What are the alternatives or generics to Dupixent (dupilumab)?

Alternatives to Dupixent (Dupilumab)

For moderate-to-severe atopic dermatitis, tralokinumab is the first-line alternative to dupilumab, followed by JAK inhibitors (upadacitinib or abrocitinib) as second-line alternatives. 1

No Generic Available

• Dupilumab is a biologic medication (monoclonal antibody) with no generic equivalent currently available 2
• As a complex biologic, generic versions (biosimilars) are not yet on the market

First-Line Alternative: Tralokinumab

Tralokinumab should be your first choice when switching from dupilumab. 1

• Targets IL-13 specifically (unlike dupilumab which blocks both IL-4 and IL-13) 1
• Similar efficacy profile to dupilumab with potentially fewer side effects 1
• Particularly valuable for patients with dupilumab-associated arthralgia—all 15 patients in a recent case series achieved resolution of joint pain after switching to tralokinumab while maintaining clear or nearly clear skin 3
• Preferred option for females planning pregnancy over JAK inhibitors 1

Second-Line Alternatives: JAK Inhibitors

Upadacitinib

• Oral selective JAK-1 inhibitor dosed at 15mg or 30mg daily 1
• Superior efficacy to dupilumab in head-to-head trials—71.0% achieved EASI-75 at week 16 vs 61.1% with dupilumab (p=0.006) 4
• More rapid onset: 43.7% achieved EASI-75 by week 2 vs 17.4% with dupilumab 4
• Higher rate of complete clearance (EASI-100): 27.9% vs 7.6% with dupilumab 4

Abrocitinib

• Oral selective JAK-1 inhibitor dosed at 100mg or 200mg daily 1
• Demonstrated superior efficacy to dupilumab in head-to-head trials 1
• May resolve dupilumab-related ocular surface disorders (DROSD)—limited data shows 2 of 3 patients had resolution of eye symptoms by 12 weeks after switching 5

Critical Safety Warnings for JAK Inhibitors

The FDA warns of increased risk of serious cardiovascular events, cancer, blood clots, and death with JAK inhibitors. 1

• Requires baseline laboratory testing and regular monitoring 1
• Higher rates of serious infection, eczema herpeticum, and herpes zoster compared to dupilumab 4
• These risks must be weighed against the superior efficacy profile

Other Treatment Options

Phototherapy

• Conditionally recommended for adults with atopic dermatitis (low certainty evidence) 1
• Consider when biologics or JAK inhibitors are not appropriate

Baricitinib

• JAK-1 and JAK-2 inhibitor approved in Europe but not FDA-approved for atopic dermatitis in the US 1
• Less efficacy than upadacitinib and abrocitinib based on network meta-analysis 1

When to Switch from Dupilumab

Ocular Complications

Switch if any of the following occur: 5

• Progressive conjunctival scarring not responding to treatment that risks visual acuity loss
• Requirement for prolonged topical corticosteroids (>8 weeks) with risk of serious ocular adverse effects
• Significant quality of life loss from inadequately controlled eye symptoms

Musculoskeletal Side Effects

• Dupilumab-associated arthralgia, arthritis, or enthesitis warrant switching to tralokinumab 3
• IL-4 inhibition may promote Th17-dominant immune response contributing to joint symptoms 3

Inadequate Response

• Partial responders or non-durable responders should first maximize topical therapy and rule out alternative diagnoses before switching 6
• Consider combination with traditional immunosuppressants before abandoning dupilumab entirely 6

Monitoring Requirements

• JAK inhibitors: Baseline labs and regular monitoring required 1
• Tralokinumab: Similar monitoring to dupilumab with assessment for treatment efficacy and adverse effects 1
• Regular follow-up for all alternatives to assess disease control 1