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  • UvA-DARE is a service provided by the library of the University of Amsterdam (http://dare.uva.nl)

    UvA-DARE (Digital Academic Repository)

    Atopic dermatitis: epidemiology & off-label therapy

    Schram, M.E.

    Link to publication

    Citation for published version (APA): Schram, M. E. (2011). Atopic dermatitis: epidemiology & off-label therapy.

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    Download date: 12 Feb 2021

    https://dare.uva.nl/personal/pure/en/publications/atopic-dermatitis-epidemiology--offlabel-therapy(e7f19487-ca48-4fee-b9c3-78d71dc813c1).html

  • ME Schram

    PhI Spuls

    JD Bos

    Off-label use of efalizumab in dermatology. Expert Review of Dermatology 2010;5:535-47

  • 5.2 Off-label use Of efalizumab in DermatOlOGy : a systematiC review

  • SUMMARY

    In reaction to the marketing suspension recommended by the European Medicines Agency, Genentech announced the voluntary withdrawal of efalizumab. Since June 8, 2009, efalizumab has been unavailable. Despite the fact that the use of efalizumab is now ceased, results of studies with efalizumab will remain relevant, especially about its use in an off-label setting for indications other then chronic plaque psoriasis. New biologics as well as chemicals are being developed targeting similar t-cell-mediated pathways. Indications for these new compounds other than psoriasis could be selected based on this systematic review. With this article we aimed to summarize the evidence of effectiveness, efficacy and safety of efalizumab in off-label dermatological use and to illustrate the time scale in which drugs are offered off-label to dermatological patients. We found some evidence supporting the effectiveness of efalizumab in palmoplantar pustulosis, atopic dermatitis, lichen planus and cutaneous lupus erythematosus. In total, 12 serious adverse events occurred, one due to an infection. Efalizumab was given off-label within half a year after registration of the drug for plaque psoriasis.

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    INtRoDUCtIoN

    In reaction to the marketing suspension recommended by the European Medicines Agency (EMA), Genentech announced the voluntary withdrawal of efalizumab. Since June 8, 2009, efalizumab is no longer available. The reason for this withdrawal is that the benefit of the drug in psoriasis is no longer considered to outweigh its risks, after four cases of progressive multifocal leukoencephalopathy (PML) in a patient population of approximately 48,000 patient-years. Although this is not an unknown side effect in different immunosuppressive treatments, the additive value of efalizumab for psoriasis on the comprehensive biological market at this point is questioned.1

    Efalizumab is a recombinant, humanized, monoclonal IgG-1 antibody that binds to CD11a, the α-subunit of leukocyte function-associated antigen-1. As such, it interferes with T-cell trafficking and T-cell activation.2 A series of randomized controlled trials (RCTs) have demonstrated the efficacy and safety of efalizumab in the treatment of chronic moderate to severe plaque psoriasis.3-8 Thus far, the longest evaluation of the efficacy and safety of systemic biological therapy in psoriasis has been a 3-year, phase III, open-label trial of continuous efalizumab therapy.9-11

    Short-term adverse events such as flu-like symptoms may be seen following the first two doses, with an incidence comparable to placebo after the third dose.12 There was no evidence of end-organ toxicity.11,12

    Efalizumab was registered for the treatment of plaque psoriasis, but was also extensively explored in an off-label setting for other, often difficult to treat, dermatological diseases. Efalizumab was suspended due to an unfavourable risk–benefit ratio in psoriasis, therefore it will probably be unavailable for other dermatological diseases also.

    However, in this article, we summarize the evidence of safety, efficacy and effectiveness of treatment with efalizumab in patients with dermatological diseases other than psoriasis and show the time scale in which efalizumab was used off-label in dermatology.

    MEtHoDS

    Inclusion and exclusion criteria RCTs, case reports and pilot studies in which patients with dermatological diseases other than plaque psoriasis were treated with efalizumab were assessed for eligibility.

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    Studies that reported efficacy, effectiveness and/or safety were included. Reviews, unpublished articles or poster presentations were excluded. No restrictions were imposed regarding age, gender, skin type and number of subjects in a study. No language restrictions were applied. Double publications were excluded.

    Literature search Between December 2008 and January 2009, a literature search in MEDLINE, EMBASE and CENTRAL was performed (Table 1). As the main search strategy, ‘efalizumab’ and synonyms were used. An additional search was carried out combining the search term ‘monoclonal antibodies’ with the different dermatological diseases found in the first search supplemented with Sjögren’s disease and pyoderma gangrenosum; diseases that may be T-cell-mediated, but were not found in the initial search. There was no limit to the date of the publication. References of all relevant articles found were checked in order to find additional articles.

    Study selection & data extraction All articles with a title and abstract considering efalizumab treatment in dermatological patients other than psoriasis were selected by the first author

    table 1. Search strategy for MEDLINE and EMBASE

    meDline

    1. (“efalizumab”[Substance Name] OR “efalizumab”[All Fields]) OR (“efalizumab”[Substance Name] OR “efalizumab”[All Fields] OR “raptiva”[All Fields]) OR hu1124[All Fields] OR CD11a[All Fields] OR xanelim[All Fields]

    2. “antibodies, monoclonal”[MeSH Terms] OR “monoclonal antibodies”[All Fields] 3. “dermatitis, atopic”[MeSH Terms] OR (“dermatitis”[All Fields] AND “atopic”[All Fields]) OR

    “atopic dermatitis”[All Fields] OR (“atopic”[All Fields] AND “dermatitis”[All Fields]) 4. “palmoplantar pustulosis”[All Fields] OR “palmoplantar pustular psoriasis”[All Fields] OR “foot

    psoriasis”[All Fields] 5. “Pityriasis Rubra Pilaris”[Mesh] OR “Pityriasis Rubra Pilaris”[All Fields] 6. “Lichen Planus”[Mesh] AND “Lichen Planus”[All Fields] 7. “Alopecia Areata”[Mesh] AND “Alopecia Areata”[All Fields] 8. “Stomatitis, Aphthous”[Mesh] AND “Stomatitis, Aphthous”[All Fields] 9. “Pyoderma Gangrenosum”[Mesh] AND “Pyoderma Gangrenosum”[All Fields] 10. “Granuloma Annulare”[Mesh] AND “Granuloma Annulare”[All Fields] 11. “Dermatomyositis”[Mesh] AND “Dermatomyositis”[All Fields] 12. “Vitiligo”[Mesh] AND “Vitiligo”[All Fiels] 13. “Sjogren’s Syndrome”[Mesh] AND “Sjogren’s Syndrome”[All fields] 14. “Lupus Erythematosus, Discoid”[Mesh] OR “lupus erythematosus”[All Fields] 15. 2 AND (3 OR 4 OR 5 OR 6 OR 7 OR 8 OR 9 OR 10 OR 11 OR 12 OR 13 OR 14) 16. 1 AND 15

    Continued on next page

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    table 1. Continued

    embase

    1. Efalizumab/ 2. hu1124.mp. or monoclonal antibody CD11a/ or xanelim.mp. 3. 1 or 2 4. exp Monoclonal Antibody/ 5. Atopic Dermatitis/ 6. ((atopic$ or intrins$ or allergic$) adj3 (dermatit$ or eczem$)).tw. 7. 5 or 6 8. exp Pustular Psoriasis/ or exp Pustulosis Palmoplantaris/or exp Hand and foot psoriasis/ 9. Pityriasis Rubra Pilaris.mp. or exp Pityriasis Rubra Pilaris/ 10. hidradenitis suppurativa.mp. or exp Suppurative Hidradenitis/ 11. lichen planus.mp. or exp Lichen Planus/ 12. aphthous stomatitis.mp. or exp Aphthous Stomatitis/ 13. pyoderma gangrenosum.mp. or exp Pyoderma Gangrenosum/ 14. granuloma annulare.mp. or exp Granuloma Annulare/ 15. vitiligo.mp. or exp vitiligo/ 16. cutaneous lupus erythematosus.mp. or exp Skin Lupus Erythematosus/ 17. sjogren.mp. or exp Sjoegren Syndrome/ 18. 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15 or 16 or 17 19. 4 AND 18 20. 3 AND 19

    (M.S.) for relevance. To determine eligibility, the full text of the selected articles was screened by two reviewers (M.S. & drs. J. La Verge).

    Data on study characteristics, efficacy, effectveness and safety were extracted by two reviewers independently (M.S. & drs. J. La Verge) using a data extraction form. Study characteristics included: dermatological disease concerned, design of the study, number of patients included, dose of efalizumab and duration of study. Disagreements about study selection and data extraction were