Taltz ® (ixekizumab) injektion

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Taltz® (ixekizumab): Patienter med tidigare malignitet

Ixekizumab har inte studerats hos patienter med malignitet eller tidigare malignitet. Information om maligniteter som uppstår under behandling finns tillgänglig.

Short Answer Summary

Non-clinical studies have not been conducted to evaluate the carcinogenic or mutagenic potential of ixekizumab.1

Psoriasis may be associated with increased risk of malignancy.2-4 Geller et al summarized the baseline malignancy risk in psoriasis patients as well as the risk of malignancy with psoriasis treatments.5

The overall rates of malignancies in ixekizumab studies in psoriasis were consistent with the incidence rates reported in observational studies of psoriasis patients.6,7

Rates of malignancy did not increase over time with longer exposures to ixekizumab in the psoriasis, PsA, or axSpA (including AS/r-axSpA and nr-axSpA) clinical trial programs.8

Detailed Information

Ixekizumab Use in Patients with a Malignancy or History of Malignancy

Ixekizumab product labeling does not contain a contraindication for use in patients with a malignancy or history of malignancy. However, the use of ixekizumab in this population has not been studied.

Clinical Trial Exclusion Criteria

  • Active, or a history of malignant disease was an exclusion criterion in the pivotal psoriasis UNCOVER clinical trials and in the pivotal PsA SPIRIT clinical trials (history of malignant disease within 5 years prior to baseline for SPIRIT-P2 and later trials, including IXORA psoriasis studies, SPIRIT-H2H in PsA, and axSpA trials).

  • Patients were excluded if they had current or a history of lymphoproliferative disease, or signs or symptoms of lymphoproliferative disease (limited to within 5 years of baseline for later trials).

  • Patients with successfully treated basal-cell carcinoma (no more than 3), squamous-cell carcinoma of the skin, or cervical carcinoma in situ, with no evidence of recurrence within the 5 years prior to baseline were allowed to participate in the pivotal psoriasis and PsA studies.

  • Note: This is not an all-inclusive list of exclusion criteria, but rather a list of those exclusion criteria related to malignancy.9-15

Clinical Trial Discontinuation Criteria 

  • The clinical trial protocols required patients who developed a malignancy to discontinue the studies.

  • Patients were allowed to continue if they developed no more than 2 NMSC over any 12-month period during the studies.

  • Note: This is not an all-inclusive list of discontinuation criteria, but rather discontinuation criteria related to malignancy.11,16

Treatment-Emergent Malignancies in Clinical Trials

All Ixekizumab Psoriasis Exposures

An integrated safety analysis of 15 adult and 1 pediatric psoriasis clinical trials as of March 19, 2020 (all patients exposed to ixekizumab (N=6645) accounting for 17,902 PY of exposure) assessed cumulative safety experience covering up to 5 years of exposure (Table 1).17

Table 1. Malignancies Reported in All Ixekizumab Exposures Across 16 Psoriasis Trials16,17

 

All Ixekizumab Psoriasis Exposures Integrated Analysis Set
N=6645; 17,902 PY of Exposure
n (%) [IR]

Patients reporting ≥1 malignancy TEAE

139 (2.1) [0.8]

NMSCa

54 (0.8) [0.3]

Malignancies excluding NMSC

92 (1.4) [0.5]

Abbreviations: IR = incidence rate per 100 patient-years of exposure; NMSC = nonmelanoma skin cancer; PY = patient-years; TEAE = treatment-emergent adverse event. 

a No patients discontinued from the studies due to NMSC.

Malignancies excluding NMSC that were reported more than one time consisted of

  • prostate cancer (n=12)

  • squamous cell carcinoma (n=7)

  • invasive ductal breast carcinoma (n=5)

  • colon cancer (n=4)

  • lung cancer metastatic (n=3)

  • rectal adenocarcinoma (n=3)

  • B-cell lymphoma (n=2)

  • breast cancer (n=2)

  • intraductal proliferative breast lesion (n=2)

  • invasive breast carcinoma (n=2) 

  • invasive lobular breast carcinoma (n=2), and

  • renal cell carcinoma (n=2).16

Rates of malignancy did not increase over time during longer exposures to ixekizumab.17

All Ixekizumab Psoriatic Arthritis Exposures

An integrated safety analysis of 4 PsA clinical trials as of March 19, 2020 that included all patients exposed to ixekizumab (N=1401 accounting for 2247.7 PY of exposure) assessed cumulative safety experience covering up to 3 years of exposure (Table 2).16

Table 2. Malignancies Reported in All Ixekizumab Exposures Across 4 Psoriatic Arthritis Clinical Trials16

 

All Ixekizumab Psoriatic Arthritis Exposures Integrated Analysis Set
N=1401; 2247.7 PY of Exposure
n (%) [IR]

Patients reporting ≥1 malignancy TEAE

15 (1.1) [0.7]

NMSCa

9 (0.6) [0.4]

Malignancies excluding NMSC

7 (0.5) [0.3]

Abbreviations: IR = incidence rate per 100 patient-years of exposure; NMSC = nonmelanoma skin cancer; PY = patient-years; TEAE = treatment-emergent adverse event.

a One patient with basal cell carcinoma discontinued from the study.

Of malignancies excluding NMSC, there was 1 case each of 

  • prostate cancer 

  • breast cancer 

  • gastrointestinal stromal tumor 

  • invasive ductal breast carcinoma 

  • malignant melanoma in situ 

  • metastatic renal cell carcinoma, and

  • papillary thyroid cancer.16

Rates of malignancy did not increase over time during longer exposures to ixekizumab.8

All Ixekizumab Axial Spondyloarthritis Clinical Trials

An integrated safety analysis of 4 axSpA (including AS/r-axSpA and nr-axSpA) clinical trials as of March 19, 2020 that included all patients exposed to ixekizumab (N=932 accounting for 1849.0 PY of exposure) assessed cumulative safety experience covering up to 3 years of exposure (Table 3).18

Table 3. Malignancies Reported in All Ixekizumab Exposures Across 4 Axial Spondyloarthritis Trials16,18

 

All Ixekizumab Axial Spondyloarthritis Exposures Integrated Analysis Set
N=932; 1849.0 PY of Exposure
n (%) [IR]

Patients Reporting ≥1 malignancy TEAE

7 (0.8) [0.4]

NMSC

0

Malignancies excluding NMSC

7 (0.8) [0.4]

Abbreviations: IR = incidence rate per 100 patient-years of exposure; NMSC = nonmelanoma skin cancer; PY = patient-years; TEAE = treatment-emergent adverse event.

Of malignancies excluding NMSC, there was 1 case each of 

  • abdominal neoplasm

  • acute promyelocytic leukemia 

  • chronic lymphocytic leukemia 

  • anal cancer 

  • breast cancer 

  • bladder cancer, and

  • ovarian cancer.16,18

References

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

2. Alexandrescu DT, Riordan NH, Ichim TE, et al. On the missing link between inflammation and cancer. Dermatol Online J. 2011;17(1):10. http://escholarship.org/uc/item/0gf628ss

3. Pouplard C, Brenaut E, Horreau C, et al. Risk of cancer in psoriasis: a systematic review and meta-analysis of epidemiological studies. J Eur Acad Dermatol Venereol. 2013;27(suppl 3):36-46. http://dx.doi.org/10.1111/jdv.12165

4. Kimball AB, Schenfeld J, Accortt NA, et al. Cohort study of malignancies and hospitalized infectious events in treated and untreated patients with psoriasis and a general population in the United States. Br J Dermatol. 2015;173(5):1183-1190. http://dx.doi.org/10.1111/bjd.14068

5. Geller S, Xu H, Lebwohl M, et al. Malignancy risk and recurrence with psoriasis and its treatments: a concise update. Am J Clin Dermatol. 2018;19(3):363-375. http://dx.doi.org/10.1007/s40257-017-0337-2

6. Margolis D, Bilker W, Hennessy S, et al. The risk of malignancy associated with psoriasis. Arch Dermatol. 2001;137(6):778-783. http://www.ncbi.nlm.nih.gov/pubmed/11405770

7. Strober B, Phillip S, Wilhelm S, et al. Safety and tolerability of ixekizumab: analysis of malignancies in 7 clinical studies of moderate-severe plaque psoriasis. Poster presented at: European Academy of Dermatology and Venereology 2015; October 7-11, 2015; Copenhagen, Denmark.

8. 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

9. 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

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. 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

12. Langley RG, Papp K, Gooderham M, et al. Efficacy and safety of continuous every-2-week dosing of ixekizumab over 52 weeks in patients with moderate-to-severe plaque psoriasis in a randomized phase III trial (IXORA-P). Br J Dermatol. 2018;178(6):1315-1323. http://dx.doi.org/10.1111/bjd.16426

13. 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

14. 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

15. 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

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

17. 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.

18. 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

NMSC = nonmelanoma skin cancer

nr-axSpA = nonradiographic axial spondyloarthritis

PsA = psoriatic arthritis

PY = patient-years

Datum fӧr senaste ӧversyn 2020 M10 20


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