An indirect comparison of long-term efficacy of every-2-week dosing vs. recommended dosing of ixekizumab in patients who had static Physician's Global Assessment > 1 at week 12.
Journal
The British journal of dermatology
ISSN: 1365-2133
Titre abrégé: Br J Dermatol
Pays: England
ID NLM: 0004041
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
accepted:
18
09
2019
pubmed:
24
9
2019
medline:
15
5
2021
entrez:
24
9
2019
Statut:
ppublish
Résumé
Long-term efficacy and safety of ixekizumab [160 mg at week 0, then 80 mg every 2 weeks (Q2W) for 12 weeks, followed by every 4 weeks (Q4W) thereafter (i.e. Q2W/Q4W), which is the labelled psoriasis dosing where approved, except in Japan] have been established for the treatment of adults with moderate-to-severe plaque psoriasis. However, some patients may benefit from remaining on Q2W dosing beyond 12 weeks. Among patients who had static Physician's Global Assessment (sPGA) > 1 at week 12, efficacy through week 52 of continuous Q2W dosing in the IXORA-P study was compared indirectly with Q2W/Q4W in the integrated data from the UNCOVER-1, UNCOVER-2 and UNCOVER-3 studies. The continuous Q4W dose group, which had comparable results across studies, was used as the common comparator. In the IXORA-P study, among patients with sPGA > 1 at week 12, 64% of patients in the continuous Q2W group achieved sPGA ≤ 1 at week 52, which was statistically significantly higher than the 36% of patients with sPGA > 1 in the Q2W/Q4W group based on the integrated data from the UNCOVER studies (P = 0·0007). There were no clinically meaningful differences in frequencies of safety events between patients with sPGA ≤ 1 and patients with sPGA > 1 at week 12 in the IXORA-P study. Among patients who did not have clear or almost clear skin at week 12, nearly 30% more patients who were treated continuously with ixekizumab Q2W in IXORA-P had clear or almost clear skin at week 52 when compared indirectly with those who were treated using the labelled psoriasis dosing in integrated UNCOVER studies. What's already known about this topic? Most patients with moderate-to-severe psoriasis who were given the labelled psoriasis dosing of ixekizumab [160-mg loading dose at week 0, 80 mg every 2 weeks (Q2W) through week 12, and 80 mg every 4 weeks (QW4) thereafter] respond quickly with a high percentage of skin clearance. Additionally, patients who achieve static Physician's Global Assessment (sPGA) ≤ 1 by week 12 tend to maintain this response, even after switching to Q4W. What does this study add? Here, we assessed whether patients with sPGA > 1 at week 12 benefited from receiving more frequent dosing beyond the first 12 weeks. The results showed that Q2W dosing beyond 12 weeks resulted in more patients achieving sPGA ≤ 1 by week 52 than the labelled psoriasis dosing among patients with sPGA > 1 at week 12.
Sections du résumé
BACKGROUND
Long-term efficacy and safety of ixekizumab [160 mg at week 0, then 80 mg every 2 weeks (Q2W) for 12 weeks, followed by every 4 weeks (Q4W) thereafter (i.e. Q2W/Q4W), which is the labelled psoriasis dosing where approved, except in Japan] have been established for the treatment of adults with moderate-to-severe plaque psoriasis. However, some patients may benefit from remaining on Q2W dosing beyond 12 weeks.
METHODS
Among patients who had static Physician's Global Assessment (sPGA) > 1 at week 12, efficacy through week 52 of continuous Q2W dosing in the IXORA-P study was compared indirectly with Q2W/Q4W in the integrated data from the UNCOVER-1, UNCOVER-2 and UNCOVER-3 studies. The continuous Q4W dose group, which had comparable results across studies, was used as the common comparator.
RESULTS
In the IXORA-P study, among patients with sPGA > 1 at week 12, 64% of patients in the continuous Q2W group achieved sPGA ≤ 1 at week 52, which was statistically significantly higher than the 36% of patients with sPGA > 1 in the Q2W/Q4W group based on the integrated data from the UNCOVER studies (P = 0·0007). There were no clinically meaningful differences in frequencies of safety events between patients with sPGA ≤ 1 and patients with sPGA > 1 at week 12 in the IXORA-P study.
CONCLUSIONS
Among patients who did not have clear or almost clear skin at week 12, nearly 30% more patients who were treated continuously with ixekizumab Q2W in IXORA-P had clear or almost clear skin at week 52 when compared indirectly with those who were treated using the labelled psoriasis dosing in integrated UNCOVER studies. What's already known about this topic? Most patients with moderate-to-severe psoriasis who were given the labelled psoriasis dosing of ixekizumab [160-mg loading dose at week 0, 80 mg every 2 weeks (Q2W) through week 12, and 80 mg every 4 weeks (QW4) thereafter] respond quickly with a high percentage of skin clearance. Additionally, patients who achieve static Physician's Global Assessment (sPGA) ≤ 1 by week 12 tend to maintain this response, even after switching to Q4W. What does this study add? Here, we assessed whether patients with sPGA > 1 at week 12 benefited from receiving more frequent dosing beyond the first 12 weeks. The results showed that Q2W dosing beyond 12 weeks resulted in more patients achieving sPGA ≤ 1 by week 52 than the labelled psoriasis dosing among patients with sPGA > 1 at week 12.
Substances chimiques
Antibodies, Monoclonal, Humanized
0
ixekizumab
BTY153760O
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
52-59Subventions
Organisme : Eli Lilly and Company
Pays : International
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2019 British Association of Dermatologists.
Références
Papp KA, Leonardi CL, Blauvelt A et al. Ixekizumab treatment for psoriasis: Integrated efficacy analysis of three double-blinded, controlled studies (UNCOVER-1, UNCOVER-2, UNCOVER-3). Br J Dermatol 2018; 178:674-81.
Gordon KB, Blauvelt A, Papp KA et al. Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis. N Engl J Med 2016; 375:345-56.
Cassano N, Loconsole F, Miracapillo A et al. Treatment of psoriasis with different dosage regimens of etanercept: preliminary results from the Tαranta Plastic Study Group. Int J Immunopathol Pharmacol 2010; 23:797-802.
Leonardi C, Strober B, Gottlieb AB et al. Long-term safety and efficacy of etanercept in patients with psoriasis: an open-label study. J Drugs Dermatol 2010; 9:928-37.
Gordon KB, Langley RG, Leonardi C et al. Clinical response to adalimumab treatment in patients with moderate to severe psoriasis: double-blind, randomized controlled trial and open-label extension study. J Am Acad Dermatol 2006; 55:598-606.
Papp KA, Langley RG, Lebwohl M et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2). Lancet 2008; 371:1675-84.
Langley RG, Papp K, Gooderham M et al. Efficacy and safety of continuous every 2-week dosing of ixekizumab over 52 weeks in patients with moderate-to-severe plaque psoriasis in a randomized phase 3 trial (IXORA-P). Br J Dermatol 2018; 178:1315-1323.
Griffiths CE, Reich K, Lebwohl M et al. Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis (UNCOVER-2 and UNCOVER-3): results from two phase 3 randomised trials. Lancet 2015; 386:541-51.
Bucher HC, Guyatt GH, Griffith LE, Walter SD. The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials. J Clin Epidemiol 1997; 50:683-91.
Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews of Interventions. Hoboken, NJ: John Wiley & Sons, 2011.
Lebwohl M, Yeilding N, Szapary P et al. Impact of weight on the efficacy and safety of ustekinumab in patients with moderate to severe psoriasis: rationale for dosing recommendations. J Am Acad Dermatol 2010; 63:571-9.
Puig L. Obesity and psoriasis: body weight and body mass index influence the response to biological treatment. J Eur Acad Dermatol Venereol 2011; 25:1007-11.
Gottlieb AB, Lacour JP, Korman N et al. Treatment outcomes with ixekizumab in patients with moderate-to-severe psoriasis who have or have not received prior biological therapies: an integrated analysis of two phase III randomized studies. J Eur Acad Dermatol Venereol 2017; 31:679-85.