ProDERM Study Design: IVIg Therapy for Adults With DM

The First and Only IVIg Therapy With a Successful Phase 3 Study Resulting in FDA Approval for Dermatomyositis in Adults1-3

ProDERM is a multicenter, prospective, double blind, randomized clinical trial to evaluate the long-term efficacy, tolerability & safety of IVIg in a large multinational population of adults with DM.

  • Enrolled 95 adult patients from 36 sites in 10 countries (17 sites in the US)
    • Included patients who were receiving standard immunosuppression (corticosteroids and/or immunosuppressants) or who previously failed or were intolerant to standard immunosuppression
    • Study design allowed patients to switch treatment if they deteriorated
  • 47 subjects received octagam 10% and 48 subjects received placebo in an initial 16‑week, double-blinded First Period, followed by a 6-month, open-label Extension Period, during which all subjects who were eligible to continue received octagam 10% every 4 weeks. Forty-five subjects in the initial octagam group and 46 subjects in the placebo group entered the Extension Period
  • Enabled recruitment of a large number of patients for such a rare disease
    • Large patient population helps make results applicable in clinic practice, given the heterogenous nature of DM

CD=confirmed deterioration.

Patient Demographics1-3

Inclusion Criteria

Patients who met the following criteria were eligible for the study:

  • Males or females ≥18 to <80 years of age
  • Diagnosis of definite or probable DM according to the Bohan and Peter criteria
  • Patients under treatment with:
    • Corticosteroids and/or maximally 2 immunosuppressants and being on stable therapy for at least 4 weeks
      OR
    • Previous failure of response or previous intolerance to corticosteroid and at least 1 additional immunosuppressive drug, and with steroid/immunosuppressive drugs washed out
  • Patients with active disease, assessed and agreed upon by the Independent Adjudication Committee (IAC)
  • Manual Muscle Testing-8 (MMT-8) score <142, with at least 2 other abnormal core set measures (Visual Analogue Scale [VAS] of patient global activity ≥2 cm, physician’s global disease activity (GDA) ≥2 cm, extra-muscular activity ≥2 cm; at least one muscle enzyme >1.5 times upper limit of normal, Health Assessment Questionnaire [HAQ] ≥0.25)

Patients were Typical of a DM Population Encountered in Clinical Practice

Demographic characteristics were balanced across octagam 10% and placebo.

  • Patient age ranged from 22 to 79 years, with a mean age of around 53 years
  • Approximately 90% of patients were Caucasian
  • Overall, the majority of patients were female: around 75% vs 25% males
  • Approximately 70% of patients were enrolled at sites outside of the US
  • The median time since diagnosis of DM was similar in both treatment groups: 2.35 years in the octagam 10% group; 2.86 years in the placebo group
  • The majority of patients (70.5% overall) were classed as having definite DM, the other 29.5% as having probable DM
  • Mean time since diagnosis of DM was around 4.5 years (octagam 10% 5.3 years, placebo 3.9 years)
  • All patients (100%) had muscle weakness and typical DM rash, and more than 90% of patients had elevated muscle enzymes
ProDERM Patient Demographics
Parameter N (%)octagam 10% (n=47)Placebo (n=48)Total (N=95)
Median Age55 years51.5 years52 years
Female36 (76.6%)35 (72.9%71 (74.7%)
Male11 (23.4%)13 (27.1%)24 (25.3%)
Median Time Since DM Diagnosis2.35 years2.86 years2.57 years
Bohan and Peters Criteria
Proximal muscle weakness47 (100%)48 (100%)95 (100%)
Muscle biopsy evidence of myositis23 (48.9%)23 (47.9%)46 (48.4%)
Elevation of muscle enzymes43 (91.5%)44 (91.7%)87 (91.6%)
EMG evidence of myositis31 (66%)26 (54.2%)57 (60%)
Typical DM skin rash47 (100%)48 (100%)95 (100%)
Classification of DM
Definite34 (72.3%)33 (68.8%)67 (70.5%)
Probable13 (27.7%)15 (31.3%)28 (29.5%)
Physician Global Disease Activity
Mild11 (23.4%)15 (31.3%)26 (27.4%)
Moderate29 (61.7%)27 (56.3%)56 (58.9%)
Severe7 (14.9%)6 (12.5%)13 (13.7%)
Premedication for Infusion
Any10 (21.3%)4 (8.3%)14 (14.7%)
Analgesics5 (10.6%)1 (2.1%)6 (6.3%)
Antihistamines4 (8.5%)2 (4.2%)6 (6.3%)

EMG=electromyogram.

Concomitant Medication Use

  • 98.9% of patients continued on their stable prior DM medications
  • A similar proportion of patients used concomitant DM medications in both treatment arms. The most common were: systemic corticosteroids (88%); immunosuppressants (57%); and anti-inflammatory and anti-rheumatic products (21%)

Study Endpoints1-3

PRIMARY ENDPOINT: Efficacy was based on proportion of patients responding to treatment at Week 16, defined as improvement of ≥20 points on Total Improvement Score (TIS). TIS is measured on a scale of 0 to 100 (20=minimal; 40=moderate; 60=major), and is based on 6 core set measures:

  1. Physician global disease activity (GDA).  Part of Myositis Disease Activity Assessment Tool (MDAAT) assessed by Investigator on Visual Analog Scale (VAS)
  2. Manual muscle testing MMT-8. Evaluation of strength in a muscle or muscle group based on performance of a movement
  3. Muscle enzymes, Aldolase, creatine kinase, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase)
  4. Patient global disease activity (GDA). Assessed by the patient on a VAS
  5. Health Assessment Questionnaire (HAQ). Assessed by the patient
  6. Extramuscular disease activity. Part of MDAAT assessed by investigator on VAS

SECONDARY ENDPOINTS:

  • Proportion of TIS responders with at least moderate or major improvement
  • TIS responders at 40 weeks
  • Mean TIS at the end of placebo-controlled period (4 months) and at the end of the open-label extension period (10 months)
  • Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI)
    • Mean change at 4 months and 10 months
    • Assesses erythema, scale, and erosion/ulcerations over 15 areas, including:
      scalp, face, neck, upper back and shoulders, buttocks, arms, abdomen, hands, thigh, legs and feet
    • Total scale of 0-100 (lower scores indicate lower disease severity)
  • Safety and tolerability

Review octagam 10% clinical efficacy in adult patients with DM.

References:
  1. Octagam 10% Full Prescribing Information. Paramus, NJ: Octapharma USA Inc; rev June 2021.
  2. Octapharma. Data on file.
  3. Aggarwal R, et al. (ProDERM study). Submitted for publication. August 2021.