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Alefacept significantly reduces psoriasis area and severity in people with chronic plaque psoriasis
EVIDENCE -BASED CLINICAL PR AC TICE
Alefacept significantly reduces psoriasis area and severity in people with chronic plaque psoriasis Abstracted from: Ellis C, Krueger GG.Treatment of chronic plaque psoriasis by selective targeting of memory effectorT lymphocytes. N Engl J Med 2001; 345(4): 248 ^255.
BACKGROUND Psoriasis is a chronic auto-immune disease a¡ecting 2% of the population. T lymphocytes are involved in the in£ammatory process. Alefacept was designed to interfere with T lymphocyte activation and modify the in£ammatory process. OBJECTIVE To compare alefacept and placebo in the treatment of chronic plaque psoriasis. SETTING Twenty-two US centres; treatment in 1998. METHOD Multicentre double-blind randomised controlled trial. PARTICIPANTS Two hundred and twenty-nine 18^70 year olds with chronic plaque psoriasis diagnosed 12 months; 10% body surface a¡ected; previously received systemic therapy/phototherapy/eligible for such treatment. Principal exclusion criteria were serious hepatic/renal disease; cancer; 75% greater than ideal weight; serious infection in past 3 months. INTERVENTION Alefacept (0.025, 0.075 or 0.150 mg/kg) or placebo intravenously weekly for 12 weeks. No systemic treatment/phototherapy/potent topical agents permitted; application of moderatepotency topical agents permitted to groin, scalp, soles and palms; emollients permitted. OUTCOMES Psoriasis area-and-severity global assessment by treating physician.
index;
MAIN RESULTS At 2 weeks post-treatment, all three doses of alefacept had signi¢cantly reduced the psoriasis index compared to placebo (reduced by 38%
Commentary Psoriasis is a chronic cutaneous disease characterised by epidermal hyperproliferation and a T-cell inflammatory infiltrate in the dermis and epidermis. Psoriasis is probably a T-cell mediated & 2002 Elsevier Science Ltd. Allrights reserved doi:10.1054/ebhc.2001.0478, available online at http://www.idealibrary.com.on
for 0.025 mg/kg, 53% for 0.075 mg/kg and 53% for 0.15 mg/kg versus 21% for placebo; Po0.001). All doses of alefacept increased the number of people with 50% reduction in psoriasis index at 2 (P ¼ 0.001) and12 weeks (P ¼ 0.020) post-treatment (see Table 1). Adverse reactions more commonly reported in alefacept than placebo were accidental injury unrelated to study, dizziness, nausea, chills and cough (seeTable 2). AUTHORS’ CONCLUSIONS Compared to placebo, 12 weeks of alefacept treatment signi¢cantly reduced psoriasis area and severity in people with chronic plaque psoriasis. Table 1 Proportion with psoriasis area-severity index 450% reduction 2 and 12 weeks after treatment with alefacept or placebo Psoriasis index 450% score reduction 2 weeks post-treatment 12 weeks post-treatment
0.025 mg 0.075 mg 0.150 mg Placebo P% value alefacept alefacept alefacept (n ¼ 59) % % % (n ¼ 57) (n ¼ 55) (n ¼ 58) 36
60
56
27
0.001
47
63
42
32
0.02
Table 2 Adverse reactions after treatment with alefacept or placebo Adverse reaction
Alefacept %
Placebo %
Accidental injury Dizziness Nausea Chills Cough Infection related
13 9 6 5 5 45
5 2 0 0 0 53
autoimmune disease. This study is important as it reports the safety and efficacy of a new specific immune targetted therapy for psoriasis, alefacept. Alefacept abrogates T-cell activation by inhibiting the interaction between CD2 and leukocyte-functionassociated antigen-3 (LFA-3). In psoriasis, this effect is seen as Evidence-based Healthcare (2002) 6, 39^ 40
39
selective impairment of memory-effector (CD45RO+) T-cell activation.This was a randomised double-blind placebo-controlled multiple dose study in patients with moderate to severe psoriasis. Alefacept, delivered as a weekly intravenous injection over12 weeks, was significantly more effective than placebo in improving psoriasis. The effect was dose related and the drug was safe with short-term use. 24% of treated patients achieved clearance and in these patients remission was often prolonged. This study shows that specific, immune targeted therapies may be safe and effective in psoriasis; however, only 24% of patients achieved clearance after 12 weeks of an intravenous injection necessitating monitoring of various haematological parameters including the CD4 count.This may deter widespread use of this drug in clinical practice as patients may expect a higher clearance rate for a systemic drug with potential side-effects.
40
Evidence-based Healthcare (2002) 6, 39^ 40
The corollary is that the majority of patients achieved more than a 50% decrease in physical severity of psoriasis. Alefecept offers a much needed new therapeutic option for the treatment of psoriasis. A once weekly injection may be preferable to other treatment modalities for severe psoriasis with similar safety and efficacy profiles. It remains to be determined as to whether alefacept will be used as a drug to induce remission or to maintain remission which has been induced by another modality. Dr B. Kirby University of Manchester, Manchester, UK Note: Dr Kirby was a blinded laboratory-assisting physician in a phase III trial of alefacept for psoriasis.
& 2002 Elsevier Science Ltd. All rights reserved
Alefacept significantly reduces psoriasis area and severity in people with chronic plaque psoriasis Abstracted from: Ellis C, Krueger GG.Treatment of chronic plaque psoriasis by selective targeting of memory effectorT lymphocytes. N Engl J Med 2001; 345(4): 248 ^255.
BACKGROUND Psoriasis is a chronic auto-immune disease a¡ecting 2% of the population. T lymphocytes are involved in the in£ammatory process. Alefacept was designed to interfere with T lymphocyte activation and modify the in£ammatory process. OBJECTIVE To compare alefacept and placebo in the treatment of chronic plaque psoriasis. SETTING Twenty-two US centres; treatment in 1998. METHOD Multicentre double-blind randomised controlled trial. PARTICIPANTS Two hundred and twenty-nine 18^70 year olds with chronic plaque psoriasis diagnosed 12 months; 10% body surface a¡ected; previously received systemic therapy/phototherapy/eligible for such treatment. Principal exclusion criteria were serious hepatic/renal disease; cancer; 75% greater than ideal weight; serious infection in past 3 months. INTERVENTION Alefacept (0.025, 0.075 or 0.150 mg/kg) or placebo intravenously weekly for 12 weeks. No systemic treatment/phototherapy/potent topical agents permitted; application of moderatepotency topical agents permitted to groin, scalp, soles and palms; emollients permitted. OUTCOMES Psoriasis area-and-severity global assessment by treating physician.
index;
MAIN RESULTS At 2 weeks post-treatment, all three doses of alefacept had signi¢cantly reduced the psoriasis index compared to placebo (reduced by 38%
Commentary Psoriasis is a chronic cutaneous disease characterised by epidermal hyperproliferation and a T-cell inflammatory infiltrate in the dermis and epidermis. Psoriasis is probably a T-cell mediated & 2002 Elsevier Science Ltd. Allrights reserved doi:10.1054/ebhc.2001.0478, available online at http://www.idealibrary.com.on
for 0.025 mg/kg, 53% for 0.075 mg/kg and 53% for 0.15 mg/kg versus 21% for placebo; Po0.001). All doses of alefacept increased the number of people with 50% reduction in psoriasis index at 2 (P ¼ 0.001) and12 weeks (P ¼ 0.020) post-treatment (see Table 1). Adverse reactions more commonly reported in alefacept than placebo were accidental injury unrelated to study, dizziness, nausea, chills and cough (seeTable 2). AUTHORS’ CONCLUSIONS Compared to placebo, 12 weeks of alefacept treatment signi¢cantly reduced psoriasis area and severity in people with chronic plaque psoriasis. Table 1 Proportion with psoriasis area-severity index 450% reduction 2 and 12 weeks after treatment with alefacept or placebo Psoriasis index 450% score reduction 2 weeks post-treatment 12 weeks post-treatment
0.025 mg 0.075 mg 0.150 mg Placebo P% value alefacept alefacept alefacept (n ¼ 59) % % % (n ¼ 57) (n ¼ 55) (n ¼ 58) 36
60
56
27
0.001
47
63
42
32
0.02
Table 2 Adverse reactions after treatment with alefacept or placebo Adverse reaction
Alefacept %
Placebo %
Accidental injury Dizziness Nausea Chills Cough Infection related
13 9 6 5 5 45
5 2 0 0 0 53
autoimmune disease. This study is important as it reports the safety and efficacy of a new specific immune targetted therapy for psoriasis, alefacept. Alefacept abrogates T-cell activation by inhibiting the interaction between CD2 and leukocyte-functionassociated antigen-3 (LFA-3). In psoriasis, this effect is seen as Evidence-based Healthcare (2002) 6, 39^ 40
39
selective impairment of memory-effector (CD45RO+) T-cell activation.This was a randomised double-blind placebo-controlled multiple dose study in patients with moderate to severe psoriasis. Alefacept, delivered as a weekly intravenous injection over12 weeks, was significantly more effective than placebo in improving psoriasis. The effect was dose related and the drug was safe with short-term use. 24% of treated patients achieved clearance and in these patients remission was often prolonged. This study shows that specific, immune targeted therapies may be safe and effective in psoriasis; however, only 24% of patients achieved clearance after 12 weeks of an intravenous injection necessitating monitoring of various haematological parameters including the CD4 count.This may deter widespread use of this drug in clinical practice as patients may expect a higher clearance rate for a systemic drug with potential side-effects.
40
Evidence-based Healthcare (2002) 6, 39^ 40
The corollary is that the majority of patients achieved more than a 50% decrease in physical severity of psoriasis. Alefecept offers a much needed new therapeutic option for the treatment of psoriasis. A once weekly injection may be preferable to other treatment modalities for severe psoriasis with similar safety and efficacy profiles. It remains to be determined as to whether alefacept will be used as a drug to induce remission or to maintain remission which has been induced by another modality. Dr B. Kirby University of Manchester, Manchester, UK Note: Dr Kirby was a blinded laboratory-assisting physician in a phase III trial of alefacept for psoriasis.
& 2002 Elsevier Science Ltd. All rights reserved