Taltz ® (ixekizumab) injektion

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Taltz® (ixekizumab): Plackpsoriasis - Effekt på klåda

Ixekizumab-behandlade patienter rapporterade signifikanta förbättringar av klådans svårighetsgrad jämfört med placebo under induktions- och underhållsbehandling.

Impact of Ixekizumab on Itch

The impact of ixekizumab on change in itch severity from baseline was assessed using the itch NRS scale as a secondary endpoint in the pivotal UNCOVER phase 3 clinical studies. The itch NRS rating scale is an 11-point scale ranging from 0, meaning “no itching”, to 10, meaning “worst itch imaginable”, in which patients report itch severity in the past 24 hours.1

Induction Period Results

As shown in Figure 1, itch NRS scores were statistically significantly different in the ixekizumab Q2W and Q4W treatment arms compared to placebo during the induction period (weeks 0-12) of UNCOVER-2. Ixekizumab-treated patients in UNCOVER-1 and UNCOVER-3 also had statistically significant improvements in itch severity compared to placebo-treated patients as early as week 1 and at each assessment through week 12.1

Figure 1. UNCOVER-2: Mean Itch NRS Score Through Week 121

Abbreviations: ETN = etanercept; IXE Q2W = ixekizumab 80 mg every 2 weeks; IXE Q4W = ixekizumab 80 mg every 4 weeks; NRS = numeric rating scale; PBO = placebo.

* p<.001 vs PBO.

In all 3 pivotal UNCOVER clinical trials, patients treated with ixekizumab experienced significant improvement in itch severity when compared to placebo (or etanercept in UNCOVER-2 and -3) at week 12.1,2 Additionally, significantly more patients in the ixekizumab treatment groups than patients in placebo or etanercept treatment groups achieved the minimal clinically important difference for itch, which was defined as a ≥4-point reduction in itch NRS from baseline (see Table 1 below).1 

Table 1.  Itch NRS Change From Baseline to Week 12 in UNCOVER-1, -2, and 3 2-4

Clinical Trial
Treatment Arm

Baseline itch NRS, mean (SD)

Itch NRS change from baseline, LSMa

4-Point Reduction in Itch NRS, % Patientsb

UNCOVER-1

PBO

7 (3)

-0.3

15.5

IXE Q4W

7 (3)

-5.4c

80.5c

IXE Q2W

7 (2)

-5.6c

85.9c

UNCOVER-2

PBO

6 (3)

-0.4

14.1

ETN

7 (3)

-3.6d

57.8d

IXE Q4W

7 (3)

-4.9de

76.8de

IXE Q2W

7 (3)

-5.2de

85.1de

UNCOVER-3

PBO

7 (3)

-0.6

20.9

ETN

6 (3)

-3.9d

64.1d

IXE Q4W

6 (3)

-4.9de

79.9de

IXE Q2W

6 (3)

-5.1de

82.5de

Abbreviations: ETN = etanercept; IXE Q2W = ixekizumab 80 mg every 2 weeks; IXE Q4W = ixekizumab 80 mg every 4 weeks; LSM = least squares mean; MMRM = mixed-effects model for repeated measures; NRI = nonresponder imputation; NRS = numeric rating scale; PBO = placebo.

a MMRM.

b NRI, among patients with itch NRS ≥4 at baseline.

c p<.001 vs PBO.

d p<.0001 vs PBO.

e p<.0001 vs ETN

Maintenance Period Results

In all 3 pivotal UNCOVER clinical trials, continuous treatment with ixekizumab Q4W in the maintenance period sustained the week 12 Itch NRS responses through week 60, represented in Figure 2.5-7 Additionally, the percentage of patients randomized to ixekizumab Q4W during the maintenance period of UNCOVER-1 who maintained an itch NRS score of 0 was similar between week 12 (52.4%) and week 60 (50.2%).5 Additional details regarding study design can be found in  .

Figure 2. UNCOVER-2: Itch NRS Change From Baseline, LSM, LOCF6

Abbreviations: IXE = ixekizumab; IXE Q4W = ixekizumab 80 mg every 4 weeks; IXE Q12W = ixekizumab 80 mg every 12 weeks; LSM = least squares mean; LOCF = last observation carried forward; NRS = numeric rating scale; PBO = placebo; sPGA = static Physician Global Assessment.

aWeek 12 sPGA (0,1) responders.

 p<.01 vs. IXE/PBO.

 *p<.001 vs. IXE/PBO.

Long-Term Extension Period Results

Figure 3 depicts complete itch resolution, defined as itch NRS=0, and ≥4-point improvement in itch response rates through week 264 in an integrated analysis from UNCOVER-1 and -2. The authors concluded ixekizumab provided clinically meaningful improvements in itch that were maintained through 5 years of continuous treatment.8

Figure 3. Integrated UNCOVER-1 and -2: Itch NRS Response Rates Through Week 2648

Abbreviations: IXE = ixekizumab; mNRI = modified nonresponder imputation; NRS = numeric rating scale; Nx = number of patients with nonmissing data.

a Analysis based on patients with itch NRS ≥4 at baseline.

Baseline Itch Severity Results

To evaluate the impact of baseline itch severity on the efficacy of ixekizumab treatment, a post hoc analysis of integrated UNCOVER-2 and -3 data was performed. At week 12, the percentage of ixekizumab treated patients achieving the minimal clinically important difference for itch (≥4-point reduction in itch NRS from baseline) was 

  • 70.0% with baseline itch NRS 4-6

  • 88.6% with baseline itch NRS 7-8, and

  • 90.8% for baseline itch NRS 9-10 (p<.001 vs etanercept and placebo for all severity subgroups).9

Long-term impact of the baseline itch severity subgroups was evaluated in UNCOVER-3, where all patients received ixekizumab Q4W after week 12. As shown in Figure 4, through 156 weeks of ixekizumab treatment, the percentage of patients achieving the clinically meaningful improvement in itch was consistent; however, fewer patients in the baseline itch NRS 4-6 subgroup achieved ≥4-point reduction in itch NRS from baseline compared to those with baseline itch NRS 7-8 and baseline itch NRS 9-10.9

Figure 4. UNCOVER-3: Itch NRS Reduction ≥4 by Baseline Itch Severity Subgroups Through Week 156, MI9

Abbreviations: MI = multiple imputation; NRS = numeric rating scale.

Therapeutic Indications

Ixekizumab is indicated for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy.10

References

1. Kimball AB, Luger T, Gottlieb A, et al. Impact of ixekizumab on psoriasis itch severity and other psoriasis symptoms: results from 3 phase III clinical trials. J Am Acad Dermatol. 2016;75(6):1156-1161. http://dx.doi.org/10.1016/j.jaad.2016.07.034

2. Griffiths CEM, 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(9993):541-551. http://dx.doi.org/10.1016/S0140-6736(15)60125-8

3. Kimball AB, Kaufmann R, Nikai E, et al. Impact of ixekizumab on psoriasis itch severity and other outcomes: results from the UNCOVER-1 trial. Poster presented at: 24th Congress of the European Academy of Dermatology and Venereology; October 7-11, 2015; Copenhagen, Denmark.

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

5. Kimball AB, Luger T, Gottlieb A, et al. Treatment with ixekizumab over 60 weeks provides sustained improvements in itch and other patient-reported outcomes: results from UNCOVER-1, a phase 3 trial. Poster presented at: 74th Annual Meeting of the American Academy of Dermatology; March 4-8, 2016; Washington, D.C.

6. Strober B, Sofen H, Bachelez H, et al. Continued treatment with ixekizumab over 60 weeks provides sustained improvements in itch and other patient reported outcomes: results from UNCOVER-2, a phase 3 trial. Poster presented at: 5th International Congress on Psoriasis; July 7-9, 2016; Paris, France.

7. Kimball AB, Luger T, Gottlieb A, et al. Long-term impact of ixekizumab on psoriasis itch severity: results from a phase III clinical trial and long-term extension. Acta Derm Venereol. 2018;98(1):98-102. http://dx.doi.org/10.2340/00015555-2801

8. Gooderham M, Iversen L, Torri H, et al. Ixekizumab-treated patients with moderate-to-severe plaque psoriasis maintained improvements in patient-reported outcomes over 5 years: results from 2 phase 3 clinical trials. Poster presented at: 29th Annual Meeting of the European Academy of Dermatology and Venereology (EADVirtual); October 29-31, 2020.

9. Yosipovitch G, Reich A, Steinhoff M, et al. Impact of ixekizumab treatment on itch and psoriasis area and severity index in patients with moderate-to-severe plaque psoriasis: an integrated analysis of two phase III randomized studies. Dermatol Ther (Heidelb). 2018;8(4):621-637. http://dx.doi.org/10.1007/s13555-018-0267-9

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

11. 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(4):345-356. http://dx.doi.org/10.1056/NEJMoa1512711

Glossary

NRS = numeric rating scale

Q2W = every 2 weeks

Q4W = every 4 weeks

Appendix A: Clinical Trials Brief Description

Figure 5. Induction (UNCOVER-1, -2, -3) and Maintenance (UNCOVER-1, -2) Dosing Period Study Designs11

Abbreviations: ETN = etanercept; IXE Q2W = ixekizumab 80 mg every 2 weeks; IXE Q4W = ixekizumab 80 mg every 4 weeks; IXE Q12W = ixekizumab 80 mg every 12 weeks; PBO = placebo; R = randomization; sPGA = static Physician Global Assessment.

Notes:
ETN arm was not included in UNCOVER-1.

Responders (sPGA 0 or 1) to ixekizumab at week 12 were rerandomized to receive IXE Q4W, IXE Q12W, or PBO.

Non-responders to ETN at week 12 in UNCOVER-2 were switched to IXE Q4W (without a 160 mg starting dose) after a 4-week washout period.

Non-responders to PBO at week 12 received a 160 mg starting dose of ixekizumab followed by IXE Q4W.

(dotted line) = relapse (sPGA≥3).

UNCOVER-3 is not represented in maintenance period design as the extension period consisted of open-label treatment with IXE Q4W.

Datum fӧr senaste ӧversyn 2020 M10 16


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