Rheumatoid Arthritis (RA)

Gillis T, Crane M, Hinkle C, and Wei N —Open Access Rheumatology, 2017

Acthar Gel was evaluated in patients with active disease and had been previously treated with ≥3 therapeutic agents with a different MOA¹

Study Design

Results

STUDY OBJECTIVE

An open-label, interventional, single-group study of 8 patients with refractory and active RA¹

Refractory disease defined as treated with 3 therapeutic agents with a different mechanism of action (MOA) for more than 3 months
Active disease defined as 6 tender and 6 swollen joints
Patients received Acthar Gel 80 U twice weekly via subcutaneous injection over 12 weeks

Patient Characteristics

Mean age	Mean disease duration
64.6	20.9 years
Previous treatments
Tofacitinib citrate Certolizumab pegol Abatacept Etanercept Hydroxychloroquine Adalimumab Tocilizumab
Concomitant treatments*
Certolizumab pegol Methotrexate Prednisone Morphine sulfur Cyclobenzaprine Acetaminophen Hydromorphone Abatacept Celecoxib Meloxicam Etanercept Rituximab Tofacitinib citrate
Mean tender joint count (baseline)	Mean swollen joint count (baseline)
31.4	31

Mean age	Mean disease duration	Previous treatments	Concomitant treatments*	Mean tender joint count (baseline)	Mean swollen joint count (baseline)
64.6	20.9 years	Tofacitinib citrate Certolizumab pegol Abatacept Etanercept Hydroxychloroquine Adalimumab Tocilizumab	Certolizumab pegol Methotrexate Prednisone Morphine sulfur Cyclobenzaprine Acetaminophen Hydromorphone Abatacept Celecoxib Meloxicam Etanercept Rituximab Tofacitinib citrate	31.4	31

^*Not every patient was on the same concomitant treatments.

Study Assessments

Primary endpoint measures included the Ritchie-Camp Articular (RCA) Index and 20-item Health Assessment Questionnaire^† (HAQ) scores prior to treatment and at 2- to 4-week intervals
Secondary endpoint measures included acute erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels

^†Health Assessment Questionnaire assesses patient outcomes in 4 domains: disability, discomfort and pain, drug side effects, and cost. It includes 8 sections—dressing, arising, eating, walking, hygiene, reach, grip, and common activities.

Study Limitations

This was a small study with only 8 patients and no comparator arm
Sample bias may exist since this was an open-label trial and patients and physicians were aware that they were receiving Acthar Gel
The results of the study cannot be solely attributable to Acthar Gel since patients were on different medications at the start of the trial and no washout periods or standardization of concomitant medications were undertaken
Acthar Gel has not been formally studied in combination with other treatments

Clinical characteristics at baseline and at week 12 of Acthar Gel treatment

Characteristics	Baseline	At Week 12	P value
Tender joint count			.0047
Mean (SD)	31.4 (16.3)	10.9 (9.1)
Median	33.5	9.0
Range	7–50	0–26
Swollen joint count			.0004
Mean (SD)	32.9 (10.74)	20.8 (9.6)
Median	36	20.8
Range	17–48	6–37
HAQ score			.1249
Mean (SD)	1.78 (0.71)	1.4 (0.76)
Median	1.75	1.3
Range	0.875–2.75	0.38–2.5
ESR (mm/h)			.8996
Mean (SD)	21.5 (16.5)	17.3 (10.3)
Median	16	16.0
Range	7–60	5–32
CRP (mg/L)			.4776
Mean (SD)	0.825 (0.6)	1.0 (1.3)
Median	0.9	0.45
Range	0.1–1.8	0.1–3.8
Patient VAS			.0220
Mean (SD)	40.1 (30.3)	16.9 (14.8)
Median	28.5	17
Range	8–97	1–40
Physician VAS			.0002
Mean (SD)	7.6 (2.2)	2.9 (2.2)
Median	8.4	2.5
Range	3.8–9.9	0.30–6.5
DAS28			.0032
Mean (SD)	5.7 (0.84)	3.8 (1.2)
Median	5.83	3.4
Range	4.33–6.87	2.5–5.6

Characteristics	Baseline	At Week 12	P value
Tender joint count			.0047
Mean (SD)	31.4 (16.3)	10.9 (9.1)
Median	33.5	9.0
Range	7–50	0–26
Swollen joint count			.0004
Mean (SD)	32.9 (10.74)	20.8 (9.6)
Median	36	20.8
Range	17–48	6–37
HAQ score			.1249
Mean (SD)	1.78 (0.71)	1.4 (0.76)
Median	1.75	1.3
Range	0.875–2.75	0.38–2.5
ESR (mm/h)			.8996
Mean (SD)	21.5 (16.5)	17.3 (10.3)
Median	16	16.0
Range	7–60	5–32
CRP (mg/L)			.4776
Mean (SD)	0.825 (0.6)	1.0 (1.3)
Median	0.9	0.45
Range	0.1–1.8	0.1–3.8
Patient VAS			.0220
Mean (SD)	40.1 (30.3)	16.9 (14.8)
Median	28.5	17
Range	8–97	0–40
Physician VAS			.0002
Mean (SD)	7.6 (2.2)	2.9 (2.2)
Median	8.4	2.5
Range	3.8–9.9	0.30–6.5
DAS28			.0032
Mean (SD)	5.7 (0.84)	3.8 (1.2)
Median	5.83	3.4
Range	4.33–6.87	2.5–5.6

When Acthar Gel therapy was stopped, all improvements gained during the study period were lost by week 16

Safety Findings

Investigators reported that the majority of adverse events reported were mild and resolved and/or were unrelated to Acthar Gel.

Patients who experienced an adverse event	10
Adverse event
Reaction at injection site	1
Hypoglycemia	1
Hip pain	1
Development of allergies	1
Pneumonia	1
Atrial fibrillation	1
Fibromyalgia	1
Hypertension	1
Serious adverse event
Pulmonary embolism	1
Deep vein thrombosis	1

Patients who experienced an adverse event	10
Adverse event
Reaction at injection site	1
Hypoglycemia	1
Hip pain	1
Development of allergies	1
Pneumonia	1
Atrial fibrillation	1
Fibromyalgia	1
Hypertension	1
Serious adverse event
Pulmonary embolism	1
Deep vein thrombosis	1

CRP=C-reactive protein. DAS28=disease activity score-28. ESR=erythrocyte sedimentation rate. HAQ=health assessment questionnaire. SD=standard deviation. VAS=visual analog scale.

NEXT: Retrospective Case Studies (Brown et al 2015)

References

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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 active disease and had been previously treated with ≥3 therapeutic agents with a different MOA1

STUDY OBJECTIVE

An open-label, interventional, single-group study of 8 patients with refractory and active RA1

Patient Characteristics

Study Assessments

Study Limitations

Clinical characteristics at baseline and at week 12 of Acthar Gel treatment

Safety Findings

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IMPORTANT SAFETY INFORMATION

Contraindications

INDICATIONS

IMPORTANT SAFETY INFORMATION

Contraindications

INDICATIONS

Warnings and Precautions

Adverse Reactions

Acthar Gel was evaluated in patients with active disease and had been previously treated with ≥3 therapeutic agents with a different MOA¹

An open-label, interventional, single-group study of 8 patients with refractory and active RA¹