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

Study Design

Results

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=47	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)

Primary target organ response in patients treated with Acthar Gel chart

^*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

Lung response in patients treated with Acthar Gel statistic icon CNS response in patients treated with Acthar Gel statistic icon Skin response in patients treated with Acthar Gel statistic icon Eye response in patients treated 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

NEXT: Pulmonary Sarcoidosis Case Study (Baughman et al 2016)

References

Explore the potential MOA of Acthar Gel

Learn more

Learn about at-home injection training for Acthar Gel patients

Learn more

IMPORTANT SAFETY INFORMATION

Contraindications

Acthar should never be administered intravenously
Administration of live or live attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of Acthar
Acthar is contraindicated where congenital infections are suspected in infants
Acthar is contraindicated in patients with scleroderma, osteoporosis, systemic fungal infections, ocular herpes simplex, recent surgery, history of or the presence of a peptic ulcer, congestive heart failure, uncontrolled hypertension, primary adrenocortical insufficiency, adrenocortical hyperfunction, or sensitivity to proteins of porcine origin

INDICATIONS

Acthar^® Gel (repository corticotropin injection) is indicated for:

Treatment during an exacerbation or as maintenance therapy in selected cases of systemic lupus erythematosus
Treatment during an exacerbation or as maintenance therapy in selected cases of dermatomyositis (polymyositis)
Adjunctive therapy for short-term administration (to tide the patient over an acute episode or exacerbation) in: psoriatic arthritis; rheumatoid arthritis, including juvenile rheumatoid arthritis (selected cases may require low-dose maintenance therapy); ankylosing spondylitis
Treatment of symptomatic sarcoidosis

Warnings and Precautions

The adverse effects of Acthar are related primarily to its steroidogenic effects
Acthar may increase susceptibility to new infection or reactivation of latent infections
Suppression of the hypothalamic-pituitary-adrenal (HPA) axis may occur following prolonged therapy with the potential for adrenal insufficiency after withdrawal of the medication. Adrenal insufficiency may be minimized by tapering of the dose when discontinuing treatment. During recovery of the adrenal gland patients should be protected from the stress (e.g. trauma or surgery) by the use of corticosteroids. Monitor patients for effects of HPA suppression after stopping treatment
Cushing’s syndrome may occur during therapy but generally resolves after therapy is stopped. Monitor patients for signs and symptoms
Acthar can cause elevation of blood pressure, salt and water retention, and hypokalemia. Blood pressure, sodium, and potassium levels may need to be monitored
Acthar often acts by masking symptoms of other diseases/disorders. Monitor patients carefully during and for a period following discontinuation of therapy
Acthar can cause GI bleeding and gastric ulcer. There is also an increased risk for perforation in patients with certain gastrointestinal disorders. Monitor for signs of bleeding
Acthar may be associated with central nervous system effects ranging from euphoria, insomnia, irritability, mood swings, personality changes, and severe depression to psychosis. Existing conditions may be aggravated
Patients with comorbid disease may have that disease worsened. Caution should be used when prescribing Acthar in patients with diabetes and myasthenia gravis
Prolonged use of Acthar may produce cataracts, glaucoma, and secondary ocular infections. Monitor for signs and symptoms
Acthar is immunogenic and prolonged administration of Acthar may increase the risk of hypersensitivity reactions. Neutralizing antibodies with chronic administration may lead to loss of endogenous ACTH activity
There is an enhanced effect in patients with hypothyroidism and in those with cirrhosis of the liver
Long-term use may have negative effects on growth and physical development in children. Monitor pediatric patients
Decrease in bone density may occur. Bone density should be monitored for patients on long-term therapy
Pregnancy Class C: Acthar has been shown to have an embryocidal effect and should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus

Adverse Reactions

Common adverse reactions for Acthar are similar to those of corticosteroids and include fluid retention, alteration in glucose tolerance, elevation in blood pressure, behavioral and mood changes, increased appetite, and weight gain
Specific adverse reactions reported in IS clinical trials in infants and children under 2 years of age included: infection, hypertension, irritability, Cushingoid symptoms, constipation, diarrhea, vomiting, pyrexia, weight gain, increased appetite, decreased appetite, nasal congestion, acne, rash, and cardiac hypertrophy. Convulsions were also reported, but these may actually be occurring because some IS patients progress to other forms of seizures and IS sometimes masks other seizures, which become visible once the clinical spasms from IS resolve

Other adverse events reported are included in the full Prescribing Information.

Please see full Prescribing Information for additional Important Safety Information.

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

Treatment Duration

Patient Characteristics

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

Current and Past Sarcoidosis Treatments at Initiation of Acthar Gel

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

Study Limitations

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)

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

Safety Findings

Adverse events

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

You might also like

IMPORTANT SAFETY INFORMATION

Contraindications

INDICATIONS

IMPORTANT SAFETY INFORMATION

Contraindications

INDICATIONS

Warnings and Precautions

Adverse Reactions

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

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