach

Total care: horizontal All aspects of RA Associated morbidities Unassociated morbidities

Continuity of care Monitoring & treatment readjustment Avoidance of abandonment

Putting CPD info in practice

Patient Education…

Pathophysiology of the disease

Natural course and outcome

Reassurance

by itself not a lethal disease

control of pain & prevention of

disability possible

Patient Education

Scope & limitations of therapeutic options control of pain & disease process not ablative drug toxicity

Need for long-term adherence & follow up Lifestyle modifications

Drugs

DMARDs Conventional

Biologics

NSAIDs

Steroids

Analgesics

PPIs

Anti-resorptives

Other antidotes

Anti-depressants

NSAIDs

Suppress pain, do not control cartilage damage

Response builds up slowly

Don’t combine two NSAIDs

Analgesics

Paracetamol, tramadol

Adjuvant

Conventional DMARDs

Old Gold salts Penicillamine Antimalarials Azathioprine Cyclophosphamid

e Chlorambucil

New Methotrexate Sulphasalazine Leflunomide Cyclosporin Tacrolimus Bucillamine Mizoribine

Major Classes of Biologics..

Anti-TNF-α Etanercept: synthetic soluble TNF receptor-

Fc fusion protein Infliximab: chimeric human-murine anti-TNF-

α Ab Adalumimab: human anti-TNF-α Ab Certolizumab: anti-TNF FAb

fragment+polyethylene glycol Anti-interleukins

Anti-IL1 – Anakinra Anti-IL6 – Tocilizumab

Major Classes of Biologics

Anti-CD 20 (B cell) – Rituximab, ocrelizumab

Anti-CTLA4 Ig – Abatacept, ipilimumab Anti-adhesion molecule Abs: anti-ICAM1,

anti-integrin Anti-CD22 Anti-lymphostat B

DMARDs

Reduce need for NSAIDs

Prevent progression of joint damage

All RA patients should receive some DMARD

Steroids

Adds to pain relief

Adds to control of articular damage

Factors Influencing Choice of Therapy

Activity & severity of disease

History of efficacy & tolerability

Patient preference

Family size and prospects of pregnancy

Socio-economic factors

Financial resources

Distance

Level of education

Prospect of Childbearing Safer NSAIDs (avoid in 3rd trimester)

Ibuprofen, naproxen (+lactation)

Diclofenac, ketoprofen

Safer DMARDs

SSZ (avoid in full term)

CQ/HCQ (under trial C to B)

Azathioprine (in C category)

Steroid

Prednisone

Prednisolone (in C category)

Mild disease

NSAIDs + CQ/HCQ/SSZ

SSZ in women with childbearing potential

Moderate disease

NSAID+MTX/SSZPred

Severe disease

NSAID+MTX+SSZ/Leflu+ 2.5 to 10 mg Pred

How Do We Start?

Immunization

4. Monitoring

Disease response

Drug toxicity

Core Set of Outcome Measures

Tender joint count

Swollen joint count

Intensity of pain (VAS)

Patient’s global assessment

Physician’s global assessment

Physical disability (HAQ)

Acute phase reactants (ESR, CRP)

Measures Usable in Internist Practice

Tender/swollen joint count

Patient’s assessment of pain on VAS

Physician’s global assessment

DAS 28/CDAI

Monitoring for Drug Toxicity

Drug Clinical tools Lab tools

MTX Fever, bleeding, nausea, dyspnea

CBC, platelet, AST, SCr at 4 to 8 weeks

SSZ Fever, bleeding, nausea, rash

CBC: 2 to 4 wks X 3mo, then at 3 mo

Leflu- nomide

Nausea, rash, Diarrhea, alopecia, BP

CBC, ALT: monthly for 6 months, then 2 mo

D-Penici- llamine

Fever, bleeding, rash, edema

CBC, urine protein: 2 wks till stable dose, then 1 to 3mo

Monitoring for Drug Toxicity

Drug Clinical tools Lab tools

NSAIDs Dyspepsia, nausea, abdominal pain

Yearly CBC, ALT, Creatinine

Steroids BP, polyuria, polydipsia, wt. gain

Annual urine sugar

CQ/HCQ Nausea, ophthalmic screening yearly

----

Readjustment of Treatment

Readjustment

Increase the dose

Decrease the dose

Stop the toxic or ineffective drug

Start a new drug

Minimize toxicity

Maximize efficacy

Titration of Therapy -- for Pain Relief

Titrate against Efficacy &

Toxicity

Introduce NSAID

wait 2 to 4 wks

No response-switch to one with higher efficacy,

or add analgesic

wait 2 to 4 wks

If no response add 2.5 to 7.5 mg Pred

Titration of Therapy -- for Disease Control

Titrate against Efficacy & Toxicity

Introduce first DMARD (MTX or SSZ)

Build up the dose

till toxicity supervenes highest recommended dose reached remission obtained

In case of MTX Initiate with 10 to 15 mg Follow up intervals: 2 to 6 weeks Maximum dose 30 mg/wk

Titration of Therapy -- for Disease Control

Titrate against Efficacy & Toxicity

If no response in 3 to 4 months, substitute with another DMARD

If partial remission in 3 to 4 mo, or if the 1st drug was MTX, add a 2nd DMARD

Add a third DMARD, if, after further 3 to 4 months, there is definite but partial response: decrease of

VAS

PGA

DAS 28/CDAI

Full

Remission

& Weaning

Gradually taper off the NSAID

If no relapse, slowly taper off prednisolone, if given

If no relapse, very slowly reduce the dose of DMARD

to the lowest recommended dose

Maintain for years

Full Remission Is Not Common!

Patients often do not tolerate higher doses

of DMARDS

Changes in lab markers of drug toxicity

are frequent

Majority belongs to poor prognosis group

Full Remission Is Not Common!

Do not feel frustrated

Do not frustrate the patient by substantiating her false expectation

To the patient, reiterate the benefit already obtained

Reduction of NSAID

Lesser progression of deformities

Continue DMARDs & NSAIDs/LDGC

Concluding Remarks

Don’t give DMARDs to patients with OA or FM

Don’t prescribe DMARDs for fixed months

Don’t stop DMARDs prematurely

Don’t prescribe gonadotoxic or teratogenic

drugs to patients with incomplete family

except in desperation

Don’t make the follow-up a casual one

Don’t change NSAIDs impatiently

Don’t overuse or under-use steroids

Don’t leave the patient uneducated or

unmotivated

A matter of long-term commitment

Due consideration to drug toxicity

Cost-effective strategy with appropriate

concern for resources of the patient

Efficient doctor-patient rapport