Taltz ® (ixekizumab) injektion

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Taltz (ixekizumab): Infektioner

Övre luftvägsinfektioner, oral candidiasis, konjunktivit och tinea infektioner förekom oftare med ixekizumab än med placebo.

Ixekizumab Label Information Related to Infections

General Information

Ixekizumab is contraindicated in patients with clinically important active infections (e.g. active tuberculosis).1

Treatment with ixekizumab is associated with an increased rate of infections such as

  • upper respiratory tract infection,

  • oral candidiasis,

  • conjunctivitis, and

  • tinea infections.1

Ixekizumab should be used with caution in patients with clinically important chronic infection or a history of recurrent infection. Patients should be instructed to seek medical advice if signs or symptoms suggestive of an infection occur.

  • If an infection develops, monitor carefully and discontinue ixekizumab if the patient is not responding to standard therapy or the infection becomes serious.

  • Ixekizumab should not be resumed until the infection resolves.1

Ixekizumab must not be given to patients with active tuberculosis (TB).

  • Consider anti-TB therapy prior to initiation of ixekizumab in patients with latent TB.1

Detailed Description

In the placebo-controlled period of the phase III clinical studies in plaque psoriasis in adults, infections were reported in

  • 27.2% of patients treated with ixekizumab for up to 12 weeks compared with

  • 22.9% of patients treated with placebo.1

The majority of infections were non-serious and mild to moderate in severity, most of which did not necessitate treatment discontinuation.

Serious infections occurred in

  • 13 (0.6%) of patients treated with ixekizumab and in

  • 3 (0.4%) of patients treated with placebo.

Over the entire treatment period infections were reported in 52.8% of patients treated with ixekizumab (46.9 per 100 patient years).

Serious infections were reported in 1.6% of patients treated with ixekizumab (1.5 per 100 patient years). 1

Infection rates observed in psoriatic arthritis and axial spondyloarthritis clinical studies were similar to those observed in the plaque psoriasis studies with the exception of the frequencies of the adverse reactions of

  • influenza and

  • conjunctivitis

which were common in patients with psoriatic arthritis.1

Please refer to the Taltz summary of product characteristics for the full list of adverse drug reactions.1

Psoriasis Clinical Trials

Induction Period

Across the 12-week primary psoriasis placebo-controlled integrated analysis (UNCOVER-1, -2, and -3),

  • most treatment-emergent infections were mild or moderate in severity, did not lead to treatment discontinuations, and were of 1 to 2 weeks duration

  • specific infection rates were overall comparable across treatment groups

  • serious infection incidence rates were low and similar across treatment groups, and 

  • in patients treated with ixekizumab during this period, there were no reports of

    • clinically active or reactivated TB

    • herpes zoster, or

    • invasive fungal infections.2

Integrated Safety Data

An integrated safety analysis was conducted from all ixekizumab adult and pediatric psoriasis exposures (N=6645; PY=17,902.0) across 15 adult and 1 pediatric plaque psoriasis clinical trials as of March 19, 2020. The proportion of patients with

  • any infection was 63.0% [IR=23.4 per 100 PYs of exposure]

  • serious infection was 3.4% [IR=1.3 per 100 PYs of exposure]

  • all Candida infections was 5.0% [IR=1.9 per 100 PYs of exposure], and 

  • potential opportunistic infections was 8.0% [IR=3.0 per 100 PYs of exposure].3

The IR of infections did not increase with longer ixekizumab exposure, up to 5 years.3

Psoriatic Arthritis Clinical Trials

24-Week Double-Blinded Treatment Period

In the 24-week, double-blind treatment periods of SPIRIT-P1 and SPIRIT-P2,

  • a similar increase in risk of infection was seen in previous placebo-controlled trials in plaque psoriasis

  • the most commonly reported infections in both trials were nasopharyngitis and upper respiratory tract infection

  • most infections were reported as mild-to-moderate in severity

  • no cases of invasive fungal disease were reported in either trial, and 

  • no cases of active or reactivated TB were reported in either trial.4,5

Integrated Safety Data

An integrated safety analysis was conducted from all ixekizumab psoriatic arthritis exposures (N=1401; PY=2247.7) across 4 psoriatic arthritis clinical trials as of March 19, 2020. The proportion of patients with 

  • any infection was 54.2% [IR=33.8 per 100 PYs of exposure]

  • serious infection was 2.0% [IR=1.2 per 100 PYs of exposure]

  • all Candida infections was 3.2% [IR=2.0 per 100 PYs of exposure], and 

  • opportunistic infections (including oral candidiasis, invasive candidiasis, herpes zoster, and hepatitis B reactivation) was 2.9% [1.8 per 100 PYs of exposure].6

The IR of infections decreased over time.7

Axial Spondyloarthritis Clinical Trials

In clinical trials in patients with axSpA (including AS/r-axSpA and nr-axSpA), infections reported in patients treated with ixekizumab 80 mg Q4W include

  • upper respiratory tract infection, including nasopharyngitis, pharyngitis, and upper respiratory tract infection (very common; reported at a ≥10% frequency)

  • tinea infection (uncommon; reported at a frequency ≥0.1% and <1%)

  • influenza (uncommon; reported at a frequency ≥0.1% and <1%)

  • conjunctivitis (uncommon; reported at a frequency ≥0.1% and <1%), and

  • rhinitis (uncommon; reported at a <1% frequency).6

16-week Double-Blinded Treatment Period of AS/r-axSpA Trials

In the 16-week double-blinded treatment periods of COAST-V and COAST-W,

  • the frequency of treatment-emergent infections was higher in the ixekizumab treatment groups vs placebo group

  • most infections were mild-to-moderate in severity, and

  • five infection-related SAEs were reported, and none led to study discontinuation.8,9

52-week Double-Blinded Treatment Period of nr-axSpA Trial

In COAST-X, most infections were mild-to-moderate in severity, and the most common infections were nasopharyngitis and upper respiratory tract infection (Table 1).6,10

Table 1. Summary of Infections From the COAST-X Safety Populationa During the 52-Week Double-Blind Treatment Period of COAST-X6,10


PBO
N=104

IXE Q4W
N=96

IXE Q2W
N=102

Infections, n (%)

30 (29)

38 (40)

43 (42)

Mild

24 (23)

20 (21)

29 (28)

Moderate 

6 (6)

17 (18)

13 (13)

Severe

0 (1)

1 (1)

1 (1)

Most common infections




Nasopharyngitis

8 (8)

18 (19)

16 (16)

URTI

4 (4)

4 (4)

6 (6)

Discontinuation due to infection

0

0

0

Serious infections

0

1 (1)b

0

Opportunistic infections

Oral candidiasis

1 (1)

0

0

Herpes zoster

1 (1)

2 (2)

0

Reactivated TB

0

0

0

Abbreviations: IXE Q2W = ixekizumab 80 mg every 2 weeks; IXE Q4W = ixekizumab 80 mg every 4 weeks; PBO = placebo; TB = tuberculosis; URTI = upper respiratory tract infection.

a Safety population defined as all patients who received at least one dose of study drug.

b Erysipelas.

 Please note, the above mentioned dosing schedule IXEQ2W is not consistent with the approved dosing schedule for axial spondyloarthritis in the Taltz summary of product characteristics. Please refer to the Taltz summary of product characteristics for approved dosing.1

Integrated Safety Data

An integrated safety analysis was conducted from all ixekizumab axSpA exposures (N=932; PY=1849.0) across 4 axSpA trials (including AS/r-axSpA and nr-axSpA) as of March 19, 2020. The proportion of patients with

  • any infection was 54.8% [IR=27.6 per 100 PYs of exposure]

  • serious infections was 2.1% [IR=1.1 per 100 PYs of exposure]

  • all Candida infections was 2.8% [IR=1.4 per 100 PYs of exposure], and 

  • opportunistic infections (including oral candidiasis, hepatitis B reactivation, invasive herpes simplex, and herpes zoster) was 1.8% [IR=0.9 per 100 PYs of exposure].6,11

The IR of infections decreased over time.11

References

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

2. Papp KA, Bachelez H, Blauvelt A, et al. Infections from seven clinical trials of ixekizumab, an anti-interleukin-17A monoclonal antibody, in patients with moderate-to-severe psoriasis. Br J Dermatol. 2017;177(6):1537-1551. http://dx.doi.org/10.1111/bjd.15723

3. Griffiths CEM, Reich K, Gooderham M, et al. Long-term safety of ixekizumab in patients with moderate-to-severe psoriasis up to 5 years: pooled data from 16 clinical trials. Poster presented at: 29th Annual Meeting of the European Academy of Dermatology and Venereology (EADVirtual); October 29-31, 2020.

4. 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

5. 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 randomised, 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

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

7. Genovese MC, Mysler E, Tomita T, et al. Safety of ixekizumab in adult patients with plaque psoriasis, psoriatic arthritis and axial spondyloarthritis: data from 21 clinical trials. Rheumatology (Oxford). Published online May 25, 2020. https://doi.org/10.1093/rheumatology/keaa189

8. Deodhar A, Poddubnyy D, Pacheco-Tena C, et al. Efficacy and safety of ixekizumab in the treatment of radiographic axial spondyloarthritis: sixteen-week results from a phase III randomized, double-blind, placebo controlled trial in patients with prior inadequate response to or intolerance of tumor necrosis factor inhibitors. Arthritis Rheumatol. 2019;71(4):599-611. http://dx.doi.org/10.1002/art.40753

9. van der Heijde D, Cheng-Chung Wei J, Dougados M, et al. Ixekizumab, an interleukin-17A antagonist in the treatment of ankylosing spondylitis or radiographic axial spondyloarthritis in patients previously untreated with biological disease-modifying anti-rheumatic drugs (COAST-V): 16 week results of a phase 3 randomised, double-blind, active-controlled and placebo-controlled trial. Lancet. 2018;392(10163):2441-2451. http://dx.doi.org/10.1016/s0140-6736(18)31946-9

10. Deodhar A, van der Heijde D, Gensler LS, et al. Ixekizumab for patients with non-radiographic axial spondyloarthritis (COAST-X): a randomised, placebo-controlled trial. Lancet. 2020;395(10217):53-64. http://dx.doi.org/10.1016/S0140-6736(19)32971-X

11. Schwartzman S, Sandoval D, Kronbergs A, et al. Long-term safety profile of ixekizumab treatment on patients with axial spondyloarthritis. Poster presented at: American College of Rheumatology/ARP 2020 Annual Scientific Meeting (Virtual); November 5-9, 2020.

Glossary

AS/r-axSpA = ankylosing spondylitis/radiographic axial spondyloarthritis

axSpA = axial spondyloarthritis

IR = incidence rate

nr-axSpA = nonradiographic axial spondyloarthritis

PY = patient-years

Q4W = every 4 weeks

SAE = serious adverse event

TB = tuberculosis

Datum fӧr senaste ӧversyn 2020 M10 20


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