Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with ixekizumab. Do not administer to patients with active TB infection. Initiate treatment of latent TB prior to administering ixekizumab. Consider anti-TB therapy prior to initiating ixekizumab in patients with history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Patients receiving ixekizumab should be monitored closely for signs and symptoms of active TB during and after treatment.1

Reactivation of latent TB has been reported with the use of other immunosuppressive agents.2,3

Integrated data from clinical trials of ixekizumab in adult patients with psoriasis, psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) showed no confirmed cases of TB reactivation.4,5

Patients were screened for TB using chest x-rays, purified protein derivative skin tests, or QuantiFERON®-TB Gold.6,7 Patients who

• tested negative were retested yearly, with the exception of axSpA trials, in which no retesting for TB was required
• tested positive for TB but had no evidence of TB infection were allowed to participate in the trial if they received at least 4 weeks of appropriate LTBI therapy, with the completion of the therapy during the course of the study
• had evidence or suspicion of active TB were excluded from ixekizumab clinical trials, and
• had household contact with a person with active TB were excluded, unless appropriate and documented prophylaxis for TB was given.6-8

In an integrated safety analysis of all ixekizumab adult psoriasis exposures (N=6892; 18,025.7 patient-years [PYs] of exposure) across 17 plaque psoriasis trials as of March 2022, latent TB was reported in 106 (1.5%) patients (incidence rate [IR]=0.6 per 100 PYs). There were no confirmed cases of TB reactivation reported.9-11

A positive TB test led to discontinuation of study drug in 67 patients. Among them, 1 case was reported as TB by the investigator (occurred in a patient who was previously treated for latent TB, but without symptoms and treated with isoniazid, so did not indicate active disease). There was 1 case of pulmonary TB. This patient had a diagnosis of active TB, and it was not considered a reactivation.9

There were no existing latent TB cases that presented any sign of active TB disease, and there were no fatal cases due to TB.9

In an integrated safety analysis of all ixekizumab PsA exposures (N=1401; 2247.7 PYs of exposure) across 4 PsA trials as of March 2022, latent TB was reported in 35 (2.5%) patients (IR=1.6 per 100 PYs). No confirmed cases of TB reactivation were reported.10,11

Upon annual TB testing, 35 patients who were originally negative at entry in the trials had a positive TB test (2.5%, IR=1.6 per 100 PYs). A positive TB test led to discontinuation in 10 patients according to protocols. The remaining 25 patients who did not discontinue the trial received treatment for latent TB infection prior to resuming study drug.12 

Most new cases of latent TB occurred in patients from countries at high risk of TB.12 

Data revealed no existing latent TB cases who presented any signs of active TB disease. No cases of latent TB resulted in death.12

In an integrated safety analysis of all ixekizumab axSpA (including ankylosing spondylitis/radiographic axial spondyloarthritis [AS/r-axSpA] and nonradiographic axial spondyloarthritis [nr-axSpA]) exposures (N=932; 2097.7 PYs of exposure) across 4 axSpA trials as of March 2022, latent TB was reported in 2 (0.2%) patients (IR=0.1 per 100 PYs).10,11 No confirmed cases of TB reactivation were reported.10,11,13

In the postmarketing setting, serious bacterial, viral, and fungal opportunistic infections have been reported in patients receiving IL-17 inhibitors including ixekizumab. Bacterial opportunistic infections, including pulmonary tuberculosis, have been reported. Because the reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to ixekizumab exposure.1

Spontaneous reporting of adverse events can be highly variable and is not controlled clinical information on which to assess causality of a drug to an adverse event. Spontaneous reporting has limitations due to bias in reporting including incomplete information concerning the patient. In addition, the Global Patient Safety (GPS) spontaneous database may include reports of adverse events for products that are available from a variety of manufacturers. When verification of product manufactured by Eli Lilly and Company is not obtainable, these cases are included in the spontaneous database.

TALTZ® (ixekizumab) injection, for subcutaneous administration, Lilly

The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).