DUPILUMAB INJ,SOLN
Clinical Criteria Summary
Document 55
Exclusion Criteria
- Concurrent use of live (attenuated) vaccines or treatment with live (attenuated) vaccines within the previous 4 weeks.
- Concurrent use with targeted immunomodulators unless potential risk-benefits favor use.
- Untreated parasitic (helminth) infection.
- Existing diagnosis of cutaneous T-cell lymphoma (CTCL), mycosis fungoides, or Sézary syndrome unless potential benefits outweigh risks (relative contraindication).
Inclusion Criteria (New Starts)
- Diagnosis of chronic atopic dermatitis made or confirmed by a VA / VA Community Care dermatologist.
- Prescribed by a VA / VA Community Care dermatologist, allergist, or immunologist, or other designated expert in the management of atopic dermatitis in consultation with a VA / VA Community Care dermatologist, allergist, or immunologist.
- Offered all age-appropriate vaccinations prior to initiating therapy.
- Assessment of moderate to severe atopic dermatitis in the last 2 weeks as determined by either a gestalt assessment of “moderate” or “severe” OR Eczema Area and Severity Index (EASI) ≥ 16 (scale 0–72).
- Refractory to ≥ 2 classes of topical therapies for atopic dermatitis (e.g., corticosteroids, calcineurin inhibitors, PDE4 inhibitors, JAK inhibitors) for ≥ 4 weeks total unless the therapy is medically inadvisable or not tolerated.
Additional Inclusion Criteria
- For females who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy.
- For females who are breastfeeding/providing breastmilk to an infant: Counseling provided on potential risks vs benefits of treatment.
Sequencing & Therapy Considerations
- If patient weighs < 100 kg, consider tralokinumab prior to dupilumab.
- First-line therapies include dupilumab, tralokinumab-ldrm, lebrikizumab-lbkz, or nemolizumab-ilto.
- Second-line therapies include abrocitinib or upadacitinib.
- Consider offering methotrexate, azathioprine, mycophenolate mofetil in the context of shared decision-making (prior trials not required), with use conditional on factors such as lower certainty of risk-benefits, slower onset, feasibility of adhering to follow-ups, comorbidities, and patient values/preferences.
Document 216
Exclusion Criteria
- History of hypersensitivity to dupilumab or any of its excipients
- Concurrent use of live (attenuated) vaccines or treatment with live (attenuated) vaccines within the previous 12 weeks
- Currently treated with omalizumab or another biologic agent
- Untreated parasitic (helminth) infection
Inclusion Criteria
- Care provided by a VA / VA Community Care (Allergy, Immunology or Otolaryngology [ear, nose and throat] specialist) or locally designated expert in managing CRSwNP
- Diagnosis of CRSwNP is confirmed
- Symptoms of CRSwNP are uncontrolled and persistent despite use of ALL of the following:
- Daily use and adherence to topical corticosteroid (CS) nasal spray (e.g., fluticasone)
- Daily use and adherence to nasal saline spray/irrigations
- Trial of nasal CS irrigation (e.g., 4-6 weeks budesonide added to topical CS and nasal saline sprays/irrigations)
- Short-term course of systemic CS within the past 2 years (unless contraindicated)
- Sinonasal surgery has been performed (e.g., surgical/endoscopic intervention(s) to remove nasal polyps/tissue, unless patient is not a surgical candidate or surgery is not indicated) and continued adherence to maximal medical therapies after surgery has been confirmed with the patient
Dosing & Administration
- FDA-approved dosing schedule for CRSwNP is every 2 weeks
- Clinical trials (SINUS-24 and SINUS-52) showed no statistically different outcomes between administering dupilumab every 2 weeks vs. every 4 weeks
Safety & Clinical Management
- Hypersensitivity reactions reported in <1% of patients in clinical trials (e.g., generalized urticaria, rash, erythema nodosum and serum sickness or serum sickness-like events)
- If a hypersensitivity reaction occurs, appropriate therapy should be instituted and dupilumab discontinued
Document 377
Exclusion Criteria
- Concurrent use of live (attenuated) vaccines or treatment with live (attenuated) vaccines within the previous 12 weeks
- Untreated parasitic (helminth) infection
Inclusion Criteria
- Diagnosis of eosinophilic esophagitis (EoE) including histologic evidence of eosinophilic inflammation (≥ 15 eosinophils / high power field) made or confirmed by a VA / VA Community Care gastroenterologist
- Prescribed by a VA / VA Community Care gastroenterologist OR an immunologist, allergist, or other designated expert in the management of EoE in consultation with a VA / VA Community Care gastroenterologist
- Tried a swallowed topical glucocorticoid (e.g., swallowed aerosolized fluticasone or commercially available budesonide oral suspension) for at least 8 to 12 weeks, unless medically inadvisable, and had an inadequate response or intolerance
Additional Inclusion Criteria
- For patients who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy
Document 378
Indication
- Treatment of adults with eosinophilic esophagitis (EoE)
Patient Selection & Clinical Criteria
- Histologic confirmation of eosinophilic inflammation (≥ 15 intraepithelial eosinophils per high-power field [eos/hpf])
- Significant symptoms: average ≥ 2 episodes of dysphagia with intake of solids per week in the previous 4 weeks
- Inadequate response or intolerance to prior trials of proton pump inhibitors (PPIs) administered twice daily for ≥ 8 weeks
- Prior trials of swallowed topical glucocorticoids (STGs) (≥ 8 weeks) and dietary therapy are considered, though a prior trial of systemic glucocorticoids is not required
- Patients should be strongly motivated/adherent with access to dietitian support if dietary therapy is utilized
Dosing & Administration
- 300 mg subcutaneous (SC) every week (QW)
- Dose is higher and more frequent than for other approved indications
Place in Therapy
- Third-line pharmacologic treatment alternative for EoE
Safety Considerations & Monitoring
- Adverse events observed include injection site reactions, upper respiratory tract infections, arthralgia, and herpes viral infections (≥ 2% incidence)
- Conjunctivitis and keratitis were reported at 0% in the dupilumab group
- Long-term safety and risk of loss of efficacy require further assessment beyond short-term trials
- Symptomatic remission does not reliably correlate with histologic remission; both histologic end points (reduction in eosinophilic inflammation) and clinical signs/symptoms are important outcome measures
Un-Evaluated Populations & Precautions
- Safety and efficacy have not been evaluated in patients in complete symptomatic remission
- Safety and efficacy have not been evaluated in patients with prior esophageal surgery
- Safety and efficacy have not been evaluated in patients with an esophageal stricture unable to be passed with a 9- to 10-mm standard diagnostic endoscope
- Safety and efficacy have not been evaluated in patients with a critical esophageal stricture requiring dilation
- Use in the above un-evaluated populations should be adjudicated on a case-by-case basis
Document 517
Indication & Patient Population
- • Treatment of adult patients with prurigo nodularis (PN)
- • Patients with a documented diagnosis of PN and ≥ 20 nodules
- • Patients presenting with severe itch despite use of topical therapies
Treatment Prerequisites & Step Therapy Requirements
- • Inadequate response (after ≥ 2 weeks per therapy) or intolerance to one of the following:
- – Two topical therapies (e.g., medium, high, or super-high corticosteroids [where different strengths count as different therapies], calcipotriene, or calcineurin inhibitor)
- – One topical therapy and an intralesional corticosteroid
- • Applicable unless these prior therapies are medically inadvisable
Dosing & Administration
- • Initial: 600 mg (two 300-mg injections) subcutaneously (SC)
- • Maintenance: 300 mg SC every 2 weeks
- • Formulation: Single-dose prefilled syringe or single-dose prefilled pen: 300 mg/2 mL
Safety & Clinical Considerations
- • Boxed warnings, contraindications, and other warnings/precautions apply as for previous indications
- • Common adverse events (≥ 2% of dupilumab group and greater than placebo): Nasopharyngitis, conjunctivitis, herpes infection, dizziness, myalgia, diarrhea
- • Patients with atopic dermatitis-related PN require more weeks of treatment to achieve response compared to non-atopic dermatitis-related PN patients
- • Complete remission is rarely observed before 4 months of therapy; 2 months of therapy are required before itch is relieved
Document 707
Provider & Care Setting
- Provider must be a VA or VA Community Care pulmonologist or designated expert.
Disease Severity & Phenotype
- Moderate to severe COPD (post-bronchodilator FEV 30-70% predicted and FEV /FVC <0.7, confirmed by pulmonary function testing).
- Signs or symptoms of chronic bronchitis (chronic productive cough) for at least 3 months during the past year.
Exacerbation History & Symptom Control
- At least 2 moderate COPD exacerbations (requiring systemic steroids and/or antibiotics) or at least 1 severe COPD exacerbation (requiring hospitalization) in the previous 12 months.
- Inadequate symptom control (e.g., mMRC dyspnea scale score > 2.) or impaired health status (e.g., CAT score > 15).
Biomarkers
- Blood eosinophils ≥300 cells/µL obtained prior to treatment (e.g., within the prior 3 months).
Prior Therapy & Treatment Trials
- Receiving concurrent triple inhaled therapy with a long-acting beta-agonist (LABA) AND a long-acting anticholinergic (LAMA) AND an inhaled corticosteroid (unless inhaled corticosteroid is contraindicated) for at least 3 months.
- Unable to tolerate or had an inadequate response to a (6-month) trial of roflumilast and to a (6-month) trial of azithromycin, unless not clinically appropriate for either agent.
Adherence & Technique
- Adherent to COPD medications as evidenced by a review of prescription refill history.
- Demonstrated correct inhaler technique (documented in chart).
Safety & Contraindications (Exclusion Criteria)
- Untreated acute bronchospasm or an acute exacerbation of chronic obstructive pulmonary disease (COPD).
- Concurrent use of live (attenuated) vaccines or treatment with live (attenuated) vaccines within the previous 4 weeks.
- Untreated parasitic (helminth) infection (treat infection prior to initiating dupilumab).
- Concurrent use with therapeutic biologics unless potential benefit-risk favors use.
Special Populations & Additional Considerations
- For patients who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy.
- Patient is non-smoking or, if not, enrolled in a quit smoking program or on medications to assist with smoking cessation (current smokers may be considered if unable or refuse to quit).
- Address modifiable environmental triggers for Type 2 inflammation, if not already done.
Document 800
Indication & Patient Population
- Adults with bullous pemphigoid (BP)
- Moderate to severe BP or patients requiring systemic therapy
- Refractory/resistant to combined topical corticosteroids (TCS) and oral corticosteroids (OCS)
- Histopathologically, immunopathologically, and serologically confirmed diagnosis
- Bullous Pemphigoid Disease Area Index (BPDAI) activity score ≥ 24
- Weekly average Peak Pruritus NRS (PP-NRS) score ≥ 4
Dosing & Administration
- 600 mg SC once, then 300 mg SC every 2 weeks
- Use in combination with a tapering course of OCS
- Once disease control occurs, gradually taper OCS and continue dupilumab as monotherapy
- Add corticosteroids if medically advisable in case of relapse
Pretreatment & Monitoring
- No pretreatment procedures required
- No laboratory monitoring required
- Monitor for keratoconjunctivitis
Safety Considerations
- Nonimmunosuppressant (advantageous for older patients with comorbidities)
- Top 5 adverse events: arthralgia, conjunctivitis, blurred vision, herpes viral infections, keratitis
Place in Therapy
- FDA-approved for BP
- Potential first-line (1L) treatment in combination with a tapering course of OCS for moderate to severe BP or when systemic therapy is indicated
- Considered for BP resistant to combined TCS and OCS; once disease controlled, OCS may be tapered before continuing dupilumab as monotherapy
Document 801
Indication & Patient Population
- Adults and pediatric patients > 12 years with chronic spontaneous urticaria (CSU)
- Patients who remain symptomatic despite treatment with H1 antihistamines (up to 4x usual daily dose)
- Not indicated for patients with inducible urticaria, diseases other than urticaria associated with hives or angioedema, active atopic dermatitis, or other skin conditions that could interfere with outcome assessments
Dosing & Administration
- Initial dose: 600 mg
- Maintenance dose: 300 mg every 2 weeks
- Continue H1 antihistamines; titrate up to 4x usual daily dose as needed
- Rescue therapy with oral corticosteroids is permitted
Safety, Monitoring & Precautions
- Contraindicated in patients with known hypersensitivity to dupilumab or any excipients
- Monitor for and report: Hypersensitivity; conjunctivitis and keratitis (report new eye symptoms); eosinophilic conditions (especially upon reducing oral corticosteroid dose); psoriasis (new onset); arthralgia and psoriatic arthritis (report new onset joint symptoms)
- Steroid withdrawal precautions: Do not abruptly discontinue oral, topical, or inhaled corticosteroids upon initiation; if needed, gradually decrease steroids
- Parasitic (Helminth) infections: Treat preexisting infections before initiating treatment
- Vaccines: Avoid use of live vaccines
- Pregnancy: Monitor via pregnancy registry; case reports and series have not identified a dupilumab-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes
- Lactation: Weigh benefits of breastfeeding against mother’s clinical need and potential adverse drug events on the breastfed child
Place in Therapy & Step-Down Criteria
- Recommended as a second-line therapy for patients remaining symptomatic on H1 antihistamines (up to 4x daily dose)
- Maximum doses of H1 antihistamines should be continued in combination with second-line therapies
- Not recommended for patients who have not had an adequate response to omalizumab, as they are unlikely to show a greater response to dupilumab
- Therapy can be stepped down by reducing doses or extending dosing intervals when the urticaria control test (UCT) score equals 16
Document 815
Exclusion Criteria
- Concurrent use of live (attenuated) vaccines or treatment with live (attenuated) vaccines within the previous 4 weeks
- Concurrent use with therapeutic biologics unless potential risk-benefits favor use
- Untreated parasitic (helminth) infection
Inclusion Criteria (Prerequisites)
- Prescribed by a VA / VA Community Care dermatologist or other designated expert in the management of bullous pemphigoid in consultation with a VA / VA Community Care dermatologist
- Medications potentially implicated as causing bullous pemphigoid have been discontinued or switched if clinically possible (but this should not necessarily delay initiation of therapy)
Inclusion Criteria (Disease Severity & Treatment History)
- One of the following must be selected:
- Documented biopsy and/or serology-confirmed, moderate–severe bullous pemphigoid with moderate–very severe pruritus AND concomitant tapering course of oral corticosteroids unless medically inadvisable
- Documented mild bullous pemphigoid AND had an inadequate response (after ≥ 4 weeks), intolerance, or medical inadvisability to either high potency topical corticosteroids or oral corticosteroids and either doxycycline/tetracycline or dapsone
Additional Inclusion Criteria (Special Populations)
- Select if applicable:
- For females who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy
- For females who are lactating/providing breastmilk to an infant: Counseling provided on the potential risks vs benefits of treatment
Document 816
Exclusion Criteria
- Concurrent use of live or live attenuated vaccines (within the past 4 weeks)
- Untreated parasitic (helminth) infection (treat infection prior to initiating dupilumab)
- Concurrent use with therapeutic biologics unless potential benefit-risk favors use
Inclusion Criteria
- Provider is a VA or VA Community Care allergy specialist, dermatologist or designated expert in the management of allergic conditions
- Diagnosis of severe chronic spontaneous urticaria (e.g., UAS7 >28 and/or UCT <12)
- Unacceptable symptoms despite a therapeutic trial of 1 non-sedating H antihistamine titrated up to 4 times the usual daily dose
- Inadequate response to a 3-month trial of omalizumab 300 mg every 4 weeks (minimum of 3 doses), unable to tolerate or not a candidate for omalizumab
Additional Inclusion Criteria
- For patients who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy; if pregnancy occurs, enrollment in a pregnancy register is recommended