Taltz ® (ixekizumab) injektion

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Taltz® ▼ (ixekizumab): Entesis

Hos patienter med befintlig entesit resulterade behandling med ixekizumab Q4W förbättring av entesit vid vecka 24 jämfört med placebo.

Detailed Information

In SPIRIT-P1, compared with placebo, there were significantly more enthesitis responders (LEI=0) in the ixekizumab Q4W group at week 24 (p≤.001) and in the ixekizumab Q2W group at weeks 12 (p≤.01) and 24 (p≤.025).1

At week 24 in the SPIRIT-P2 trial, compared with placebo, the group of patients who received ixekizumab Q2W or Q4W had a numerically larger LEI response and a greater mean change from baseline in LEI.2

An integrated analysis of SPIRIT-P1 and SPIRIT-P2 demonstrated that significantly more patients treated with ixekizumab vs placebo had resolution of enthesitis at 24 weeks.3

The dosing schedule IXE Q2W mentioned in this statement is not consistent with the approved dosing schedule for psoriatic arthritis in the Taltz summary of product characteristics. Please refer to the Taltz summary of product characteristics for approved dosing.4

Description of Enthesitis Outcome Measures

Enthesitis is inflammation of the tendon, ligament, or joint capsule’s insertion sites into bone.5

Enthesitis was assessed by the LEI. The sites assessed by the LEI for presence or absence of tenderness were

  • lateral epicondyle (elbows), left and right

  • medial femoral condyle (knees), left and right, and

  • achilles tendon insertion, left and right.1,2

SPIRIT-P1 included an evaluation of the LEI for those patients with enthesitis at baseline as a secondary endpoint. A post hoc analysis was conducted for those patients with enthesitis and LEI>0 at baseline.1 SPIRIT-P2 included a pre-specified secondary endpoint of complete resolution of enthesitis in those patients with enthesitis and LEI>0 at baseline.2

Enthesitis Clinical Trial Results

Results Through Week 24

SPIRIT-P1

In SPIRIT-P1, 58% of all patients had baseline enthesitis.1

Compared with placebo, there were significantly more responders (LEI=0) in the ixekizumab Q4W group at week 24 (p≤.001) and in the ixekizumab Q2W group at weeks 12 (p≤.01) and 24 (p≤.025). The change from baseline in LEI score was significantly greater in the ixekizumab Q2W group than in the placebo group at week 12. There were no significant differences between adalimumab and placebo in LEI responders or change from baseline in LEI at weeks 12 or 24.1 See Table 1 for results.

Table 1. Improvement in Enthesitis in the SPIRIT-1 Trial at Weeks 12 and 241

 

PBO

IXE Q4W

IXE Q2W

ADA Q2W

Week 12

N=57

N=68

N=57

N=54

LEI=0, %

28.1

27.9

47.4a

35.2

LS mean change (SE) from baseline in LEI

-0.8 (0.24)

-0.9 (0.21)

-1.5 (0.24)a

-0.8 (0.24)

Week 24

N=57

N=70

N=59

N=56

LEI=0, %

19.3

42.6b

38.6c

33.3

LS mean change (SE) from baseline in LEI

-0.8 (0.26)

-1.3 (0.21)

-1.4 (0.24)

-0.9 (0.23)

Abbreviations: ADA = adalimumab; IXE = ixekizumab; LEI = Leeds Enthesitis Index; LS = least-squares; PBO = placebo; Q2W = every 2 weeks; Q4W = every 4 weeks.

a p≤.05 vs PBO.

b p≤.001 vs PBO.

c p≤.025 vs PBO.

SPIRIT-P2

In SPIRIT-P2, 61% of all patients had baseline enthesitis.2

At week 24 in the SPIRIT-P2 trial, compared with placebo, the group of patients who received ixekizumab Q4W or Q2W had a numerically larger LEI response response and a greater mean change from baseline in LEI.2 See Table 2 for results.

Table 2. Improvement in Enthesitis in the SPIRIT-P2 Trial at Week 242

 

PBO
(N=118)

IXE Q4W
(N=122)

IXE Q2W
(N=123)

LEI=0, %a

22

35

31

LS mean change (SE) from baseline in LEIa

-1.0 (0.4)

-1.1 (0.3)

-1.4 (0.3)

Abbreviations: IXE = ixekizumab; LEI = Leeds Enthesitis Index; LS = least-squares; PBO = placebo; Q2W = every 2 weeks; Q4W = every 4 weeks.

a Assessed in patients with baseline LEI>0.

Figure 1. Resolution of Enthesitis in SPIRIT-P2 Through Week 242

Abbreviations: LEI = Leeds Enthesitis Index; Q2W = 80 mg every 2 weeks; Q4W = 80 mg every 4 weeks.
* p<.05 vs placebo.

In a prespecified exploratory analysis, compared with placebo, a greater proportion of patients had resolution of enthesitis

  • at week 16 for the ixekizumab Q2W group (p=.0409)

  • at week 20 for the ixekizumab Q2W group (p=.0279), and

  • at week 20 for the ixekizumab Q4W group (p=.0321) (see Figure 1).2

Week 52 Results

SPIRIT-P1

Overall, in patients from the extension period population with LEI>0 at baseline in SPIRIT-P1, at week 52 complete resolution of enthesitis was achieved by

  • 51% of patients in the ixekizumab Q4W group, and

  • 43% of patients in the ixekizumab Q2W group.6

SPIRIT-P2

In the extension period population of SPIRIT-P2, of the patients with LEI>0 at baseline, at week 52 complete resolution of enthesitis was achieved by

  • 32/68 (47.1%) of patients in the ixekizumab Q4W/ixekizumab Q4W group, and

  • 30/84 (35.7%) of patients in the ixekizumab Q2W/ixekizumab Q2W group.7

Post hoc Integrated Analysis Results

The integrated analysis set of SPIRIT-P1 and SPIRIT-P2 was composed of 679 patients. Of these, 60% (n=403 of 675) had baseline enthesitis (LEI >0).5

Statistically significant differences between ixekizumab and placebo on rates of resolution of enthesitis (LEI=0; post hoc analysis) were observed in an integrated analysis based on all patients who had enthesitis at baseline (LEI >0) from the SPIRIT-P1 and SPIRIT-P2 integrated clinical trials (Figure 2).3

Furthermore, at entheseal points measured by the LEI, ixekizumab-treated patients had significantly higher resolution of enthesitis compared to placebo as shown in Figure 2.5

Figure 2. SPIRIT-P1 and SPIRIT-P2 Integrated Clinical Trial Dataset: LEI Resolution (LEI=0) at Different Entheseal Points at Week 24 in Patients With Enthesitis (LEI>0) at Baseline, NRI5

Abbreviations: IXE Q2W = ixekizumab 80 mg every 2 weeks following 160 mg starting dose; IXE Q4W = ixekizumab 80 mg every 4 weeks following 160 mg starting dose; LEI = Leeds Enthesitis Index; NRI = nonresponder imputation; PBO = placebo.
Notes: Achill tend insert = Achilles tendon insertion; Lat epicond = lateral epicondyle; Med fem cond = medial femoral condyle.
* p<.05 vs PBO.

Impact on Patient Reported Outcomes

The authors concluded that regardless of treatment

  • patients whose enthesitis resolved had two times the improvement in quality of life (EQ-5D VAS) compared to patients with residual enthesitis

  • pain also improved by more than 2-fold compared to patients who had residual enthesitis symptoms (as measured by pain VAS)

  • greater improvement in functional ability (HAQ-DI) was also seen in patients with resolution of enthesitis vs those with residual entheseal symptoms, and notably more than double the percentage of patients with resolution of enthesitis reported clinically meaningful changes in HAQ-DI compared to patients with unresolved enthesitis.5

Therapeutic Indication

Ixekizumab, alone or in combination with methotrexate, is indicated for the treatment of active psoriatic arthritis in adult patients who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drug (DMARD) therapies.4

References

1. 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

2. 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

3. Combe B, Nash P, Adams D, et al. Integrated efficacy and safety results from SPIRIT-P1 and SPIRIT-P2, two phase 3 trials of ixekizumab for the treatment of psoriatic arthritis. Poster presented at: 26th Congress of the European Academy of Dermatology and Venereology (EADV); September 13-17, 2017; Geneva, Switzerland.

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

5. Gladman DD, Orbai AM, Klitz U, et al. Ixekizumab and complete resolution of enthesitis and dactylitis: integrated analysis of two phase 3 randomized trials in psoriatic arthritis. Arthritis Res Ther. 2019;21(1):38. http://dx.doi.org/10.1186/s13075-019-1831-0

6. Mease PJ, Okada M, Kishimoto M, et al. Efficacy and safety of ixekizumab in patients with active psoriatic arthritis: 52-week results from a phase 3 study (SPIRIT P1). Abstract presented at: European League Against Rheumatism (EULAR) Congress; June 8-11, 2016; London, England.

7. Genovese MC, Combe B, Kremer JM, et al. Safety and efficacy of ixekizumab in patients with PsA and previous inadequate response to TNF inhibitors: week 52 results from SPIRIT-P2. Rheumatology. 2018;57(11):2001-2011. http://dx.doi.org/10.1093/rheumatology/key182

Glossary

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

bDMARD = biologic disease-modifying antirheumatic drug

EQ-5D VAS = European Quality of Life - 5 Dimensions Visual Analog Scale

HAQ-DI = Health Assessment Questionnaire-Disability Index

LEI = Leeds Enthesitis Index

PsA = psoriatic arthritis

Q2W = every 2 weeks

Q4W = every 4 weeks

TNF = tumor necrosis factor

VAS = Visual Analog Scale

This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.

Datum fӧr senaste ӧversyn 2019 M04 24


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