Patient Walks Again After Treatment of Severe, Refractory Dermatomyositis

By Anthony Fernandez, MD, PhD

A 60-year-old woman presents with a severe rash on her face, arms and torso. She had seen physicians near her home in Dayton, Ohio, and was originally diagnosed with sunburn, though she reports not having spent much time in the sun. She felt that her condition continued to deteriorate, with her skin going from “red to violet” and the development of pain in muscles and joints. She came to Cleveland Clinic for a second opinion 11 months following the initial “sunburn” diagnosis. She was diffusely covered in rash and so weak that she was unable to walk.

We suspected dermatomyositis, which can be a challenge to diagnose, as it is often mistaken for lupus, eczema and other conditions. Many clinicians may never see cases like this.

The patient was hospitalized for five days, and was given very high doses of IV steroids, along with azathioprine and hydroxychloroquine. She was discharged home on those medicines plus oral steroids. At follow-up two months later, she showed only marginal improvement in the degree of rash and muscle weakness. She was still far from being adequately controlled. Over the next several months we tried a number of other medications, including mycophenolate mofetil and intravenous immunoglobulin (IVIG). IVIG, especially, added to her improvement. However, after all of those medications she still was not adequately controlled, as significant skin pain and itching persisted. She still had weakness compared to baseline, but we felt her myositis was controlled and weakness was related to previous myositis.

At this point, we enrolled the patient in our open-label trial of adrenocorticotropic hormone (ACTH) gel, which is a respiratory corticotropin injection. In the trial, the patient received twice weekly ACTH injections for six months, in addition to her other current medications.

While her dermatomyositis is not cured, with the addition of ACTH injections we were able to achieve and maintain excellent control. There is no active inflammation in her skin, her muscle strength is normal and we have been able to decrease the amount of systemic medicines she receives. Her quality of life has definitely improved.

Left: Patient in 2015, before treatment. Right: Patient in 2016, after treatment.

Dermatomyositis

Dermatomyositis is a very heterogeneous disease, with an annual incidence of 1 per 100,000, with a peak between the ages of 40 and 50. Dermatomyositis can be quite resistant to treatment, with long-term control frequently difficult to achieve. Symptoms, such as muscle weakness and skin eruptions, can overlap other systemic rheumatic diseases, including systemic lupus erythematosus and systemic sclerosis, among others. Certain patients with MDA-5 antibodies are at higher risk for developing interstitial lung disease. Patients should also be monitored for esophageal disease.

Clinical trials

We are currently enrolling patients in three clinical trials.

NCT03181893: A Phase 2A, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy, Safety and Tolerability of PF-06823859 in Adult Subjects with Dermatomyositis. This is the first medicine specifically designed to treat dermatomyositis.

Inclusion criteria:

• Must have CDASI Activity score of greater than or equal to 14, and have failed at least 1 standard of care systemic treatment, (eg, corticosteroids)
• Confirmation of DM by the investigator and two of the following:
  1. Gottron’s papules
  2. Gottron’s sign
  3. Heliotrope eruption
  4. Nailfold changes, (dilated capillary loops, capillary dropout, cuticular hypertrophy and/or rugged cuticles
  5. Photodistributed violaceous erythema (skin that is exposed to sunlight and appears purplish/reddish, and patchy in appearance)
  6. Positive DM serology
• Post DM diagnosis; standard of care workup for DM must have been completed prior to entry into this research study
• Willing to provide six biopsies during the course of the research study

Exclusion criteria:

• Investigator site staff or members of their family
• Acute and chronic present medical conditions
• Intake of greater than 15 mg of prednisone or equivalent per day
• Pregnant or breastfeeding females, and fertile men and women who will not comply with the use of two effective birth control methods as per the research protocol
• Have required management of acute or chronic infections
• Have pre-existing demyelinating disorder such as multiple sclerosis, or other severe neurological deficits
• Clinically significant lab abnormalities
• Any health condition that may be worsened by immunosuppression

NCT02245841: Efficacy and Safety of H.P. Acthar Gel for the Treatment of Refractory Cutaneous Manifestations of Dermatomyositis. This trial is designed for refractory cutaneous dermatomyositis, which we define as having failed at least two systemic medications typically used to treat dermatomyositis.

Inclusion criteria:

• Must be 18 years of age or older with refractory cutaneous symptoms related to either classic dermatomyositis (CD), juvenile dermatomyositis (JD) or amyopathic dermatomyositis (AD). Diagnosis will be based on either Bohan and Peter criteria (CD and JD) or Sontheimer’s criteria (AD)
• Must have had a skin biopsy with histologic features consistent with dermatomyositis and current cutaneous manifestations consistent with dermatomyositis
• Although not mandatory, patients with evidence of current or previous active myositis will be eligible for enrollment. Patients will be considered to have refractory disease if cutaneous manifestations exist despite treatment with steroids and at least one steroid-sparing systemic treatment commonly found to be useful in patients with dermatomyositis. These may include azathioprine, cyclosporine, mycophenolate mofetil, IVIG, methotrexate, cyclophosphamide, chlorambucil, sirolimus, adalimumab, infliximab and rituximab.
• Use of topical medications and sunscreen currently and in past will be noted but not weighed for assessment of refractory cutaneous disease

Exclusion criteria:

• Patients with dermatomyositis who have minimal-to-no active cutaneous features (focal involvement with less than 1% total body surface area involved or minimal modified CDASI activity score)
• Patients whose cutaneous findings are not consistent with dermatomyositis and/or have previous biopsy results suggestive of an alternative diagnosis
• Patients with inflammatory myositis other than dermatomyositis, such as polymyositis or inclusion body myositis
• Patients with malignancy-associated dermatomyositis
• Patients with clear features of an overlap myositis
• Patients younger than 18 years old
• Patients with acutely active or chronic infections
• Patients with uncontrolled diabetes, hypertension, cardiovascular, hepatic or renal disease
• Pregnant or lactating females
• Patients with any medical condition that is felt by the primary investigator to place the patient at unreasonable risk for adverse effects during treatment with H.P. Acthar
• Hypersensitivity to H.P. Acthar, any of its components (allergy to pig-derived proteins)
• Patients with osteoporosis
• Patients who have had surgery within 8 weeks of screening
• Patients with a history of or current gastric ulcers
• Patients taking daily doses of systemic corticosteroids greater than the equivalent of 40mg prednisone

NCT03813160: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial to Evaluate Efficacy and Safety of Lenabasum in Dermatomyositis. This phase three trial is of an oral medication that is a cannabinoid receptor agonist, from a company named Corbus.

Inclusion criteria:

• Fulfill one of the following criteria for dermatomyositis:
  1. Bohan and Peter criteria (Bohan and Peter, 1975a; Bohan and Peter 1975b)
  2. ACR/EULAR criteria (Lundberg et al, 2017)
• Disease activity/severity fulfills one of the following three criteria:
  1. MDGA ≥ 3 cm (0 – 10 cm Visual Analog Scale [VAS]) and MMT-8 score ≤ 142 (out of 150 total possible)
  2. Sum of MDGA, PtGA and EMGA VAS scores is ≥ 10 cm (0-10 cm VAS for each)
  3. MDGA ≥ 3 cm (0-10 cm VAS) and CDASI activity score of > 14
• Stable doses of immunosuppressive medications for DM as defined by:
  1. Unchanged dose of oral corticosteroids ≤ 20 mg per day prednisone or equivalent for ≥ 4 weeks before Visit 1
  2. Unchanged dose of immunosuppressive medications other than oral corticosteroids for ≥ 8 weeks before Screening

Exclusion criteria:

• Unstable DM or DM with end-stage organ involvement at Screening or Visit 1
• Significant diseases or conditions other than DM that may influence response to the study drug or safety
• Any of the following values for laboratory tests at Screening:
  1. A positive pregnancy test (or at Visit 1)
  2. Hemoglobin < 9 g/dL in males and < 8 g/dL in females
  3. Neutrophils < 1.0 × 10^9/L
  4. Platelets < 75 × 10^9/L
  5. Creatinine clearance < 50 mL/min on screening blood test, per the Modification of Diet in Renal Disease Study or in 24 hour urine creatine clearance measurement

Dr. Fernandez is Director of Medical Dermatology.