fatigue in sarcoidosis - cleveland clinic · “chemobrain” in adult cancer patients e. lower1,...
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Fatigue in Sarcoidosis
Elyse E. Lower, M.D.
Sarcoidosis & Interstitial Lung Disease Clinic
University of Cincinnati
Fatigue in Sarcoidosis
• Up to 80% of patients with sarcoidosis report fatigue
• Fatigued patients report worse Quality of Life
• Many sarcoidosis patients with good control of disease still have persistent, disabling fatigue
Fatigue
Vermoeidheid
Fatica Yтомление
Fatiga Yorgunluk
Ermüdung
épuisement
疲労 疲勞,勞累
замор
What is Fatigue?
• Temporary loss of strength and energy
• Tiredness
• Exhaustion
• Lethargy
• Weariness
Fatigue: transient or self-limiting
• Viral or other infection
• Overwork
• Stress
• Sleep deprivation
• Jet-leg
Listen to the signals of your body Take a nap on time…
Vincent van Gogh
What Causes Fatigue?
Diabetes
Thyroid Disease
Anemia
Impaired Mobility: Heart or Lung Disease, Arthritis
Sleep Disorders
Poor Nutrition
Recurrent Infections
Depression
Assessment of Fatigue
Fatigue Intervention: Disease Control
• Treatment can be a double-edged sword.
• Sarcoid granulomas may worsen fatigue.
• However, treatment with corticosteroids may lead to side effects that worsen fatigue. – Weight gain
– Diabetes
– Sleep apnea
Assessment of Fatigue
Additional Fatigue Intervention
• Lifestyle changes– Exercise
– Diet
– Weight reduction
Persistent Fatigue: Sarcoidosis Associated Fatigue
Fatigue Assessment Instrument
Pitfalls for Studying Fatigue
• Measuring fatigue is difficult
• Placebo effect is powerful
• Fatigue varies from person to person
Measuring Fatigue
• Multiple instruments to measure QOL and fatigue
• No perfect testing
• Chronic Illness– FACIT-F, SF-36
– WHO-QOL
• Sarcoidosis – Fatigue Assessment Scale (FAS)
Neurostimulant Therapy for Sarcoid Associated Fatigue
• Case reports suggest benefit for methylphenidate (Ritalin®) for chronic sarcoidosis patients with persistent fatigue.
• Other neurostimulants, including dex-methylphenidate (Focalin®), can improve fatigue in cancer patients with “chemo”brain.
A Phase II, Randomized Placebo-controlled Trial of the Safety and Efficacy of d-MPH as
a New Treatment of Fatigue and
“Chemobrain” in Adult Cancer Patients
E. Lower1, S. Fleishman2, A. Cooper3, J. Zeldis3, H. Faleck3, D. Manning3
1 University of Cincinnati Medical Center, Cincinnati, OH 2 Beth Israel Cancer Center, New York, NY
3 Celgene Corporation, Warren, NJ
Lower EE, J Pain Symptom Manage 2009;38:650-62.
Purpose of Study
• To evaluate the efficacy and safety of dexmethylphenidate (d-MPH, Focalin), a CNS stimulant, for the treatment of fatigue and cognitive impairment associated with chemotherapy
Change in FACIT-F (fatigue) Total Score at Each Week
-14
-12
-10
-8
-6
-4
-2
00 1 2 3 4 5 6 7 8
Treatment Week
Ch
ang
e fr
om
Bas
elin
e
*
* **** **
*** p < 0.05
** p < 0.01
d-MPH d-MPH LOCF PLCBO PLCBO LOCF
LOCF = Last observation carried forward
A Randomized Double Blind, Placebo Controlled Trial of Dexmethylphenidate Hydrochloride (d-MPH) for Sarcoidosis
Associated Fatigue
Elyse E. Lower, MD
Stacy Harman
Robert P. Baughman, MD
University of Cincinnati
Sarcoidosis Interstitial Lung Disease Clinic
Lower EE, Harman S, Baughman RP. Chest 2008; 133:1189-1195.
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
Week of Study
Washin Washout
Treatment 1 Treatment 2
Double Blind, Placebo-Controlled, Cross Over Study
d-MPH d-MPH
Placebo Placebo
Treatment 1: d-MPH or PlaceboTreatment 2: Placebo or d-MPH (opposite of treatment 1)
0
5
10
15
20
25
30
35
40
Baselin
e 1 2 3 4 5 6 7 8
Weeks of Therapy
FA
S S
core
Placebo d-MPH
FAS: Lower Score, Less Fatigue
Difference between d-MPH and placebo p<0.02
0
5
10
15
20
25
30
35
0 1 2 3 4 5 6 7 8
Weeks of Therapy
FA
CIT
-F S
core
Placebo d-MPH
FACIT-F: Higher Score, Less Fatigue
Difference between d-MPH and placebo p<0.005
Sleep Disorders
Why do Neurostimulants Improve Fatigue?
• Sleep problems are common in patients with fatigue
• Methylphenidate is useful in treating excessive sleepiness or narcolepsy
• Armodafinil (Nuvigil®) is also useful in treating excessive daytime somnolence– Assessed by Mean Sleep Latency Time (MSLT)
Armodafinil for Sarcoidosis Associated Fatigue: Double Blind, Placebo Controlled,
Cross Over Trial
• Elyse E Lower, M.D.1, Atul Malhotra, M.D.2, Victoria Surdulescu, M.D.1, Robert P. Baughman, M.D.1– 1 University of Cincinnati
– 2 Cleveland Clinic Foundation
Lower, E. E. et al. J.Pain Symptom.Manage. 2012 e-published
R-Modafinil for Sarcoidosis Associated Fatigue
Study Aims
• Determine if r-modafinil is effective in treating sarcoidosis associated fatigue– Study design similar to d-MPH study
• Determine if r-modafinil is more effective in treating sarcoidosis associated fatigue in patients with excessive daytime somnolence– Determined by Mean Sleep Latency Time (MSLT)
< 8 minutes
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
Week of Study
Washin Washout
Treatment 1 Treatment 2
Double Blind, Placebo-Controlled, Cross Over Study
r-Modafinil r-Modafinil
Placebo Placebo
Treatment 1: r-Modafinil or PlaceboTreatment 2: Placebo or r-Modafinil (opposite of treatment 1)
SleepStudyMSLT
SleepStudyMSLT
ALL PATIENTSChange in FAS score from Baseline
after 8 weeks of therapy, p<0.01
Change in FAS Score from Baseline
Eight Weeks TherapyMSLT > 8 minutes
-30
-20
-10
0
10
20
Placebo Armodafinil
Ch
ang
e F
AS
fro
m
Bas
elin
e
Eight Weeks TherapyMSLT < 8 minutes
-15
-10
-5
0
5
10
Placebo Armodafinil
Ch
ang
e F
AS
fro
m
Bas
elin
e
Red: MSLT <8 minutes; Blue MSLT>8 minutes
Summary of r-Modafinil Study
• r-Modafinil was effective in treating sarcoidosis associated fatigue
• The drug was as effective for patients without hypersomnolence (MSLT>8 minutes) as for those with hypersomnolence (MSLT<8 minutes)
Summary and Conclusions
• Fatigue is a very common problem in sarcoidosis
• Assessment needs to include– Appropriate disease treatment
– Evaluation and treatment of other medical problems
• Persistent fatigue may require intervention with neurostimulants along with lifestyle changes
Thank you
Questions?
Assessment of Fatigue