dmpm management
TRANSCRIPT
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.