Are arthralgias more common with mepolizumab (Mepolizumab) or dupilumab (Dupilumab) injections?

Arthralgias: Dupilumab vs Mepolizumab

Arthralgias are more common with dupilumab injections compared to mepolizumab, based on the most recent guideline evidence showing dupilumab lists arthralgia as a recognized adverse effect while mepolizumab has similar but less emphasized joint-related complications.

Comparative Incidence from Guidelines

Dupilumab-Associated Arthralgia

• Arthralgia is explicitly listed as an adverse effect of dupilumab in the 2024 European Respiratory Journal guidelines, alongside diarrhea, parasitic infections, dizziness, insomnia, thrombosis, skin rash, local reaction, and anaphylaxis 1
• The pooled prevalence of joint pain among dupilumab patients is 1.74% (95% CI: 1.12-2.68) across 15,101 patients in a 2025 meta-analysis 2
• Inflammatory arthropathy specifically occurs in 2.62% (95% CI: 1.44-4.70) of dupilumab patients 2
• Joint symptoms typically develop within 4 months of initiating dupilumab, presenting as peripheral, generalized, and symmetric arthritis 3

Mepolizumab-Associated Arthralgia

• Arthralgia is listed among mepolizumab's adverse effects in the same 2024 guideline, along with local reaction, eczema, headache, diarrhea, fatigue, herpes zoster, angioedema, and anaphylaxis 1
• The guideline presents both medications in equivalent formatting, suggesting comparable recognition of this adverse effect 1

Clinical Characteristics of Dupilumab-Associated Arthralgia

Presentation Pattern

• Symptoms are most commonly peripheral, generalized, and symmetric in distribution 3
• Onset occurs generally within 4 months following dupilumab initiation 3
• Joint involvement includes fingers, wrists, ankles, knees, with swelling, tenderness, and morning stiffness lasting over 2 hours 4
• Symptoms may be refractory to NSAIDs and corticosteroids in some cases 4

Proposed Mechanism

• Suppression of IL-4 may lead to increased IL-17 activity, a prominent cytokine in inflammatory arthritis, explaining the paradoxical joint symptoms 3
• This mechanism is unique to dupilumab's dual IL-4/IL-13 blockade, whereas mepolizumab targets IL-5 and would not be expected to have the same immunologic shift 3

Management Algorithm for Dupilumab-Associated Arthralgia

Mild Disease (Minimal Functional Impairment)

• Continue dupilumab and treat through symptoms with NSAIDs or short-term corticosteroids 3
• Monitor for progression at each follow-up visit 3

Moderate-to-Severe Disease (Significant Functional Impairment)

• Discontinue dupilumab immediately if symptoms are severe or refractory to symptomatic treatment 3
• Switch to tralokinumab (IL-13-specific inhibitor) as first alternative—all 15 patients in a 2025 case series achieved resolution of arthralgia without recurrence while maintaining AD control 5
• Consider JAK inhibitors (upadacitinib) as second alternative if tralokinumab is unavailable or ineffective, as this successfully treated refractory dupilumab-induced inflammatory arthritis in published cases 4, 3

Resolution Timeline

• Most patients experience full resolution within weeks following dupilumab discontinuation 3
• Symptoms may persist for up to 12 weeks in some cases even after stopping dupilumab 4

Critical Clinical Pitfalls

Diagnostic Considerations

• Obtain inflammatory markers (ESR, CRP) and autoimmune serologies (RF, anti-CCP, ANA, HLA-B27) to rule out underlying rheumatologic disease 4
• Dupilumab-associated arthritis typically presents with negative autoimmune serologies 4
• Do not assume all joint pain in dupilumab patients is drug-related—evaluate for alternative etiologies 2

Important Caveat

• The 2025 meta-analysis found no statistically significant increased risk of joint pain with dupilumab compared to controls (RR 0.68,95% CI: 0.29-1.58, P=0.31), suggesting the absolute risk may be lower than case reports suggest 2
• However, the clinical significance of symptomatic arthralgia when it does occur warrants proactive surveillance regardless of statistical significance 2

Tralokinumab as Preferred Alternative

• Tralokinumab selectively inhibits IL-13 only, avoiding the IL-4 blockade that may trigger the Th17-dominant response responsible for arthralgia 5
• This makes it the mechanistically superior choice for patients who develop dupilumab-associated joint symptoms while still requiring biologic therapy for AD 5