Association of Secukinumab Treatment With Tuberculosis Reactivation in Patients With Psoriasis, Psoriatic Arthritis, or Ankylosing Spondylitis

Abstract

IMPORTANCE Approximately one-quarter of the global population have latent tuberculosis infection (LTBI), and tuberculosis (TB) is accountable for more than 1.5 million deaths annually. Methotrexate, cyclosporine, and tumor necrosis factor inhibitors may be associated with increased risk of TB and LTBI reactivation, although data are limited on the risks of TB with use of newer biologics. OBJECTIVE To assess the association of secukinumab with reporting of active TB development, TB reactivation, and LTBI activation as an adverse event (AE) in patients with psoriasis, psoriatic arthritis, or ankylosing spondylitis. DESIGN, SETTING, AND PARTICIPANTS This qualitative study pooled data from 28 clinical trials of secukinumab used in psoriasis (17 phase 3 or 3b and 2 phase 4 trials), psoriatic arthritis (5 phase 3 trials), and ankylosing spondylitis (4 phase 3 trials). A search of the Novartis Secukinumab Compound Pool Database was conducted for the 28 trials. All trial participants who had received at least 1 approved subcutaneous dose of secukinumab (150 mg or 300 mg) were included. Before randomization in these trials, patients underwent screening for TB. Patients with active TB were excluded, and patients with LTBI were treated according to local guidelines. Data were analyzed from the start of treatment in the individual studies through December 25, 2018. MAIN OUTCOMES AND MEASURES Reporting of active TB or LTBI as an AE over a 5-year period using exposure-adjusted incidence rates (EAIR; incidence rates per 100 patient-years). RESULTS A total of 12 319 patients were included, of whom 8819 patients had psoriasis (71.6%; 5930 men [67.2%]; mean [SD] age, of 44.9 [13.5] years), 2523 had psoriatic arthritis (20.5%; 1323 women [52.4%]; mean [SD] age, 48.8 [12.1] years), and 977 had ankylosing spondylitis (7.3%; 658 men [67.3%]; mean [SD] age, 42.3 [11.9] years). In the total population, 684 patients (5.6%) had tested positive for LTBI at screening. Over 5 years, LTBI as an AE during secukinumab treatment was reported in 13 patients (0.1% of 12 319). Of these 13 patients, 6 had a prior positive LTBI test result, and 7 were newly diagnosed as having LTBI. Four of the 7 patients had psoriasis (EAIR, 0.03; 95% CI, 0.01-0.07), 1 had psoriatic arthritis (EAIR, 0.02; 95% CI, 0.00-0.11), and 2 had ankylosing spondylitis (EAIR, 0.08; 95% CI, 0.01-0.28). No cases of active TB were reported. CONCLUSIONS AND RELEVANCE This study found that LTBI reported as an AE after secukinumab treatment was uncommon and appeared to support the use of secukinumab in chronic systemic inflammatory conditions.

Secukinumab: A Review in Psoriatic Arthritis

“…No cases of active tuberculosis (TB) or latent TB infection reactivation were reported in the secukinumab clinical trial programme [ 50 ]. However, patients should be evaluated for TB infection prior to initiating secukinumab, and should be closely monitored for signs and symptoms of active TB during and after treatment [ 6 ].…”

Secukinumab in axial spondyloarthritis: a narrative review of clinical evidence

“…Anti-TNF biologics have linked to an increased risk of TB and latent TB infection (LBTI); meanwhile, there are limited data available that report the relationship between TB and biologics targeting other biologic pathways, such as IL-17. 74 A qualitative study comprising 12,319 patients with PsO ( n = 8819), PsA ( n = 2523) or r-axSpA ( n = 977) showed that LBTI as an AE was uncommon after treatment with secukinumab. 74 Over 5 years, LBTI during secukinumab treatment was reported in 0.1% of patients ( n = 13).…”

“… 74 A qualitative study comprising 12,319 patients with PsO ( n = 8819), PsA ( n = 2523) or r-axSpA ( n = 977) showed that LBTI as an AE was uncommon after treatment with secukinumab. 74 Over 5 years, LBTI during secukinumab treatment was reported in 0.1% of patients ( n = 13). 74 …”

Systematic Review and Meta-Analysis of Inflammatory Bowel Disease Adverse Events with Anti-Interleukin 17A Agents and Tumor Necrosis Factor Inhibitors in Rheumatic Disease and Skin Psoriasis

“…In one ixekizumab trial (SPIRIT-P2), and three secukinumab trials (FIXTURE, ERASURE, and NCT03066609), we classified events by contacting the trial sponsor or with a subsequent publication [31][32][33]. We were unable to classify IBD events in four secukinumab trials (ALLURE, FUTURE-1, FUTURE-2, MEASURE-4) and two anti-TNF trials ( [39], ABILITY-3) so assumed these events to be new IBD, adding five new IBD events on secukinumab, four on anti-TNF and two on placebo [34][35][36][37][38][39].…”