Rheumatoid Arthritis

Persistence with TNFi Monotherapy After Achieving Disease Control on Combination Therapy

Emily Pond
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Joint or cervical spine ankylosis may occur in RA.1 Joint ankylosis usually affects small joints of the hand, wrists, ankle, or forefoot. Although joint ankylosis was once common, widespread DMARD use has nearly eliminated this complication. Studies suggest that bone ankylosis is infrequent (0.8%) and usually occurs in patients with long-standing RA.1 Patients with joint ankylosis of the wrist appear more likely to develop cervical ankylosis.1 The reported prevalence of cervical spine ankylosis ranges from 9% to 80%, depending on the imaging modality used.1 Patients develop bony erosions, ligamentous laxity, and complete fusion.8 Ankylosis of the cervical facet joints typically occurs at the atlanto-occipital and atlanto-axial joints.9 Patients are often asymptomatic, but may have pain, neuropathy, or severe myelopathy and require surgical intervention. Use of DMARDs appears to prevent cervical ankylosis, but does not prevent its progression.8

Joint or cervical spine ankylosis may occur in RA.1 Joint ankylosis usually affects small joints of the hand, wrists, ankle, or forefoot. Although joint ankylosis was once common, widespread DMARD use has nearly eliminated this complication. Studies suggest that bone ankylosis is infrequent (0.8%) and usually occurs in patients with long-standing RA.1

Patients with joint ankylosis of the wrist appear more likely to develop cervical ankylosis.1 The reported prevalence of cervical spine ankylosis ranges from 9% to 80%, depending on the imaging modality used.1 Patients develop bony erosions, ligamentous laxity, and complete fusion.8 Ankylosis of the cervical facet joints typically occurs at the atlanto-occipital and atlanto-axial joints.9 Patients are often asymptomatic, but may have pain, neuropathy, or severe myelopathy and require surgical intervention. Use of DMARDs appears to prevent cervical ankylosis, but does not prevent its progression.8

This retrospective study of registry data reflecting real-world practice indicates patients who achieve remission/LDA with combination csDMARD and TNFi therapy may successfully transition to TNFi monotherapy.

Study data published in Rheumatology International identified correlates of persistence on tumor necrosis factor inhibitor (TNFi) monotherapy among patients with rheumatoid arthritis (RA) who achieved disease control with combination therapy. Patients who received etanercept were less likely than patients on other TNFis to require reintroduction of a conventional synthetic disease-modifying antirheumatic drug (csDMARD). Additionally, those who achieved remission with combination therapy had better persistence than patients who achieved low disease activity (LDA).

Investigators abstracted data from the Corrona registry, a prospective observational cohort of patients with physician-confirmed RA from 177 private practices around the United States. A retrospective analysis was conducted of patients who enrolled in the Corrona registry between October 1, 2001 and August 31, 2017. Eligible participants were adult patients (≥ 18 years) who had achieved remission or LDA on combination therapy with TNFi and csDMARD and subsequently discontinued the csDMARD. The index date was date of csDMARD discontinuation. The primary outcome was persistence on TNFi monotherapy in the 6 and 12 months after index date. Persistence was defined as continuous use of the index monotherapy drug without any treatment gap exceeding 30 days. Logistic regression models were used to identify correlates of persistence at 6 and 12 months. Models were adjusted for age, sex, race/ethnicity, disease duration, prior biological DMARD (bDMARD) exposure, and comorbid conditions.

The study cohort comprised 617 patients who discontinued csDMARD therapy and continued with TNFi monotherapy. Of these patients, 182 were on etanercept monotherapy and 435 were on monotherapy with other TNFis. Baseline demographic characteristics were similar between these 2 medication groups, though a greater proportion of patients on etanercept had prior bDMARD exposure compared to patients on another TNFi (80.2% vs 63.0%). Overall persistence at 6 months was 56% among those on etanercept monotherapy and 45% among those on other TNFi monotherapy (P =.02). At 12 months, persistence remained higher in the etanercept group compared to the other TNFis group (46% vs 33%; P =.03).

After 6 months, the non-etanercept group was more likely to require reintroduction of csDMARDs than the etanercept group (45% vs 35%). This difference persisted after adjustments for prior bDMARD exposure. In multivariable models, being in remission at the index date was the key predictor of persistence on any TNFi monotherapy. Patients in remission at the index date were twice as likely as their comparators with LDA to remain on etanercept or another TNFi at 6 months. Increased disease activity and a history of cardiovascular disease were each associated with lower likelihood of persistence.

These results suggest that a subset of patients who achieve remission or LDA with combined csDMARD and TNFi are able to successfully transition to TNFi monotherapy. Persistence with this monotherapy was strongly associated with remission over LDA and etanercept over other TNFis. “In this real-world setting, etanercept monotherapy was associated with greater persistence than was observed for other TNFi monotherapy, and a lower likelihood of requiring reintroduction of a csDMARD,” investigators wrote.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Pappas DA, Litman HJ, Lesperance T, et al. Persistence on biologic DMARD monotherapy after achieving rheumatoid arthritis disease control on combination therapy: retrospective analysis of corrona registry data. Rheumatol Int. Published online Sept 2, 2020. doi:10.1007/s00296-020-04667-5

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