Anti-tumor necrosis factor (TNF) response trajectories demonstrate that the efficacy of anti-TNF therapy can be assessed before the recommended 6 months, facilitating treatment switching when necessary and resulting in overall improved outcomes in rheumatoid arthritis (RA), according to research results published in Rheumatology.

Among patients with RA, researchers sought to identify the different trajectories of disease activity after the initiation of the first anti-TNF medication. Investigators gathered data from the British Society for Rheumatology Biologics Register for RA (BSRBR-RA), a national, prospective, longitudinal, observational study launched in the United Kingdom in 2001.

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Investigators collected data every 6 months for the first 3 years of cohort enrollment, and then every year thereafter. They used Disease Activity Score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) assessments to identify disease activity trajectory by latent class modeling.


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In total, 14,436 patients with RA who started their first anti-TNF therapy were enrolled in BSRBR-RA between 2001 and 2013. Researchers divided patient data into 2 subgroups: 2001 to 2018 (n=13,115) and 2010 to 2013 (n=1321). The overall mean number of DAS28-ESR assessments per patient was 3.5±2.1, with a mean of 184.9±69.9 days between scores and 198.2±75.3 days between enrollment and the first recorded DAS28-ESR.

For the entire cohort, researchers calculated the mean Bayesian information criterion (BIC) for 2-, 3-, 4-, and 5-class latent class mixed models. They found that the 4-class model had the lowest mean BIC, representing the most stable model. Within the 2010 to 2013 subgroup, the most stable model was the 2-class model. Researchers identified 4 distinct response trajectories for the entire cohort and they identified 2 trajectories for the 2001 to 2008 and 2010 to 2013 subgroups. Overall, the greatest DAS28-ESR reduction was achieved by 250 days after starting anti-TNF therapy in all groups.

For the 2-class model, posterior probabilities demonstrated a high likelihood of correct trajectory classification; posterior probabilities for the 4-class model of maximal and minimal trajectory classification were high (>0.7), with substantial and moderate response trajectories being most ambiguous (0.62 and 0.64, respectively). Nonetheless, the maximal response trajectory was uncommon, with only 8.7% of patients achieving the outcome. A majority of patients achieved either a modest or substantial response (55.3% and 32.4%, respectively); only 3.6% of patients were classified as minimal responders.

Study limitations included the observational nature of the study and the potential for recruitment bias despite broad inclusion criteria.

“This is the largest study to identify long-term response trajectories with anti-TNF,” the researchers concluded. “The majority of patients had persistent moderate response, equivalent to maintained DAS28-ESR moderate disease activity.” They added, “Further work is necessary to identify if the results identified for anti-TNF agents are common across all [disease-modifying antirheumatic drugs], and for patients who have switched to second- or third-line biologic agents.”

Disclosure: This clinical trial was supported by AbbVie Inc; Celltrion Healthcare; Hospira, Inc; Merck Sharp & Dohme Corp; Pfizer Inc; Roche; Samsung; Swedish Orphan Biovitrum; and UCB Pharma, Inc. Please see the original reference for a full list of authors’ disclosures.

Reference

Hamann PDH, Pauling JD, McHugh N, Hyrich K, Shaddick G; BSRBR-RA Contributors Group. Early response to anti-TNF predicts long-term outcomes including sustained remission: an analysis of the BSRBR-RA [published online November 12, 2019]. Rheumatology (Oxford). doi:10.1093/rheumatology.kez518