Symptomatic Sarcoidosis

Baughman RP, Barney JB, O’Hare L, Lower EE —Respiratory Medicine, 2016

Acthar Gel was evaluated in patients with progressive symptomatic sarcoidosis in one or more organs1

A retrospective chart review of 47 patients who failed usual therapy because of progressive, symptomatic disease, and despite immunosuppressive therapy and/or excessive toxicity with current treatment1

  • Inclusion criteria for patients in the study were:
    • Diagnosis with sarcoidosis based on standard criteria
    • Incomplete response to current sarcoidosis treatment on ≥1 systemic therapy prior to initiation with Acthar Gel
    • Current or past corticosteroid treatment
    • Current and past therapy included: glucocorticoids, methotrexate, azathioprine, leflunomide, mycophenolate, hydroxychloroquine, thalidomide, infliximab, adalimumab, rituximab
  • Most patients were seeking another treatment option due to current or previous glucocorticoid toxicity
  • All patients received one dose of Acthar Gel therapy (80 U intramuscular or subcutaneous) twice a week, with ≥6 months of post-treatment follow-up
    • Twenty-nine patients were treated for at least 6 months. These patients were treated for a median of 274 days (range 180-609 days)
    • Twenty-one patients were treated for more than 6 months

Treatment Duration

Initiation
N=47
≤3 months
N=29
Clinical outcomes evaluated and therapy continued 
N=18
Clinical outcomes evaluated for patients who discontinued
≥3 months
N=29
Clinical outcomes evaluated 
Initiation ≤3 months ≥3 months
N=47 N=29
Clinical outcomes evaluated and therapy continued
N=29
Clinical outcomes evaluated 
N=18
Clinical outcomes evaluated for patients who discontinued
 

Patient Characteristics

Patients had multi-organ involvement, and most were on multiple concomitant therapies

Age
Range: 20-70 years
Median: 51 years
Lung involvement
81%
Extrapulmonary involvement

Central Nervous System (30%)
Skin (21%)
Eye (15%)

Age Lung involvement Extrapulmonary involvement

Range: 20-70 years
Median: 51 years

81%

Central Nervous System (30%)
Skin (21%)
Eye (15%)

Current and Past Sarcoidosis Treatments at Initiation of Acthar Gel 

  Treated for ≥3 months
  Current Past
Glucocorticoids 27 2
Methotrexate 10 7
Azathioprine 7 4
Leflunomide 4 0
Mycophenolate 0 0
Hydroxychloroquine 5 0
Thalidomide 0 3
Infliximab 7 4
Adalimumab 1 0
Rituximab 2 0
  Treated for <3 months
  Current Past
Glucocorticoids 18 0
Methotrexate 5 4
Azathioprine 4 1
Leflunomide 1 0
Mycophenolate 1 0
Hydroxychloroquine 1 1
Thalidomide 0 1
Infliximab 1 2
Adalimumab 2 0
Rituximab 2 0
  Total
  Current Past
Glucocorticoids 45 2
Methotrexate 15 11
Azathioprine 11 5
Leflunomide 5 0
Mycophenolate 1 0
Hydroxychloroquine 6 1
Thalidomide 0 4
Infliximab 8 6
Adalimumab 3 0
Rituximab 4 0
  Treated for ≥3 months Treated for <3 months Total
  Current Past Current Past Current Past
Glucocorticoids 27 2 18 0 45 2
Methotrexate 10 7 5 4 15 11
Azathioprine 7 4 4 1 11 5
Leflunomide 4 0 1 0 5 0
Mycophenolate 0 0 1 0 1 0
Hydroxychloroquine 5 0 1 1 6 1
Thalidomide 0 3 0 1 0 4
Infliximab 7 4 1 2 8 6
Adalimumab 1 0 2 0 3 0
Rituximab 2 0 2 0 4 0

Clinical outcomes for sarcoidosis patients who were treated for ≥3 months (n=29) were evaluated either as improved, stable, or relapsed

Improved
  • Reduced inflammation by chest imaging or PET scanning
  • >10% improvement in forced vital capacity (FVC)
  • >50% improvement of skin lesion(s) or central nervous system (CNS) lesions on magnetic resonance imaging
  • >50% reduction in use of topical glucocorticoids for ocular disease
  • Normalization and/or 50% reduction of liver or serum calcium abnormalities
Stable
  • No clinically significant change in target organ, but reduction in dosage of glucocorticoids
Relapsed
  • Worsening of target organ when prednisone was reduced, and patient had to be maintained on initial or higher dose of glucocorticoids
Improved Stable Relapsed
  • Reduced inflammation by chest imaging or PET scanning
  • >10% improvement in forced vital capacity (FVC)
  • >50% improvement of skin lesion(s) or central nervous system (CNS) lesions on magnetic resonance imaging
  • >50% reduction in use of topical glucocorticoids for ocular disease
  • Normalization and/or 50% reduction of liver or serum calcium abnormalities
  • No clinically significant change in target organ, but reduction in dosage of glucocorticoids
  • Worsening of target organ when prednisone was reduced, and patient had to be maintained on initial or higher dose of glucocorticoids

Study Limitations

These results are based on a retrospective chart review of 47 patients being treated with Acthar Gel. There was no placebo control and the assessment of response was subjective. Results may not be fully representative of outcomes in the overall patient population. All 47 patients were receiving multiple therapies. The clinical outcomes may not be solely attributable to Acthar Gel.

93% (n=27) of patients treated for ≥3 months with Acthar Gel had an improved or stable target organ response1

Primary Target Organ Response After ≥3 Months of Acthar Gel Treatment (n=29)

 

*Reduced inflammation, >10% improvement in FVC, >50% reduction in use of topical glucocorticoids, or improvement in other organ abnormalities.

No clinically significant change in target organ, but reduction in dosage of glucocorticoids.

Worsening of target organ when prednisone was reduced and patient had to be maintained on initial or higher dose of glucocorticoids.

Improved or Stable Response by Primary Target Organ in Patients Who Completed 3 Months of Acthar Gel Treatment

Lungs response with Acthar Gel statistic icon CNS response with Acthar Gel statistic icon Skin response with Acthar Gel statistic icon Eyes response with Acthar Gel statistic icon

Safety Findings

18 of 47 patients discontinued treatment due to:

  • Death (n=2)
    • Death was attributed to the progression of sarcoidosis, not to Acthar Gel therapy
  • Anxiety/agitation (n=3)
  • Peripheral edema (n=2)
  • Weakness (n=1)
  • Injection site allergic reaction (n=1)
  • Cost (n=4)
  • Cryptococcal infection (n=2)
  • Injection site pain (n=1)
  • Worsening disease (n=1)
  • Noncompliance (n=1)

Adverse events

  • The most commonly observed adverse events included peripheral edema or agitation (11 of 47). Six of these patients treated for ≥3 months were able to continue after the drug was reduced to 40 IU once to twice a week
  • One patient experienced skin hyperpigmentation

23 of 47 patients treated with Acthar Gel were being treated for diabetes; 33 were on treatment for systemic hypertension

  • Upon review, there was no significant increase of treatment for either diabetes or hypertension