Taltz® (ixekizumab): Användning på patienter med psoriasis och psoriasisartrit som har lupus och TEAE från lupus

Use in Patients with Lupus

Exclusion and Discontinuation Criteria Related to Lupus

In the ixekizumab phase 3 clinical trials in psoriasis and PsA, patients developing symptoms suggestive of a lupus-like syndrome and testing positive for antibodies against double-stranded DNA were required to discontinue from the studies.^1,2

• Rationale: In accordance with potential risks associated with immunosuppressive agents, a discontinuation rule for patients who develop symptoms suggestive of lupus-like syndrome and are positive for antibodies against double-stranded DNA was added to limit potential safety risks to these patients.²

In the ixekizumab phase 3 clinical trials in axSpA (including AS/r-axSpA and nr-axSpA), patients with a history of lupus were excluded.^3,4

Treatment-Emergent Adverse Events During Clinical Trials

In ixekizumab clinical trials, TEAEs were evaluated using MedDRA. This response includes TEAEs reported that include the term "lupus."²

Lupus-Related Treatment-Emergent Adverse Events

Psoriasis Trials

Within the overall safety database across 14 psoriasis trials as of March 21, 2019 (N=6091 patients exposed to ixekizumab accounting for 17499.3 PYs of exposure), there was 1 report of chronic cutaneous lupus erythematosus that led to study drug discontinuation.²

Psoriatic Arthritis Trials

Within the overall safety database across 4 PsA trials as of March 21, 2019 (N=1401 patients exposed to ixekizumab accounting for 2228.6 PYs of exposure), there were no TEAE reports of any of the MedDRA preferred terms containing the term "lupus."²

Axial Spondyloarthritis Trials

Within the overall safety database across 4 axSpA (including AS/r-axSpA and nr-axSpA) trials as of August 22, 2019 (N=932 patients exposed to ixekizumab accounting for 1571.0 PYs of exposure), there were no TEAE reports of any of the MedDRA preferred terms containing the term "lupus."²

Anti-Double-Stranded DNA Antibodies

Screening and testing for double-stranded DNA antibody during ixekizumab trials were not routinely done.^1,2 Within the overall safety database as of March 21, 2019 (for psoriasis and PsA) and August 22, 2019 (for axSpA) there were no TEAE reports of any MedDRA preferred term that included "double-stranded DNA antibody."²

Antinuclear Antibodies

Laboratory tests for antinuclear antibodies were not routinely performed in ixekizumab trials, although antinuclear antibody was listed in the study protocols as a hepatic monitoring test for treatment emergent abnormalities.^1,2 Within the overall psoriasis safety database as of March 21, 2019 there was 1 TEAE report of "antinuclear antibody positive."²

Within the overall PsA and axSpA databases as of March 21, 2019 (for PsA) and August 22, 2019 (for axSpA), there were no reports of any MedDRA preferred term that included "antinuclear antibody."²

Post-Marketing Adverse Event Reporting Information

Adverse events related to lupus that have been reported to Lilly during postmarketing as of March 22, 2019 include 

• cutaneous lupus erythematosus

• lupus-like syndrome 

• systemic lupus erythematosus, and

• systemic lupus erythematosus rash.

These adverse events have been reported very rarely.²

Spontaneous reporting of adverse events can be highly variable and is not appropriately controlled clinical information on
which to base an assessment of whether a particular drug product caused an event. Spontaneous reporting is also limited in
usage due to bias in reporting, including incomplete information concerning the patient (that is, unknown medical history),
unknown concomitant medications and disease states, and under-reporting.

References

1. 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

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

3. 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

4. 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

Glossary

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

axSpA = axial spondyloarthritis

Lilly = Eli Lilly and Company

MedDRA = Medical Dictionary for Regulatory Activities

nr-axSpA = nonradiographic axial spondyloarthritis

PsA = psoriatic arthritis

PY = patient-years

TEAE = treatment-emergent adverse event