SPIRIT trials: Ixekizumab proven safe in patients with psoriatic arthritis
Analysis of pooled data from three phase III trials (SPIRIT-P1, -P2 and -P3) reveals that ixekizumab (IXE), a high affinity monoclonal antibody that selectively targets interleukin-17A, is a safe treatment for patients with active psoriatic arthritis (PsA), according to a study presented at the Annual European Congress of Rheumatology by the European League Against Rheumatism (EULAR 2018).
“The safety profile of IXE in patients with PsA is consistent with previous reports as derived from the analysis of the three SPIRIT trials from a large cohort of patients,” researchers said. “No new safety signals were identified with longer IXE treatment exposure.”
Of the 1,118 patients who received IXE (total exposure, 1,373.4 patient-years), four died (0.3 per 100 patient-years) due to cerebrovascular accident, cardiorespiratory arrest, drowning and pneumonia. The most common treatment-emergent adverse events (TEAEs) were the following: injection-site reaction (ISR), upper respiratory tract infection and nasopharyngitis. There was a decrease in incidence rates for TEAEs, including ISRs, over time. [EULAR 2018, abstract SAT0348]
Longer exposure to IXE did not result in clinically meaningful increase in incidence rates of serious AEs, infections, serious infections, hypersensitivity and major adverse cardiovascular events (MACE). Incidence rate was low (1.2 per 100 patient-years) for serious infections, which included pneumonia (0.2 per 100 patient-years), lower respiratory tract infection and oesophageal candidiasis (0.1 per 100 patient-years).
There were no cases of active tuberculosis (TB) reported, but one case of latent TB was deemed serious due to hospitalization for testing to exclude active TB. Opportunistic infections were limited to the following: oral and oesophageal Candida and localized herpes zoster. No cases of deep organ or bloodstream Candida infections were reported.
There was no anaphylaxis recorded, but one patient (0.1 per 100 patient-years) had angioedema. There was also no record of infections temporally associated with grade 2 neutropaenia. However, there were nine patients (0.7 per 100 patient-years) who had MACE.
Furthermore, one case (0.1 per 100 patient-years) of Crohn’s disease (with prior history of irritable bowel syndrome) and of ulcerative colitis were reported, but none of the 12 patients with pre-existing inflammatory bowel disease had an exacerbation with IXE.
Researchers evaluated the safety profile of IXE in patients with active PsA using data pooled from three phase III trials. [ARD 2017;76:79. Lancet 2017;10:2317]
SPIRIT-P1 and -P2 are double-blind trials, in which patients were randomized to placebo, adalimumab (ADA; active reference arm; SPIRIT-P1 only) or 80-mg IXE every 4 (Q4W) or 2 (Q2W) weeks. Placebo and ADA patients were re-randomized to either IXEQ4W or IXEQ2W for the open-label extension period (weeks 24–156), while those who initially received IXE remained on their original dose.
SPIRIT-P3, on the other hand, is an open-label (week 36–64) trial where patients received IXEQ2W followed by a randomized withdrawal period. A 160-mg loading dose of IXE was given to patients in all three trials.
Researchers integrated safety data from all IXE-treated patients (defined as all patients receiving one dose of IXE) included in SPIRIT-P1, -P2 and -P3. Exposure-adjusted incidence rates per 100 patient-years were reported for AEs.