Taltz ® (ixekizumab) injektion

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Taltz® ▼ (ixekizumab): Långsiktig säkerhet vid plackpsoriasis

Exponeringsjusterad incidens för behandlingsrelaterade biverkningar och allvarliga biverkningar förblev stabila eller minskade över tiden i ixekizumab kliniska studier.

General Information

  • The long-term safety of ixekizumab has been evaluated in 6091 patients with PsO who received ixekizumab up to 5 years (17,499.3 PYs). The safety profile is consistent with previous reports in patients who received ixekizumab for the treatment of PsO and the rates of reported AEs remained stable or decreased over time with continued ixekizumab exposure.1

  • Note that data from multiple, different dosing regimens, including unapproved doses, are included in this response.

  • Comparisons between treatment periods described for the phase 3 UNCOVER trials summarized in this response are descriptive in nature, and not statistical comparisons.

  • Brief descriptions of the pivotal clinical trials for moderate-to-severe plaque PsO are provided at the end of this response (see  ).

Phase 3 Clinical Trials

In an integrated analysis of safety data from 3 pivotal phase 3 clinical trials which had an induction period of 12 weeks, 2 of which were followed by a randomized withdrawal maintenance period of 48 additional weeks, the EAIR per 100 PYs for TEAEs and SAEs remained stable or decreased over time through week 60 (see Table 1).2

Across the 12-week induction periods of UNCOVER-1, -2, and -3, the 48-week maintenance periods of UNCOVER-1 and -2, and the long-term extension period to week 60 of UNCOVER-3, most TEAEs were mild or moderate in severity and generally did not lead to treatment discontinuation.3-5 In all 3 trials, long-term safety will continue to be evaluated for up to a total of 5 years in patients who participate through the entire studies.4

Table 1. Incidence Rates of Treatment-Emergent Adverse Events and Serious Adverse Events Through Week 60 in Phase 3 UNCOVER Clinical Trials2,6

Event

12-Week Induction Period From UNCOVER-1, UNCOVER-2, and UNCOVER-3

48-Week Maintenance Period From UNCOVER-1 and UNCOVER-2

Placebo
(N=791; 180 PYs)

IXE Q2W
(N=1167; 269 PYs)

IXE Q4W
(N=1161; 266 PYs)

Placebo
(N=402; 188 PYs)

IXE Q4W
(N=416; 345 PYs)

IXE Q12W
(N=408; 282 PYs)

Any TEAE, IRa

205.5

253.6b

256.8b

123.8

95.6b

106.2

Any SAE, IRa

6.7

7.4

9.8

8.0

7.5

8.1

Abbreviations: IR = exposure-adjusted incidence rate per 100 patient-years; IXE = ixekizumab; PY = patient-years; Q2W = every 2 weeks; Q4W = every 4 weeks; Q12W = every 12 weeks; SAE = serious adverse event; TEAE =-treatment-emergent adverse event.

a IRs were calculated by dividing the total number of patients experiencing the TEAE by the sum of all patients’ time (in 100 years) of exposure during the treatment period.

b p<.05 vs placebo.

UNCOVER-3 Open-Label Long-Term Extension Data 

A 204-week follow up on patients from the UNCOVER-3 study includes safety data on TEAEs, SAEs, deaths, and discontinuations due to AEs (see  ).7

Table 2. Treatment-Emergent Adverse Events, Serious Adverse Events, Deaths, and Discontinuations From the 204-Week UNCOVER-3 Open-Label Long-Term Extension7

Event

PBO/IXE Q4W
(N=183)
n (%)

ETN/IXE Q4W 
(N=369)
n (%)

IXE Q4W
(N=360)
n (%)

IXE Q2W/Q4W
(N=362)
n (%)

Total LTE Population
(N=1274)

Patients with ≥1 TEAE

163 (89.1)

328 (88.9)

316 (87.8)

322 (89.0)

1129 (88.6)

Patients with ≥1 SAE

44 (24.0)

69 (18.7)

70 (19.4)

47 (13.0)

230 (18.1)

Deaths

2 (1.1)

3 (0.8)

1 (0.3)

2 (0.6)

8 (0.6)

Discontinuation due to AE

17 (9.3)

34 (9.2)

37 (10.3)

32 (8.8)

120 (9.4)

Abbreviations: AE = adverse event; ETN/IXE Q4W = etanercept 50 mg twice weekly for 12 weeks followed by 4-week washout, then ixekizumab 80 mg every 4 weeks; IXE Q2W/IXE Q4W = ixekizumab 80 mg every 2 weeks for 12 weeks, then every 4 weeks; IXE Q4W = ixekizumab every 4 weeks; LTE = long-term extension period; PBO/IXE Q4W = placebo for 12 weeks, then ixekizumab every 4 weeks; SAE = serious adverse event; TEAE = treatment-emergent adverse event.
Notes: Patients may be counted in more than one category. Patients with multiple occurrences of the same event are categorized by the highest severity.

Integrated Analysis of Ixekizumab Exposures

In 14 completed and ongoing ixekizumab clinical trials for psoriasis, 6091 patients with PsO have received at least 1 dose of ixekizumab, representing 17,499.3 PYs of exposure as of the data cutoff of March 21, 2019.1

The numbers of TEAEs, SAEs, deaths, and discontinuations due to an AE as of March 21, 2019 are shown in Table 3.

The numbers of AEs of special interest as of March 21, 2019 are shown in Table 4.

Table 3. Treatment-Emergent Adverse Events and Serious Adverse Events in All Treatment Periods in All Psoriasis Ixekizumab Exposures Integrated Analysis Set1

Event, n (%) [IR]a

Pooled IXE
(N=6091; 17,499.3 PYs)
b

Patients with ≥1 TEAE

5259 (86.3) [30.1]c

Patients with ≥1 SAE

942 (15.5) [5.4]

Deaths

35 (0.6) [0.2]

Discontinuation due to AE

490 (8.0) [2.8]

Abbreviations: AE = adverse event; IR = incidence rate; IXE = ixekizumab; PY = patient year; SAE = serious adverse event; TEAE = treatment-emergent adverse event.
Notes: Patients may be counted in more than one category. Patients with multiple occurrences of the same event are categorized by the highest severity. Deaths are included among SAEs and among discontinuations due to AEs.

a IR per 100 PYs.

b Data through March 21, 2019.

c The most commonly reported TEAEs (IR per 100 PYs) were nasopharyngitis (8.8), upper respiratory tract infection (unspecified: 5.4), and injection site reaction (3.4).

Table 4. Adverse Events of Special Interest in All Treatment Periods in All Psoriasis Ixekizumab Exposures Integrated Analysis Set1

Event, n (%) [IR]a

Pooled IXE
(N=6091; 17,499.3 PYs)
b

Infections

3976 (65.3) [22.7]

Serious infections

227 (3.7) [1.3]

Oral candidiasis

140 (2.3) [0.8]

Injection site reactions

928 (15.2) [5.3]

Inflammatory bowel disease (unadjudicated)

29 (0.5) [0.2)c

MACE (adjudicated)

85 (1.5) [0.5]

Malignancies

134 (2.2) [0.8]

Depression

209 (3.4) [1.2]d

Abbreviations: IR = incidence rate; IXE = ixekizumab; MACE = major adverse cerebro-cardiovascular events; PY = patient year.

a The IR per 100 PYs considered exposure time as the entire time on ixekizumab.

b Data through 21 March 2019.

c The IR of adjudicated inflammatory bowel disease was 0.2.

d The rate of suicide ideation or behavior was 0.1. There were no completed suicides in the psoriasis clinical studies.

Please find the full list of adverse drug reactions of ixekizumab in the Taltz summary of product characterstics.8

The rates of TEAEs including SAEs remained stable or decreased over time with continued exposure to ixekizumab up to 5 years (see Figure 1).1

Figure 1. Incidence Rates of Select Categories of Adverse Events at 1-year Intervals Up to 5 Years of Treatment in Patients Exposed to Ixekizumab in the Psoriasis Clinical Development Program1

Abbreviations: IBD = inflammatory bowel disease; IR = incidence rate; IXE = ixekizumab; MACE = major adverse cerebro-cardiovascular events; PBO = placebo; PY = patient years; SAE = serious adverse events.

a Data are IR for 0-12 weeks for the induction-dosing period for UNCOVER-1, -2, and -3 only.

Therapeutic Indication

Ixekizumab is indicated for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy.8

References

1. Genovese MC, Kameda H, Rahman P, et al. Safety profile of ixekizumab in patients with moderate-to-severe plaque psoriasis and psoriatic arthritis: integrated analysis of 18 clinical trials. Poster presented at: American College of Rheumatology/ARP; November 8-13, 2019; Atlanta, GA.

2. Strober B, Papp KA, Leonardi C, et al. Integrated safety of ixekizumab in patients with moderate-to-severe psoriasis: results from a pooled analysis of 7 clinical trials. Poster presented at: 74th Annual Meeting of the American Academy of Dermatology; March 4-8, 2016; Washington, DC.

3. Blauvelt A, Papp KA, Langley R, et al. Efficacy and safety of continuous ixekizumab treatment for 60 weeks in moderate-to-severe plaque psoriasis: Results from the UNCOVER-3 trial. Poster presented at: 74th Annual Meeting of the American Academy of Dermatology, March 4-8, 2016; Washington, DC

4. 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

5. 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

6. Strober B, Leonardi C, Papp KA, et al. Short- and long-term safety outcomes with ixekizumab from 7 clinical trials in psoriasis: etanercept comparisons and integrated data. J Am Acad Dermatol. 2017;76(3):432-440 e417. http://www.sciencedirect.com/science/article/pii/S0190962216308684

7. Lebwohl MG, Gordon KB, Gallo G, et al. Ixekizumab sustains high level of efficacy and favorable safety profile over 4 years in patients with moderate psoriasis: results from UNCOVER-3 study. 2020;34(2):301-309. J Eur Acad Dermatol Venereol. http://dx.doi.org/10.1111/jdv.15921

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

Glossary

AE = adverse event

EAIR = exposure adjusted incidence rate

PsO = psoriasis

PY = patient-years

SAE = serious adverse event

TEAE = treatment-emergent adverse event

Appendix: Clinical Trial Brief Descriptions 

  • UNCOVER-1, -2, and -3 (N=3866) phase 3 trials in moderate-to-severe plaque psoriasis were integrated to evaluate the safety of ixekizumab in comparison to placebo up to 12 weeks after treatment initiation.

  • The phase 3 trials examined the efficacy and safety of ixekizumab compared with placebo and etanercept (UNCOVER-2 and -3) during induction treatment and vs placebo in maintenance (UNCOVER-1 and -2).4

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 M10 25


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