Nemolizumab Therapeutic Cheat Sheet

Atopic dermatitis and prurigo nodularis are chronic, life-altering diseases with a common feature of debilitating pruritus that significantly impacts our patients’ qualities of life. For those with resistant and extensive disease, dermatologists now have nemolizumab in our armamentarium, the first FDA approved IL-31 inhibitor. We continue our series, Therapeutic Cheat Sheet, with a closer look at nemolizumab, which is FDA-approved for the treatment of moderate-to-severe atopic dermatitis and prurigo nodularis.

Nemolizumab Therapeutic Cheat Sheet

Compiled by: Dillon Nussbaum, MD | Reviewed by: Adam Friedman, MD

TRADE NAME

• • Nemluvio

MECHANISM OF ACTION^12-17

• • Interleukin-31 antagonist: binds IL-31 cytokine, preventing interaction with its receptor, IL-31RA, and therefore, all biological activity of this cytokine
    • Pruritus in atopic dermatitis and prurigo nodularis is largely driven by type-2 immunity, including what is being called the itch cytokine, IL-31
    • The concentration of IL-31 is significantly increased in lesional skin compared to controls in patients with atopic dermatitis and prurigo nodules

FDA APPROVED FOR^14-15

• • Moderate-to-severe atopic dermatitis
  • Prurigo Nodularis

OFF-LABEL DERMATOLOGIC USES^6,11,12

• • Generalized pruritus
  • Uremic pruritus
  • Lichen simplex chronicus
  • Macular/Lichen Amyloidosis

DOSING (SUBCUTANEOUS INJECTION)^12-17

• • Prurigo nodularis dosing:
    • Adult patients weighing less than 90kg:
      • Initial dose of 60 mg (two 30 mg injections) followed by 30 mg (one 30 mg injection) every four weeks
    • Adult patients weighing more than 90kg:
      • Initial dose of 60 mg (two 30 mg injections) followed by 60 mg (two 30 mg injections) every four weeks
    • Atopic dermatitis dosing:
      • For adults and adolescents aged 12 years and older:
        • Initial dose of 60 mg (two 30 mg injections) followed by 30 mg (one 30 mg injection) every four weeks

ADMINISTRATION^12-17

• • Patients should be brought up to date with all vaccinations prior to initiating therapy with nemolizumab
  • Nemolizumab must be reconstituted prior to administration:
    1. Remove from refrigerator and allow to reach room temperature (30-45 minutes), nemolizumab is safe at room temperature for 90 days unless reconstituted, if so, it must be used within four hours
    2. Inspect dual chamber, do not use if powder is not white or dilutant is cloudy or has visible particles
    3. Turn the activation knob at the bottom to the right until it stops (towards the unlock icon), this will start the reconstitution
    4. Shake the pen up and down for thirty seconds, wait five minutes for bubbles to decrease and powder dissolved, consider shaking again for thirty seconds and wait another five minutes for bubbles to decrease if needed
    5. Twist the gray cap, do not pull, until the orange needle guard pops up and remove gently
    6. Place pen perpendicular to injection site, anterior thigh or abdomen, deltoid only if by caregiver, apply pressure until the orange needle guard is pushed inward, a click should be heard, hold for 15 seconds, lift the pen up vertically and place in sharps container, cotton ball or gauze for injection site bleeding

SIDE EFFECTS^8,9,10

• • Neurological: Headache
  • Cutaneous: Hypersensitivity reactions (angioedema), new onset or exacerbated atopic dermatitis, eczema, nummular dermatitis, bullous pemphigoid, asthma
  • Respiratory: nasopharyngitis, upper respiratory tract infection
  • Musculoskeletal: elevated creatine kinase and peripheral edema

DRUG INTERACTIONS^14,15

• • Nemolizumab may decrease serum concentration of cytochrome P450 (CYP450) substrates: upon initiation or discontinuation of nemolizumab, consider monitoring for effect or drug concentration and consider dosage modification (e.g., warfarin, cyclosporine, etc.)
  • Nemolizumab may diminish the therapeutic effect of Fc receptor binding agents such as efgartigimod alfa and rozanolixizumab

CONTRAINDICATIONS^12,14,15

• • Known hypersensitivity to nemolizumab or to any of the excipients in nemolizumab
  • Avoid use of live vaccines

PREGNANCY AND BREASTFEEDING^12,14,15

• • Available data on nemolizumab use in pregnant women exposed in clinical trials are insufficient to evaluate for drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes
  • Transport of IgG antibodies across the placenta increase during pregnancy, therefore nemolizumab may be transferred to a developing fetus
  • There is no data on the presence of nemolizumab in human milk, the effects on the breastfed infant, or effects on milk production, nemolizumab has been noted in the milk of monkeys after exposure

MONITORING^12,14,15

• • No lab monitoring required

INSURANCE COVERAGE (all criteria must be met)^1-5,7,18,19

• • Atopic Dermatitis:
    • Diagnosis of moderate-to-severe AD
    • Prescribed by or in consultation with a specialist, such as a dermatologist, allergist, or immunologist
    • At least 10% body surface area involvement
    • History of failure, contraindication, or intolerance to previous AD treatment(s), such as topical corticosteroids, topical calcineurin inhibitors, or a topical PDE4 inhibitor
    • Patient is not receiving nemolizumab in combination with another biologic immunomodulator or JAK inhibitor
  • Prurigo Nodularis:
    • Diagnosis of prurigo nodularis (PN)
    • Prescribed by or in consultation with a specialist, such as a dermatologist, allergist, or immunologist
    • 20 or more PN lesions
    • Pruritus duration for ≥6 weeks
    • History of failure, contraindication, or intolerance to previous PN treatment(s), such as phototherapy, topical corticosteroids, topical calcineurin inhibitors, methotrexate, or cyclosporine
    • Patient is not receiving nemolizumab in combination with another biologic immunomodulator

FURTHER READING

If you would like to learn more about nemolizumab, check out the following articles published in the Journal of Drugs in Dermatology:

Selection of Nemolizumab Clinical Dosage for Atopic Dermatitis

Wagner, L. Loprete, V. Duval, P. Jauslin, K. Benkali, J.I. Silverberg, A. Wollenberg, T. Saito, F. Ahmad, M. Graeber, W. Winkelman, and C. Piketty

Abstract:

Nemolizumab is a monoclonal antibody directed against the interleukin-31 receptor A subunit, which is involved in the pathogenesis of pruritus and inflammation in atopic dermatitis (AD). Clinical trial results were combined with population PK (popPK) and pharmacokinetic/ pharmacodynamic (PK/PD) models to optimize nemolizumab dosing. Phase 1 and 2a clinical studies indicated that weight-based nemolizumab dosing reduced pruritus in patients with moderate-to-severe AD with good safety and tolerability even at the highest dose (3 mg/kg single dose and 2 mg/kg multiple doses). Nemolizumab PK profile was characterized by a slow absorption with peak serum concentrations reached 4.5-9.2 days post-dose, and a long terminal half-life ranging from 12.6 to 16.5 days. A change from weight-based dosing to flat dose was supported by an additional phase 2b study sponsored by Galderma. Flat dosing provides several practical advantages, including ease of preparation for self- or auto-injection and reduced chance of dosing errors. Doses of 10, 30, and 90 mg were selected based on popPK and PK/PD simulations to result in nemolizumab serum concentrations sufficient to achieve efficacy. Loading doses were administrated at the 2 lower doses in order to achieve target systemic concentrations from the first injection. The efficacy of Nemolizumab in improving cutaneous signs of inflammation and pruritus in AD and its safety profile, combined with popPK and PK/PD analyses, supported selection of the flat-dose regimen of 30 mg (with a 60 mg loading dose) given every 4 weeks subcutaneously for 16 weeks in the phase 3 ARCADIA studies sponsored by Galderma.

J Drugs Dermatol. 2023;22(10):1017-1020.

Patient Journey and the Burden of Systemic Comorbidities and Sequalae in Prurigo Nodularis

S.G. Kwatra, S.S. Chisolm, K.S. Puerta Durango, and N.K. Mollanazar

Abstract:

Prurigo Nodularis (PN) is a relatively rare chronic inflammatory skin disease characterized by firm pruritic nodules. PN is associated with significantly increased rates of many systemic and non-systemic comorbidities. This results in a higher burden of disease and utilization of specialty care compared to non-PN United States (US) adults. Psychiatric comorbidities associated with PN include depression and anxiety. In this article, we describe the burden of comorbidities. sequelae of disease, inflammatory disease signatures, and the impact of PN in African American and Asian patients. Furthermore, we explore challenges in the recognition and diagnosis of PN and describe methods to increase awareness of PN among dermatologists.

J Drugs Dermatol. 2023;22(12):12-14.

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