Management of

Polymyositis & Dermatomyositis

Ruling Out Associated Malignancy

• Old age >65

• Dermatomyositis compared with PM

• Cutaneous necrosis on the trunk

• Cutaneous leukocytoclastic vasculitis

• Capillary damage on muscle biopsy

Five-year Survival

• 1971-85: 52-65%

• 2001-06: 75-95%

Causes of Death

Infection

Respiratory failure

Cardiovascular disease

Malignancies

Predictors of Outcome• Delay in the initiation of treatment >6 mo

• Severe weakness at presentation

• Dysphagia

• Respiratory muscle weakness

• DPLD

• Associated malignancy

• Cardiac involvement

• ? Old age

Response to GC

• DM: Initial 87%

– 92% flared during tapering

• Myositis overlap: 87-100%

• PM: 50%

Response Patterns….

• Responsive to initial therapy and achieve

sustained disease control

– off all therapy

– with low dose maintenance therapy

Response Patterns

• Recurrent disease: after achieving control,

experience recurrences (flares) during or

after medication tapering

• Resistant disease: does not respond

– alternative approaches must be considered

Course of Treated Disease

• Chronic – 60%

• Polycyclic – 20%

• Monocyclic 20%Bronner IM et al. Ann Rheum Dis 2006; 65: 1456-61

Goals of Treatment

• To improve muscle strength

• To avoid the development of

extra-muscular complications

• In DM, resolution of skin

manifestations

• To improve QoL

General Principles

• Establish disease control:

– high doses for first several months

• Slow taper to lowest effective dose

– total duration between 9 and 12 months

Initial GC therapy

• Prednisone 1 mg/kg/day maximum daily dose of 80 mg

• PMP 1000 mg/dX3 d at the start of therapy– Bedridden

– Respiratory failure

– Dysphagia

GC Taper

• Should begin after (4-) six weeks

• Insufficient clinical improvement

– Addition of a SSA if not begun with GC

A Standard Protocol…

• By 10 mg each week up to 40 mg/day

– 8 wk

• By 5 mg each week up to 20 mg/day

– 12 wk

• By 2.5 mg each week up to 10 mg/day

– 16 wk

A Standard Protocol• By 1 mg every two weeks → 5 mg/day

– 26 wks

• Continuation of taper– if good disease control achieved and

maintained

• Further taper should not proceed > 1 mg decreases every two weeks

Initiation

• Simultaneously with pred

• Mandatory:– No improvement with pred over 4 to 6 weeks– Profound weakness– Significant extramuscular involvement:

• ILD• Dysphagia

MTX-Dosing

• Started with 15 mg/wk

– increasing weekly by 5mg/wk up to 25 mg/wk

• If improvement at 4 wk unsatisfactory

– Inj 25 mg/wk→ 30 mg → 37.5 mg/wk → ? 50

– Titrating carefully against toxicity

MTX-Prevention of Toxicity

• Folic acid 1 mg/d except MTX day

• Folinic acid 5 mg:

– MTX >25 mg/wk

– AEs not adequately prevented with folic acid

Preferential Indications for AZT

ILD

Liver disease

Unwillingness to stop alcohol

AZT • 50 mg/d X 1 wk

– Increased progressively to 1.5 to 3 mg/kg/d

– Usual maximum 200 mg

• CBC and ALT monthly initially, then 3 monthly

• Thiopurine methyltransferase (TMPT):

– Predictor of marrow suppression

– Low dose for hetero, avoided in homozygous

MonitoringDisease response

Drug toxicity

Intervals for Outpatient

• Weekly for 2 wks

• Fortnightly for 4 wks

• Monthly for 3 months

• Then at 2 to 3 mo intervals

Tools

• Customized history• Customized examination• Lab tests:

– CBC– ALT– S creatinine (if on MTX)– CPK– CXR (less frequently)

Response to Treatment

• Assessed by:– Improvement of muscle strength– Resolution of skin lesions

• Rate:– Rapid: within several week– Slow: progress not evident > 3 mo

Muscle Strength Vs. Enzymes

• Muscle strength is a more reliable indicator of clinical progress than muscle enzymes

• Serum enzymes fall within two weeks, but normalization takes considerably longer– Adjusting prednisone doses in attempts to

normalize muscle enzyme concentration may lead to over-treatment

Muscle Testing• Quadriceps - crosses arms and rises from a chair, using

only the proximal leg muscles

• Hip flexors - lifts leg off the table while lying down without bending the knees

• Deltoids - extend the arms against the examiner's pressure with flexed elbow

• Neck flexors - pushes head forward while the examiner applies reverse pressure against the forehead

• ? Vital capacity

Other Monitoring Parameters

• Carefully during the tapering period:

– Recurrent weakness

• steroid myopathy also affects the proximal

– Extramuscular complications of DM or PM

– Features of drug toxicity

Recurrent Disease

• Definition: recurrences (flares) during or after medication tapering after full control

• Flare patterns:

–at > 10 mg/day prednisone

–at ≤10 mg/day prednisone

–off prednisone but on SSA–off all immunosuppressives

1. Flare At > 10 mg/day Prednisone

• Prednisone, 1 mg/kg per day, to reestablish

disease control

• Addition of a SSA if neither has been used

• Treatment of the flare as resistant disease if

the patient is already taking SSA

– Usual course in our situation

2. Flare At ≤10 mg/day Prednisone

• pred to lowest dose to reestablish control– The dose is based on severity of clinical findings

– If flare detected early, dose may be < 1 mg/kg/d (? 0.5 mg/kg)

– Minimum re-induction dose is 20 mg/day

• Increase AZT/MTX to a higher dose, if the dose

has not already been maximized

• Once control restored, taper slower than initial– maintained on low dose prednisone (e.g., 5 mg/day) for ≥ 1 year

3. Flare off Pred but on SSA….

• Prednisone reinstituted at lowest dose to

reestablish control

– The dose selected on severity of clinical

findings

– May be ≤ 1 mg/kg (? 0.5 mg/kg) if flare

detected early

– Usual minimum -- 20 mg/day

Flare off Pred but on SSA

• SSA changed from MTX to AZT or vice

versa

• If treated previously with both MTX and

AZT, flare regarded as a manifestation of

resistance

4. Flare Off All Immunosuppressives

• Prednisone should be reinstituted

– Dose varying with the severity of the relapse

• The minimum starting dose is 20 mg/day

• A SSA should be resumed

Definition

• No (or minimal) response after 6

(?4) weeks

Apparent Failure

• Misdiagnoses: IBM, dystrophies, metabolic

• GC myopathy: lower pred dose

• Associated malignancy

Options for Resistant Disease• Rituximab

• IVIG

• MTX higher (>25 mg) doses and parenteral

• Combination of AZT & MTX

• Calcineurin inhibitors: cyclosporine, tacrolimus

• MMF

• Cyclophosphamide

• TNF inhibitors

General Measures

Education

Exercises

Prophylaxis against infections

Prevention of GIOP

Prevention of aspiration

Avoidance of UV light

Physical Therapy and Rehabilitation…

• Should begin early in course of treatment:

– regimens tailored to the severity of weakness

• Even during active disease, appropriate

exercise programs do not

– increase serum CK levels

– delay recovery of muscle strength

Physical Therapy and Rehabilitation…

• Bed or chair-bound patients: passive range of

motion exercises to prevent joint contractures

– Careful attention to positioning reduces the

risk of pressure sores

• Isometric and resistive exercises: as soon as the

patient has recovered strength to be able to

participate

Physical Therapy and Rehabilitation

• Patients with less severe weakness: participate

in an active exercise program

– progressing as tolerated from lower level

isometric exercises to more vigorous isotonic

exercises

• Patients with mild weakness: continue

reasonable levels of activity as tolerated

Prevention of Infections• Vaccinations:

– Pneumococcus– Influenza virus– Hepatitis B– ? Hemophilus influenzae B

• Pneumocystis jirovecii prophylaxis– Cotrimoxazole double strength once daily– If MTX being used, single strength

Skin Care• Sun protection

– Sunscreens

– Sun protective clothing

– Minimizing sun exposure

• Anti-malarials

• Prevention of sores

• Keeping skin dry and clean

• Pruritus: hydroxyzine, topical menthol, camphor etc.

Prevention of Osteoporosis…

• Exercises as permitted

• Calcium and vitamin D: for patients

receiving pred ≥5 mg daily for ≥3 months

– 1200 mg of elemental calcium total diet plus

supplement

– 800 IU of vitamin D daily

Prevention of Osteoporosis

• Postmenopausal women & men at high

risk for fracture (elderly, prior fragility

fracture): oral bisphosphonate

– alendronate 35 mg/week for prevention, 70

mg/week for treatment

– risedronate 35 mg/week

Final Weaning….

• Pred 5 mg/d continued for 1 to 3 mo

– 12 mo in resistant disease or HO flare

• Tapered by 1mg at 2 to 4 wk intervals to

complete withdrawal at 2 to 4 mo

Final Weaning

• Taper of MTX/AZT started if remission maintained for 3 to 12 (for resistant & flared) mo off steroid– Tapered at monthly intervals to complete

withdrawal after six months if no relapse• unsuccessful in majority

– Careful assessment for signs of relapse

Duration of Treatment

• Minimum duration:

– Pred 9 mo.

– MTX/AZT 18 mo

– Successful in 20%

• Maximum duration: indefinite

– 41% were using >10 mg pred or other immunosuppressive after 5 years

Bronner IM et al. Ann Rheum Dis. 2006 Nov;65(11):1456-61.