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Efficacy and Safety of Switching to Ixekizumab in Etanercept Non-Responders: A Subanalysis from Two Phase III Randomized Clinical Trials in Moderate-to-Severe Plaque Psoriasis (UNCOVER-2 and -3).
Am J Clin Dermatol. 2017 Apr; 18(2):273-280.AJ

Abstract

BACKGROUND

Patients with psoriasis who have an inadequate response to one biologic may benefit from switching to a new biologic, such as ixekizumab, a high affinity monoclonal antibody that selectively targets interleukin (IL)-17A.

OBJECTIVE

Our aim was to assess the response to ixekizumab in patients with moderate-to-severe plaque psoriasis who did not respond adequately to etanercept using a post-hoc analysis in two phase III studies.

METHODS

For the subanalyses in two phase III trials (UNCOVER-2 and -3), non-response was defined by either failure to have a static physician global assessment (sPGA) of 0/1 in UNCOVER-2 or failure to have at least 75% improvement in psoriasis area and severity index (PASI 75) in UNCOVER-3 at Week 12 of each study. Non-responders treated with twice-weekly etanercept 50 mg in the first 12 weeks received two injections of placebo at Week 12 (4-week wash-out period), followed by ixekizumab every 4 weeks (Q4W) for Weeks 16-60. Non-responders to placebo in the first 12 weeks were administered ixekizumab 160 mg at Week 12, followed by ixekizumab Q4W for Weeks 16-60.

RESULTS

After switching to ixekizumab Q4W, a substantial proportion of patients with moderate-to-severe psoriasis who did not respond to etanercept experienced rapid and durable improvement in all efficacy evaluations. Among sPGA 0/1 (UNCOVER-2) and PASI 75 (UNCOVER-3) non-responders to etanercept, 73.0% achieved sPGA 0/1 and 78.2% achieved PASI 75, respectively, after 12 weeks of ixekizumab treatment. Safety profiles in patients switched from etanercept to ixekizumab were similar to those in patients switched from placebo to ixekizumab.

CONCLUSION

Patients who were non-responders to etanercept after 12 weeks, as defined by failure to meet sPGA 0/1 (UNCOVER-2) or PASI 75 (UNCOVER-3), achieved high levels of response 12 weeks after switching to ixekizumab. Studies are registered with ClinicalTrials.gov (NCT01597245 and NCT01646177).

Links

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Authors+Show Affiliations

Blauvelt A
Oregon Medical Research Center, 9495 SW Locust St., Suite G, Portland, OR, 97223, USA. ablauvelt@oregonmedicalresearch.com.
Papp KA
K Papp Clinical Research and Probity Medical Research, Waterloo, Canada.
Griffiths CEM
Dermatology Centre, Salford Royal Hospital, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.
Puig L
Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
Weisman J
Medical Dermatology Specialists, Inc., Atlanta, GA, USA.
Dutronc Y
Eli Lilly and Company, Indianapolis, IN, USA.
Kerr LF
Eli Lilly and Company, Indianapolis, IN, USA.
Ilo D
Eli Lilly and Company, Indianapolis, IN, USA.
Mallbris L
Eli Lilly and Company, Indianapolis, IN, USA.
Augustin M
Institute for Health Services Research in Dermatology and Nursing (IVDP), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

MeSH

AdultAnti-Inflammatory Agents, Non-SteroidalAntibodies, Monoclonal, HumanizedDrug SubstitutionEtanerceptFemaleHumansInterleukin-17MaleMiddle AgedPsoriasisSeverity of Illness IndexTreatment FailureTreatment Outcome

Pub Type(s)

Clinical Trial, Phase III
Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

28074446

Clinical Trial Links

Clinical trial which this article describes [1]
Clinical trial which this article describes [2]

Citation

Blauvelt, Andrew, et al. "Efficacy and Safety of Switching to Ixekizumab in Etanercept Non-Responders: a Subanalysis From Two Phase III Randomized Clinical Trials in Moderate-to-Severe Plaque Psoriasis (UNCOVER-2 and -3)." American Journal of Clinical Dermatology, vol. 18, no. 2, 2017, pp. 273-280.
Blauvelt A, Papp KA, Griffiths CEM, et al. Efficacy and Safety of Switching to Ixekizumab in Etanercept Non-Responders: A Subanalysis from Two Phase III Randomized Clinical Trials in Moderate-to-Severe Plaque Psoriasis (UNCOVER-2 and -3). Am J Clin Dermatol. 2017;18(2):273-280.
Blauvelt, A., Papp, K. A., Griffiths, C. E. M., Puig, L., Weisman, J., Dutronc, Y., Kerr, L. F., Ilo, D., Mallbris, L., & Augustin, M. (2017). Efficacy and Safety of Switching to Ixekizumab in Etanercept Non-Responders: A Subanalysis from Two Phase III Randomized Clinical Trials in Moderate-to-Severe Plaque Psoriasis (UNCOVER-2 and -3). American Journal of Clinical Dermatology, 18(2), 273-280. https://doi.org/10.1007/s40257-016-0246-9
Blauvelt A, et al. Efficacy and Safety of Switching to Ixekizumab in Etanercept Non-Responders: a Subanalysis From Two Phase III Randomized Clinical Trials in Moderate-to-Severe Plaque Psoriasis (UNCOVER-2 and -3). Am J Clin Dermatol. 2017;18(2):273-280. PubMed PMID: 28074446.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Efficacy and Safety of Switching to Ixekizumab in Etanercept Non-Responders: A Subanalysis from Two Phase III Randomized Clinical Trials in Moderate-to-Severe Plaque Psoriasis (UNCOVER-2 and -3). AU - Blauvelt,Andrew, AU - Papp,Kim A, AU - Griffiths,Christopher E M, AU - Puig,Luis, AU - Weisman,Jamie, AU - Dutronc,Yves, AU - Kerr,Lisa Farmer, AU - Ilo,Dapo, AU - Mallbris,Lotus, AU - Augustin,Matthias, PY - 2017/1/12/pubmed PY - 2017/5/13/medline PY - 2017/1/12/entrez SP - 273 EP - 280 JF - American journal of clinical dermatology JO - Am J Clin Dermatol VL - 18 IS - 2 N2 - BACKGROUND: Patients with psoriasis who have an inadequate response to one biologic may benefit from switching to a new biologic, such as ixekizumab, a high affinity monoclonal antibody that selectively targets interleukin (IL)-17A. OBJECTIVE: Our aim was to assess the response to ixekizumab in patients with moderate-to-severe plaque psoriasis who did not respond adequately to etanercept using a post-hoc analysis in two phase III studies. METHODS: For the subanalyses in two phase III trials (UNCOVER-2 and -3), non-response was defined by either failure to have a static physician global assessment (sPGA) of 0/1 in UNCOVER-2 or failure to have at least 75% improvement in psoriasis area and severity index (PASI 75) in UNCOVER-3 at Week 12 of each study. Non-responders treated with twice-weekly etanercept 50 mg in the first 12 weeks received two injections of placebo at Week 12 (4-week wash-out period), followed by ixekizumab every 4 weeks (Q4W) for Weeks 16-60. Non-responders to placebo in the first 12 weeks were administered ixekizumab 160 mg at Week 12, followed by ixekizumab Q4W for Weeks 16-60. RESULTS: After switching to ixekizumab Q4W, a substantial proportion of patients with moderate-to-severe psoriasis who did not respond to etanercept experienced rapid and durable improvement in all efficacy evaluations. Among sPGA 0/1 (UNCOVER-2) and PASI 75 (UNCOVER-3) non-responders to etanercept, 73.0% achieved sPGA 0/1 and 78.2% achieved PASI 75, respectively, after 12 weeks of ixekizumab treatment. Safety profiles in patients switched from etanercept to ixekizumab were similar to those in patients switched from placebo to ixekizumab. CONCLUSION: Patients who were non-responders to etanercept after 12 weeks, as defined by failure to meet sPGA 0/1 (UNCOVER-2) or PASI 75 (UNCOVER-3), achieved high levels of response 12 weeks after switching to ixekizumab. Studies are registered with ClinicalTrials.gov (NCT01597245 and NCT01646177). SN - 1179-1888 UR - https://www.unboundmedicine.com/medline/citation/28074446/Efficacy_and_Safety_of_Switching_to_Ixekizumab_in_Etanercept_Non_Responders:_A_Subanalysis_from_Two_Phase_III_Randomized_Clinical_Trials_in_Moderate_to_Severe_Plaque_Psoriasis__UNCOVER_2_and__3__ DB - PRIME DP - Unbound Medicine ER -
Grapherence [↓12 ↑13]

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