Taltz ® (ixekizumab) injektion

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Taltz® ▼ (ixekizumab): Utformning av pivotala prövningar för psoriasisartrit

Ixekizumab har undersökts i tre pivotala kliniska fas 3-prövningar för aktiv psoriasisartrit.

Summary

Information included in this response may not completely match the current labeling for Ixekizumab. Please refer to the Taltz Summary of Product Characteristics for approved dosing.1

  • Two multicenter, randomized, double-blind, placebo-controlled studies (SPIRIT-P1 and SPIRIT-P2) and one trial with a 36-week open-label period followed by a randomized, double-blind withdrawal period (SPIRIT-P3) enrolled a total of 1350 patients 18 years of age and older with active PsA.

    • SPIRIT-P1 (N=417) is a phase 3, 24-week double-blind, placebo-controlled trial with an active reference arm in patients with active PsA who are naïve to bDMARDs with an extension period of up to 3 years.2

    • SPIRIT-P2 (N=363) is a phase 3, 24-week double-blind, placebo-controlled trial in patients with active PsA and an inadequate response or intolerance to TNF inhibitor, with an extension period of up to 3 years.3

    • SPIRIT-P3 (N=570) consists of a 36-week open-label period followed by a randomized double-blind withdrawal period from week 36 to week 104. This trial is being conducted in patients naïve to bDMARDs.4,5

  • In SPIRIT-P1 and SPIRIT-P2, the primary endpoint was the proportion of patients who achieved an ACR20 response at week 24, which represents a 20% improvement in joint symptoms.2,3 The 24-week double-blind treatment period in both studies was followed by an extension period (up to week 52 for SPIRIT-P1 and up to week 156 for SPIRIT-P2), and a long-term extension period for up to 3 years in SPIRIT-P1 (both trials lasted a total of 3 years).2,6

  • The primary outcome of SPIRIT-P3 is the time to relapse, defined as no longer meeting MDA, during the double-blind withdrawal period. One of the secondary outcomes of SPIRIT-P3 is the time to regain MDA after retreatment with ixekizumab in patients who relapsed.4

Study Design

The study design of the 3 clinical trials of ixekizumab in patients with PsA are illustrated in Figure 1, Figure 2, and Figure 3.

Figure 1. SPIRIT-P1 Study Design Including Extension Period up to Week 1566

Abbreviations: ADA = 40 mg adalimumab every 2 weeks; IR = inadequate responder (imputed as nonresponder); IXE = ixekizumab; PBO = placebo; Q2W = every 2 weeks; Q4W = every 4 weeks; R = randomization; RT = rescue therapy; SJC = swollen joint count; TJC = tender joint count.

Notes:
All patients randomized to IXE received a 160 mg starting dose (as 2 injections) followed by 80 mg Q2W or Q4W; criteria for defining IRs were blinded to investigators. Adalimumab was an active reference arm.

Inadequate responders to PBO at week 16 were randomized to IXE Q2W or IXE Q4W. Inadequate responders to ADA at week 16 were rerandomized to IXE Q2W or IXE Q4W and underwent an 8-week PBO washout period prior to receiving IXE at week 24.

Inadequate responders continued on designated therapy and received rescue therapy.
b
 Inadequate responders in IXE arms at week 16 maintained IXE dose but were required to change background (concomitant) therapy.
c
Active reference arm.
d
Concomitant medication could be added, modified, or withdrawn at any time after week 24.
e
Patients failing to demonstrate ≥20% improvement in both TJC and SJC at week 32, or any subsequent visit, were discontinued from the study.

Figure 2. SPIRIT-P2 Study Design Including Extension Period7

Abbreviations: IXE = ixekizumab; IXE Q2W= ixekizumab 80 mg every 2 weeks; IXE Q4W = ixekizumab 80 mg ixekizumab every 4 weeks; PBO = placebo; RT = rescue therapy; SJC = swollen joint count; TJC= tender joint count.

a Plus RT in inadequate responders.
b
Patients were discontinued from the study if they did not demonstrate at least a 20% improvement from baseline in both TJC and SJC at week 32 or at any subsequent visit during the study.
Note: All IXE patients (starting IXE at weeks 0, 16, or 24) received a 160 mg starting dose (as 2 injections) followed by 80 mg IXE Q2W or IXE Q4W; criteria for defining inadequate responders were blinded to investigators.

Figure 3. SPIRIT-P3 Clinical Study Design5

Abbreviations: IXE Q2W = ixekizumab every 2 weeks; MDA = minimal disease activity; PBO = placebo; SJC = swollen joint count; TJC = tender joint count.

Patients were discontinued if they failed to demonstrate ≥20% improvement in TJC and SJC at week 24 or at any subsequent visit through week 104, except from the point of randomization until the visit after relapse for patients randomized in the double-blind withdrawal period.
b
Between weeks 36 and 64, patients who achieved MDA criteria for ≥4 visits over 3 consecutive months were randomized 1:1:1 to IXE Q2W or IXE Q2W withdrawal. Patients randomized to IXE Q2W withdrawal received PBO.
Patients not meeting randomization criteria by week 64 continued on IXE Q2W until week 104.
d
Patients who relapsed by no longer meeting MDA criteria received IXE Q2W until week 104.

References

1. Taltz [summary of product characteristics]. Eli Lilly Nederland B.V., The Netherlands.

2. Mease PJ, van der Heijde D, Ritchlin CT, et al. Ixekizumab, an interleukin-17A specific monoclonal antibody, for the treatment of biologic-naive patients with active psoriatic arthritis: results from the 24-week randomised, double-blind, placebo-controlled and active (adalimumab)-controlled period of the phase III trial SPIRIT-P1. Ann Rheum Dis. 2017;76(1):79-87. http://dx.doi.org/10.1136/annrheumdis-2016-209709

3. Nash P, Kirkham B, Okada M, et al. Ixekizumab for the treatment of patients with active psoriatic arthritis and an inadequate response to tumour necrosis factor inhibitors: results from the 24-week randomized, double-blind, placebo-controlled period of the SPIRIT-P2 phase 3 trial. Lancet. 2017;389(10086):2317-2327. http://dx.doi.org/10.1016/S0140-6736(17)31429-0

4. A long-term efficacy and safety study of ixekizumab (LY2439821) in participants with active psoriatic arthritis (SPIRIT P3). ClinicalTrials.gov identifier: NCT02584855. Updated November 15, 2019. Accessed June 18, 2020. https://www.clinicaltrials.gov/ct2/show/NCT02584855?term=SPIRIT-P3&rank=1.

5. Coates LC, Pillai SG, Zhang L, et al. Continuing versus withdrawing ixekizumab in patients with psoriatic arthritis who achieved sustained minimal disease activity: results from the SPIRIT-P3 study. Poster presented at: Annual Meeting of the American College of Rheumatology; November 8-13, 2019; Atlanta, Georgia.

6. Chandran V, Fleischmann R, Lespessailles E, et al. Efficacy and safety of ixekizumab in patients with active psoriatic arthritis: three year results from a phase 3 study (SPIRIT-P1). Poster presented at: 2018 Meeting of the European League Against Rheumatism (EULAR); June 13-16, 2018; Amsterdam, Netherlands.

7. Data on file, Eli Lilly and Company and/or one of its subsidiaries.

Glossary

ACR20 = 20% improvement from baseline in American College of Rheumatology Index

bDMARD = biologic disease-modifying antirheumatic drug

MDA = minimal disease activity

PsA = psoriatic arthritis

TNF = tumor necrosis factor

Datum fӧr senaste ӧversyn 2020 M06 15


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