Dataset Information

A randomized, double-blind, placebo-controlled study to evaluate the addition of methotrexate to etanercept in patients with moderate to severe plaque psoriasis.

ABSTRACT:

Background

Etanercept plus methotrexate combination therapy has not been adequately investigated in psoriasis.

Objectives

To evaluate etanercept plus methotrexate vs. etanercept monotherapy in patients with moderate to severe plaque psoriasis who had not failed prior methotrexate or tumour necrosis factor-inhibitor therapy.

Methods

Patients received etanercept 50 mg twice weekly for 12 weeks followed by 50 mg once weekly for 12 weeks and were randomized 1 : 1 to receive methotrexate (7·5-15 mg weekly) or placebo. The primary endpoint was the proportion of patients achieving ≥75% improvement in Psoriasis Area and Severity Index (PASI 75) at week 24.

Results

In total, 239 patients were enrolled in each arm. PASI 75 was significantly higher at week 24 for the combination therapy group compared with the monotherapy group (77·3% vs. 60·3%; P < 0·0001). Other PASI improvement scores at week 12 [PASI 75, 70·2% vs. 54·3% (P = 0·01); PASI 50, 92·4% vs. 83·8% (P = 0·01); and PASI 90, 34·0% vs. 23·1% (P = 0·03)] showed similar results as did week 24 PASI 50 (91·6% vs. 84·6%; P = 0·01) and PASI 90 (53·8% vs. 34·2%; P = 0·01). Significantly more patients receiving combination therapy than monotherapy had static Physician's Global Assessment of clear/almost clear at week 12 (65·5% vs. 47·0%; P = 0·01) and week 24 (71·8% vs. 54·3%; P = 0·01). Adverse events (AEs) were reported in 74·9% and 59·8% of combination therapy and monotherapy groups, respectively; three serious AEs were reported in each arm.

Conclusions

Combination therapy with etanercept plus methotrexate had acceptable tolerability and increased efficacy compared with etanercept monotherapy in patients with moderate to severe psoriasis.

SUBMITTER: Gottlieb AB

PROVIDER: S-EPMC3504074 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Publications

A randomized, double-blind, placebo-controlled study to evaluate the addition of methotrexate to etanercept in patients with moderate to severe plaque psoriasis.

Gottlieb A B AB Langley R G RG Strober B E BE Papp K A KA Klekotka P P Creamer K K Thompson E H Z EH Hooper M M Kricorian G G

The British journal of dermatology 20120901 3

<h4>Background</h4>Etanercept plus methotrexate combination therapy has not been adequately investigated in psoriasis.<h4>Objectives</h4>To evaluate etanercept plus methotrexate vs. etanercept monotherapy in patients with moderate to severe plaque psoriasis who had not failed prior methotrexate or tumour necrosis factor-inhibitor therapy.<h4>Methods</h4>Patients received etanercept 50 mg twice weekly for 12 weeks followed by 50 mg once weekly for 12 weeks and were randomized 1 : 1 to receive met ...[more]

PMID: 22533447

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Project description:BackgroundPlaque psoriasis affects children and adults, but treatment options for paediatric psoriasis are limited.ObjectivesTo evaluate the efficacy and safety of ixekizumab (IXE), a high-affinity monoclonal antibody that selectively targets interleukin-17A, for moderate-to-severe paediatric psoriasis.MethodsIn a randomized, double-blind, placebo-controlled, phase III study (IXORA-PEDS), patients aged 6 to < 18 years with moderate-to-severe plaque psoriasis were randomized 2 : 1 to weight-based dosing of IXE every 4 weeks (IXE Q4W, n = 115) or placebo (n = 56) through week 12, followed by open-label IXE Q4W. Coprimary endpoints were the proportions of patients at week 12 achieving ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) and those achieving a static Physician's Global Assessment score of 0 or 1 (sPGA 0,1).ResultsIXE was superior (P < 0·001) to placebo for both coprimary endpoints of PASI 75 (IXE Q4W, 89%; placebo, 25%) and sPGA (0,1) (IXE Q4W, 81%; placebo, 11%). IXE was also superior for all gated secondary endpoints, including PASI 75 and sPGA (0,1) at week 4, improvement in itch, and complete skin clearance. IXE Q4W provided significant (P < 0·001) improvements vs. placebo in quality of life and clearance of scalp and genital psoriasis. Responses at week 12 were sustained or further improved through week 48. Through week 12, 45% (placebo) and 56% (IXE) of patients reported treatment-emergent adverse events. One serious adverse event was reported (IXE), one patient discontinued due to an adverse event (placebo) and no deaths were reported.ConclusionsIXE was superior to placebo in the treatment of moderate-to-severe paediatric psoriasis, and the safety profile was generally consistent with that observed in adults. What is already known about this topic? Paediatric psoriasis affects approximately 1% of children and can negatively impact health-related quality of life. Treatment options for paediatric psoriasis are typically limited to off-label treatments and approved systemic biologics. Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A, is approved for moderate-to-severe plaque psoriasis in adults and was recently approved by the US Food and Drug Administration for moderate-to-severe paediatric psoriasis. What does this study add? Ixekizumab resulted in rapid and statistically significant improvements over placebo in skin involvement, itch and health-related quality of life, which persisted through 48 weeks of treatment in paediatric patients with moderate-to-severe plaque psoriasis. The safety profile of ixekizumab was generally consistent with that seen in adults. Ixekizumab may be an additional potential therapeutic option and an additional class of biologic therapy (interleukin-17A antagonist) for the treatment of moderate-to-severe paediatric psoriasis. Plain language summary available online.

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Dataset Information

A randomized, double-blind, placebo-controlled study to evaluate the addition of methotrexate to etanercept in patients with moderate to severe plaque psoriasis.

Background

Objectives

Methods

Results

Conclusions

Publications

A randomized, double-blind, placebo-controlled study to evaluate the addition of methotrexate to etanercept in patients with moderate to severe plaque psoriasis.

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