Novel therapies provide options for patients with spondyloarthritides
ATLANTA — Certolizumab pegol and bimekizumab were associated with improvements ranging from work productivity to disease activity in patients with spondyloarthritic conditions, according to findings presented in three abstracts at ACR/ARP 2019.
“What we are most excited about at UCB this year is the continued commitment to the spondyloarthritis group of diseases, most importantly, the axial spondyloarthritis diseases,” Jeffrey Stark, MD, head of medical affairs in rheumatology at UCB, told Healio Rheumatology in an interview. “Those patients have huge unmet needs in the U.S. in terms of being under-recognized, inadequately diagnosed and poorly treated.”
Stark zeroed in on two analyses of the C-axSpAnd study in patients treated with certolizumab pegol (Cimzia, UCB) and one study in bimekizumab (UCB).
In one analysis of the C-axSpAnd study, Deodhar and colleagues looked at productivity and work parameters in patients with nonradiographic axial spondyloarthritis. The 3-year, phase 3, double-blind, placebo-controlled trial included 317 patients randomly assigned certolizumab pegol plus nonbiologic background medication or placebo plus nonbiologic background medication. The certolizumab regimen was administered at 400 mg at weeks 0, 2, and 4, followed by 200 mg every 2 weeks through 52 weeks. There were 159 patients in the active therapy arm and 158 in the placebo arm.
Participants completed the arthritis-specific Work Productivity Survey to determine outcomes regarding household productivity and social participation.
Week 12 results showed that active treatment was associated with improvement in work absenteeism compared with placebo, 0.9 vs 2.1 days missed per month. By week 52, the rates were 0.3 missed days per month with certolizumab pegol and 2 days per month with placebo.
“Work productivity and household productivity are especially important for the nonradiographic patient, who, on average, develops their disease at an age of 28,” Stark said. “These patients are at the earliest years of their work productivity.”
In a post-hoc analysis of the C-axSpAnd study, Kay and colleagues investigated whether earlier initiation of certolizumab pegol could yield clinical and patient-reported outcomes among the 159 patients who underwent active therapy.
For this particular analysis, the researchers stratified the patients withnonradiographic axial spondyloarthritis by baseline symptom duration with a break point at 5 years, and for key clinical outcomes reported at a break point of 3 years.
Ankylosing Spondylitis Disease Activity Score – Major Improvement (ASDAS-MI) served as a key clinical endpoint, along with Assessment in SpondyloArthritis international Society 40% response (ASAS40), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), nocturnal spinal pain, fatigue (BASDAI Q1), morning stiffness (average of BASDAI Q5 and Q6). To assess patient-reported outcomes, patients completed the 36-Item Short Form Survey (SF-36) physical and mental component summary.
Results for ASDAS-MI at week 12 showed that 46.3% of patients with a symptom duration shorter than 5 years responded to active therapy, while just 24.1% of those with symptoms longer than 5 years responded. By 52 weeks, ASDAS-MI response rates were 55% for patients with symptoms shorter than 5 years and 39.2% for those with symptoms longer than 5 years.
Similar trends were reported across outcome measures, including ASAS40, BASDA, nocturnal spinal pain, fatigue, morning stiffness and SF-36.
“While the clinical community might think that all patients are in a window of opportunity for optimal treatment if they do not have structural progression, in fact, we demonstrated that those patients who are treated earlier attain superior outcomes compared to those who are treated later,” Stark said. “The cutoff in that study was 5 years, but the diagnostic delay among AxSpa patients in the U.S. is closer to 8 or 9 years.”
Shifting to bimekizumab, van der Heijde and colleagues investigated the drug in a cohort of 303 patients with active ankylosing spondylitis. ASAS40 response rate at week 12 served as the primary endpoint. The ACR presentation included ongoing efficacy findings for patients assigned a subcutaneous injection of bimekizumab at 16 mg, 64 mg, 160 mg, 320 mg, or placebo every 4 weeks for 12 weeks, which was deemed the double-blind period. After that patients in the 16 mg, 64 mg and placebo groups were re-randomized to bimekizumab 160 mg or 320 mg every 4 weeks through 48 weeks.
Week 12 results showed that ASAS40 outcomes were 29.5% for the 16 mg dose, 42.6% for the 64 mg dose, 46.7% for the 160 mg dose, 45.9% for 320 mg, and 13.3% for placebo (P < .05).
ASAS40 response rates among bimekizumab-treated patients ranged from 35.5% to 64% at week 48.
Safety data showed that 77.6% of the cohort experienced treatment-emergent adverse events, with 6.6% discontinuing due to these events. The one fatality in a patient treated with the 160 mg dose was deemed to be unrelated to bimekizumab. Nasopharyngitis, bronchitis and pharyngitis topped the list of adverse events, with inflammatory bowel disease and serious infections each occurring in 1.3% of the study population.
“It is important to recognize the mechanism of action of bimekizumab,” Stark said. “While it does target IL-17 pathways, it does so in a completely different method than any other available IL-17 drug.”
Bimekizumab targets IL-17a as well as IL-17f, according to Stark. “In a body of pre-clinical data, we have seen that that blockade has much more intensely suppressing effects on inflammation,” he said. – by Rob Volansky
- Deodhar A. Abstract #1507. Certolizumab pegol improves work and household productivity and social participation over 1 year of treatment in patients with non-radiographic axial spondyloarthritis.
- Kay J. Abstract #936. Earlier treatment of non-radiographic axial spondyloarthritis with certolizumab pegol results in improved clinical and patient-reported outcomes.
- van der Heijde D. Abstract #937. Dual neutralization of IL-17A and IL-17F with bimekizumab in patients with active ankylosing spondylitis: 48-week efficacy and safety results from a phase 2b, randomized, blinded, placebo-controlled, dose-ranging study.
- Presented at: American College of Rheumatology/Association of Rheumatology Professionals Annual Meeting; Nov. 9-13, 2019; Atlanta.
Disclosure: Stark reports being an employee of UCB.