What is the role of Infliximab (chimeric monoclonal antibody) in treating pustular psoriasis?

Infliximab for Pustular Psoriasis

Infliximab may be recommended as a monotherapy treatment option for pustular psoriasis, with particularly strong evidence supporting its use in severe generalized pustular psoriasis where it demonstrates rapid efficacy and generally positive results. 1

Strength of Recommendation

The most recent joint AAD-NPF guidelines (2019) provide a Grade C recommendation for infliximab in pustular psoriasis, indicating it "may be recommended" for other subtypes (pustular or erythrodermic) of moderate-to-severe psoriasis. 1 This is a weaker recommendation compared to the Grade A recommendation for plaque psoriasis, reflecting the limited evidence base consisting primarily of case reports and small case series rather than randomized controlled trials. 1

Clinical Evidence and Efficacy

Generalized Pustular Psoriasis

Infliximab demonstrates rapid and often complete disease clearance in severe generalized pustular psoriasis. 1, 2 The British Association of Dermatologists reports that infliximab has been used with generally positive results, including:

• Complete disease clearance allowing withdrawal of all conventional systemic treatments in documented cases 1
• Two of three patients in a follow-up study achieved complete clearance with infliximab treatment 1
• Significant improvement within three days of treatment initiation in therapy-resistant cases 3

Long-term management data suggests infliximab efficacy is optimized with infusions every 6-8 weeks combined with methotrexate, which may decrease infusion reactions and increase efficacy. 4 In clinical practice, 87% of patients required more than the standard 5 mg/kg every 8 weeks dosing to maintain clearance. 5

Localized Pustular Psoriasis (Acropustulosis)

For acropustulosis of Hallopeau, infliximab is reasonable to recommend when the condition has a major impact on quality of life. 2 At least 10 case reports document significant benefit from TNF antagonists including infliximab for this rare but disabling condition, contrasting with only two reports of treatment failure. 1 One review found complete clearance in 2 of 2 patients with severe acropustulosis treated with infliximab for over one year. 5

Dosing Recommendations

Standard dosing is 5 mg/kg infused at weeks 0,2, and 6, then every 8 weeks thereafter. 1 However:

• Dose intensification up to 10 mg/kg and/or more frequent intervals (as often as every 4 weeks) may be needed for better disease control (Grade B recommendation). 1
• Real-world data shows 87% of psoriasis patients require more aggressive dosing than the standard regimen to maintain clearance. 5

Combination Therapy Strategies

Infliximab may be combined with methotrexate to augment efficacy (Grade B recommendation), which appears particularly beneficial for long-term management of generalized pustular psoriasis. 1, 4

Sequential therapy using infliximab for rapid induction followed by etanercept for maintenance represents a novel approach that combines fast onset with potentially lower risk for severe adverse events. 6 This strategy has been successfully employed in generalized pustular psoriasis. 1, 6

Combination with topical high-potency corticosteroids with or without vitamin D analogues can be recommended (Grade B recommendation). 1

Important Clinical Caveats

Contraindication in Palmoplantar Pustulosis

TNF antagonists including infliximab should be avoided in chronic palmoplantar pustulosis, as they may exacerbate this condition. 1, 2 This represents a critical distinction from generalized pustular psoriasis and acropustulosis where infliximab is beneficial.

Relapse Patterns

Upon discontinuation of infliximab, relapse is common but not universal. 1 In the British Association of Dermatologists case series, two of three patients relapsed after stopping infliximab following variable numbers of infusions, while disease remission was maintained in one patient. 1

Pediatric Use

Infliximab has shown success in juvenile generalized pustular psoriasis, with no recurrence during 12 months of follow-up in documented cases, though close monitoring for adverse effects (including herpes zoster) is essential. 7

Practical Algorithm for Use

1. Confirm diagnosis of generalized pustular psoriasis or acropustulosis with major quality of life impact 1, 2
2. Exclude palmoplantar pustulosis as the primary diagnosis 1, 2
3. Initiate standard dosing (5 mg/kg at weeks 0,2,6, then every 8 weeks) 1
4. Consider adding methotrexate for long-term management and to reduce infusion reactions 4, 5
5. Intensify dosing (increase frequency to every 4-6 weeks or dose to 10 mg/kg) if inadequate response 1, 4, 5
6. For maintenance, consider transitioning to etanercept after achieving remission with infliximab 6

Comparative Context

While infliximab has the strongest evidence base for pustular psoriasis among TNF antagonists, etanercept at 50 mg biweekly (not 25 mg) has also demonstrated efficacy in generalized pustular psoriasis with maintenance of response up to 48 weeks. 1, 2 However, infliximab's more rapid onset makes it preferable for severe acute presentations. 2, 3, 6