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

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00 1 2 3 4 5 6 7 8

Treatment Week

Ch

ang

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om

Bas

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*

* **** **

*** 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

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25

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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

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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

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-10

0

10

20

Placebo Armodafinil

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fro

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Eight Weeks TherapyMSLT < 8 minutes

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-10

-5

0

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10

Placebo Armodafinil

Ch

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AS

fro

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Bas

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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