Male sex, major response within first year strongly predict long-term TNFi survival
There is high long-term retention of the first tumour necrosis factor inhibitor (TNFi) administered to patients with spondyloarthritis (SpA), particularly for males with axial disease, reports a study. Major response within the first year of treatment is the strongest predictor of long-term TNFi survival.
“We report a rather favourable 5- and 10-year TNFi survival rate in patients with SpA,” researchers said. “When first-year clinical responses for axial or peripheral disease were included in the multivariate models of drug survival, they were the strongest independent predictors.”
Of the 1,077 patients, 404 (37.5 percent) discontinued treatment (follow-up, 4,288 patient-years). Drug survival for 10 years was 49 percent. Unadjusted analyses revealed higher TNFi survival in patients with ankylosing spondylitis (AS) compared to undifferentiated (u)SpA and psoriatic arthritis (PsA; significant beyond the first 2.5 and 7 years; p=0.003 and p<0.001, respectively), and in patients treated for isolated axial vs peripheral arthritis (p=0.001). [J Rheumatol 2018;45:785-794]
Male sex predicted longer TNFi survival in all multivariable analyses. In PsA and in patients with peripheral arthritis, methotrexate use was a predictor. Absence of peripheral arthritis and use of a monoclonal antibody (as opposed to nonantibody TNFi) were independent predictors of longer TNFi survival in axial disease due to lower rates of inefficacy.
The strongest predictor of longer therapy retention was the achievement of major responses during the first year in either axial or peripheral arthritis (hazard ratio [HR], 0.33; 95 percent CI, 0.26–0.41 for Ankylosing Spondylitis Disease Activity Score inactive disease; HR, 0.35; 0.24–0.50 for 28-joint Disease Activity Score remission).
“A crude comparative analysis of TNFi survival between individual SpA subtypes showed a time-dependent association, with ultimately higher retention rates in AS versus uSpA and PsA patients,” researchers said.
“We thus support close disease activity monitoring as a valuable tool to predict long-term outcomes,” they added.
Likewise, a study by Lie and colleagues found a higher retention rate in AS vs uSpA. However, other studies with shorter follow-up found a comparable TNFi drug survival between patients with PsA and AS. [Arthritis Res Ther 2006;8:R72; Arthritis Rheum 2008;59:234-240; Ann Rheum Dis 2015;74:970-978; Arthritis Care Res 2017;69:867-874]
“These discrepancies could possibly be attributed to different study populations as well as to varying physician therapy withdrawal criteria,” researchers explained.
One notable result of the present study was the association between the absence of peripheral arthritis and longer drug survival in the whole SpA, as well as in patients with AS, which was due to less chance of inefficacy withdrawals.
However, data on the effect of peripheral involvement on TNFi retention are sparse. A study by Kristensen and colleagues found that peripheral disease predicted more favourable TNFi retention in AS at 2 years of follow-up. [Arthritis Care Res 2010;62:1362-1369]
“Shorter follow-up and other factors may be implicated in this difference, and more studies are necessary, especially with the growing group of patients classified as peripheral SpA becoming more clinically significant,” researchers said.
This study analysed patients with SpA in the Hellenic Registry of Biologic Therapies, a prospective multicentre observational cohort, starting their first TNFi between 2004 and 2014. Kaplan-Meier curves and Cox regression models were used.