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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