Factors Differ for Early vs Late TNFi Switch in AS Patients

Sara Freeman

September 24, 2021

Older age, higher subjective disease activity, and exercising for more than 120 minutes per week were three factors linked to patients with ankylosing spondylitis (AS) who switched from their original tumor necrosis factor inhibitor (TNFi) treatment within 2 years in a U.S.-based study.

Data from the Prospective Study of Outcomes in Ankylosing Spondylitis (PSOAS) also found that higher levels of inflammation, but not radiographic disease, were linked to patients changing from one TNFi to another, or to an interleukin (IL)-17 inhibitor or Janus kinase (JAK) inhibitor.

Dr John Reveille

"Different factors were associated in AS patients who switch from their initial TNF inhibitor to another TNF inhibitor, IL-17 inhibitor, or JAK inhibitor within 2 years versus after 2 years of treatment," John D. Reveille, MD, professor and vice chair of rheumatology and clinical immunogenetics with McGovern Medical School at UTHealth Houston, said at the 12th International Congress on Spondyloarthritides.

"We're currently looking at different approaches to analyzing these data. And, certainly, this needs need to be looked at in other cohorts," Reveille said.

PSOAS is a prospective observational cohort study that has been looking at predictors of AS severity for almost 20 years. Started in 2002, the study has routinely collected a whole host of data on various demographic and disease-related factors.

The reasoning behind the current analysis of PSOAS data was that a relatively recent study based on a commercial claims database had found that many patients with AS do not remain on their initial TNFi 2 years after initiation. So, Reveille and associates decided to look at the factors that could be influencing whether patients who started a TNFi would remain on their original drug in the PSOAS cohort.

In all, 533 patients from the PSOAS cohort who had at least 2 years of follow-up were included in the analysis. The majority (n = 496) were treated with a TNFi, 34 had received an IL-17 inhibitor, and 3 had received a JAK inhibitor.

Of the 496 patients treated with a TNFi, almost 70% (n = 344) persisted with this treatment for the duration of the study. Of those that switched to another TNFi or IL-17 or JAK inhibitor treatment, 20% (n = 101) did so within 2 years and the remaining 10% (n = 51) after 2 years.

Multinominal logistic regression modeling revealed a number of different factors that were associated with switching within 2 years versus switching after 2 years.

Compared to patients who persisted with treatment throughout the study period, patients who switched from their original TNFi within 2 years were more likely to be older (odds ratio [OR], 2.0 for ≥ 40 vs. < 40 years; P = .002), have a higher Bath Ankylosing Spondyloarthritis Disease Activity Index (BASDAI) score at baseline (OR, 1.73 for ≥ 4 vs. < 4; P = .03), higher C-reactive protein levels (OR, 1.94 for ≥ 0.8 mg/dL vs. < 0.8 mg/dL, P = .004), and greater weekly duration of exercise (OR, 1.95 for ≥ 120 minutes per week vs. < 120; P <.001).

Switchers also were less likely to have severe radiographic disease at baseline, as determined by the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS, OR, 0.63; P = .03), and less likely to be current smokers (OR, 0.69; P < .001).

Factors associated with switching after 2 years versus persisting with treatment were higher baseline BASDAI (OR, 2.31; P = .01), exercising more than 120 minutes per week (OR, 1.66; P = .03), and having more comorbidities (OR, 1.63 for ≥ 2 vs. < 2, P = .04).

However, patients who switched after 2 years were less likely to be depressed (OR, 0.35; P = .002) or to have a longer baseline disease duration (OR, 0.27 for ≥ 20 years vs. < 20 years P < .001).

The association observed between switching within 2 years and lower likelihood of currently smoking was a "little bit puzzling," one delegate said after Reveille's presentation. "The opposite has been shown in the literature, and current smokers seem to be refractory to TNF inhibitor therapy," the delegate observed.

"I was confounded when I saw the data," Reveille acknowledged. Because this was an observational study, this finding needs more investigation, he agreed. "Interestingly, we have seen this negative association with some other parameters, too," he added.

The HLA-B27 carrier and radiographic status were carefully checked, so there should not be a problem with the diagnosis, Reveille reassured. Further analyses of the findings are now warranted.

Funding for the study was provided by the U.S. Department of Health and Human Services, the National Institutes of Health, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Additional funding was received from the Spondyloarthritis Association of America and Eli Lilly.

Reveille made no personal disclosures; a coauthor of the abstract was an employee of Eli Lilly.

This article originally appeared on MDedge.com, part of the Medscape Professional Network.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.