Efalizumab

Efalizumab
Identifier
External IDs	CAS number : 214745-43-4;
Drug information
ATC code	L04 AA21
DrugBank	DB00095
Drug class	Monoclonal antibody , immunosuppressant

Efalizumab is a drug in the group of selective immunosuppressants that has been used in the treatment of moderate to severe psoriasis . Efalizumab is a recombinant humanized monoclonal antibody and works by suppressing inflammatory reactions .

In the EU , efalizumab was marketed as an active component of a drug by MerckSerono under the trade name Raptiva from 2004 to 2009 .

Admission

Efalizumab was approved in the EU in 2004 for the treatment of moderate to severe plaque- type psoriasis vulgaris (psoriasis) . Efalizumab should only be given to patients who either did not respond to other treatments, for whom these treatments were contraindicated or who could not tolerate them.

In February 2009 the European Medicines Agency recommended suspending approval due to an increased risk of progressive multifocal leukoencephalopathy (PML). At the same time, the manufacturer recommended that efalizumab no longer be prescribed to new patients. The manufacturer then informed the European Medicines Agency in May 2009 that it had applied to the European Commission to withdraw the approval. The European Commission complied with the recommendation of the European Medicines Agency and the manufacturer's application on June 9, 2009.

In the USA , the local drug authority first asked the manufacturer to develop a suitable risk management system after the PML cases became known . The manufacturer responded with a voluntary withdrawal from the market, which was completed by June 2009. It is not known whether the US agency has formally revoked the approval in the meantime.

Mode of action

Efalizumab exerts its anti-inflammatory effect when the antibody selectively attaches itself to the CD11a subunit of a leukocyte surface protein (LFA-1, leukocyte function antigen-1 ) and thus blocks it. This has the consequence that the normally occurring bond between LFA-1 and ICAM-1 ( intercellular adhesion molecule-1 ) is prevented. The activation of T lymphocytes and the adhesion of T lymphocytes to endothelial cells are thus prevented. This prevents the activated T lymphocytes from escaping from the vessels into the skin. The result is a lessening of the symptoms of psoriasis.

Efalizumab was injected subcutaneously and was usually given once a week for 12 weeks. If, after this time, the patient showed an improvement in the complexion of at least 50%, the therapy could be continued. According to the results of a long-term study, about 80% of the treated patients achieved such a result after 12 weeks. This study was also able to show that efalizumab was effective and tolerable over a three-year therapy period.

Side effects

The suppression of the immune reaction can promote infections. The pivotal studies showed an increased rate of severe infections in the treatment group. The use of efalizumab was contraindicated in patients with active tuberculosis or other severe infections .

One death from aseptic meningitis and at least three cases of PML have been reported while efalizumab was available.

Studies

The approval of efalizumab was based on four controlled clinical studies that examined its effectiveness over 12 weeks. After correction for the placebo effects, around a quarter of the patients achieved an improvement in the PASI score of at least 75%. Treating patients with moderate to severe psoriasis for 12 weeks is also believed to have improved the patient's quality of life.

Comparative studies with other psoriasis therapies were not available until the market was withdrawn.

Pharmaco-economic evaluation

A 2006 pharmacoeconomic assessment concluded that efalizumab, while effective, was beneficial in UK healthcare conditions only in those patients who had a poor quality of life prior to starting treatment or who had a poor quality of life hospital admission was required.

literature

K. Schmitt-Rau, S. Jahn: Efalizumab. In: S. Duebel (Ed.): Handbook of Therapeutic Antibodies. Chapter 5, VCH Wiley Verlag, Weinheim 2007.
CL Leonardi, KA Papp, KB Gordon u. a .: Extended efalizumab therapy improves chronic plaque psoriasis: results from a randomized phase III trial. In: J Am Acad Dermatol. 52, 2005, pp. 425-433. PMID 15761420
A. Menter, K. Gordon, W. Carey et al. a .: Efficacy and safety observed during 24 weeks of efalizumab therapy in patients with moderate to severe plaque psoriasis. In: Arch Dermatol. 141, 2005, pp. 31-38. PMID 15655139

Web links

Public Assessment Report (EPAR) of the European Medicines Agency (EMA) for: Efalizumab

Individual evidence

^ European Medicines Agency (February 19, 2009). European Medicines Agency recommends suspension of the marketing authorization of Raptiva (efalizumab).
↑ ^a ^b Press release: European Medicines Agency recommends suspension of marketing authorization for Raptiva. (PDF; 31 kB) Merck KAaG, February 19, 2009; Retrieved February 20, 2009.
↑ EU-wide recall of Raptiva (efalizumab) to be initiated. European Medicines Agency, press release June 8, 2009.
↑ Public Statement on Raptiva (efalizumab) . European Medicines Agency, August 3, 2009.
↑ Raptiva (efalizumab) in February 2009. MedWatch: The FDA Safety Information and Adverse Event Reporting Program; Retrieved August 10, 2009.
↑ ^a ^b Sepsis and lethal death after therapy with efalizumab (Raptiva). Medicines Commission of the German Medical Association. In: Dtsch Arztebl. , 105, 2008, pp. A535-A537.
^ European Medicines Agency (October 2007). European Public Assessment Report (EPAR). Raptiva. Summary of the EPAR for the public.
↑ JP Ortonne, N. Shear, S. Shumack et al. a .: Impact of efalizumab on patient-reported outcomes in high-need psoriasis patients: results of the international, randomized, placebo-controlled Phase III Clinical Experience Acquired with Raptiva (CLEAR) trial. In: BMC Dermatol. 5, 2005, p. 13. PMID 16359548 , PMC 1343580 (free full text).
↑ N. Woolacott, N. Hawkins, A. Mason et al. a .: Etanercept and efalizumab for the treatment of psoriasis: a systematic review. In: Health Technol Assess. 10, 2006, pp. 1-233. PMID 17083854 .

[EMEA-1] European Medicines Agency (February 19, 2009). European Medicines Agency recommends suspension of the marketing authorization of Raptiva (efalizumab).

[Merck-2] Press release: European Medicines Agency recommends suspension of marketing authorization for Raptiva. (PDF; 31 kB) Merck KAaG, February 19, 2009; Retrieved February 20, 2009.

[3] EU-wide recall of Raptiva (efalizumab) to be initiated. European Medicines Agency, press release June 8, 2009.

[4] Public Statement on Raptiva (efalizumab) . European Medicines Agency, August 3, 2009.

[5] Raptiva (efalizumab) in February 2009. MedWatch: The FDA Safety Information and Adverse Event Reporting Program; Retrieved August 10, 2009.

[Arzneimittelkommission-6] Sepsis and lethal death after therapy with efalizumab (Raptiva). Medicines Commission of the German Medical Association. In: Dtsch Arztebl. , 105, 2008, pp. A535-A537.

[7] European Medicines Agency (October 2007). European Public Assessment Report (EPAR). Raptiva. Summary of the EPAR for the public.

[8] JP Ortonne, N. Shear, S. Shumack et al. a .: Impact of efalizumab on patient-reported outcomes in high-need psoriasis patients: results of the international, randomized, placebo-controlled Phase III Clinical Experience Acquired with Raptiva (CLEAR) trial. In: BMC Dermatol. 5, 2005, p. 13. PMID 16359548 , PMC 1343580 (free full text).

[9] N. Woolacott, N. Hawkins, A. Mason et al. a .: Etanercept and efalizumab for the treatment of psoriasis: a systematic review. In: Health Technol Assess. 10, 2006, pp. 1-233. PMID 17083854 .