Oral glucocorticoid use in patients with rheumatoid arthritis initiating TNF-inhibitors, tocilizumab or abatacept: Results from the international TOCERRA and PANABA observational collaborative studies

SUMMARY

To evaluate and compare the use of oral glucocorticoids with three classes of bDMARDs in patients with rheumatoid arthritis (RA), the authors included patients from 13 observational registries treated with a TNF-inhibitor, abatacept or tocilizumab and with available information on the use of oral glucocorticoids. The main outcome was oral glucocorticoid withdrawal. A McNemar test was used to analyse the change in the use of glucocorticoids after 1 year. Kaplan-Meier estimates and Cox regressions, adjusted for patient, treatment, and disease characteristics, were used to evaluate glucocorticoid discontinuation in patients with glucocorticoids at baseline. Because of heterogeneity, analyses were done by registers and pooled using random-effects meta-analysis.

A total of 12,334 participants treated with TNF-inhibitors, 2100 with tocilizumab and 3229 with abatacept were included. At one-year, oral glucocorticoid use decreased in all treatment groups (odds ratio for stopping vs. starting of 2.19 [95% CI 1.58; 3.04] for TNF-inhibitors, 2.46 [1.39; 4.35] for tocilizumab; 1.73 [1.25; 2.21] for abatacept). Median time to glucocorticoid withdrawal was ≈2 years or more in most countries, with a gradual decrease over time. Compared to TNF-inhibitors, crude hazard ratios of glucocorticoid discontinuation were 0.65[0.48-0.87] for abatacept, and 1.04 [0.76-1.43] for tocilizumab, and adjusted hazard ratios were 1.1 [0.83-1.47] for abatacept, and 1.30 [0.96-1.78] for tocilizumab.

The authors concluded that initiation of a bDMARD, glucocorticoid use decreased similarly in all treatment groups. However, glucocorticoid withdrawal was much slower than advocated by current international guidelines. More effort should be devoted to glucocorticoid tapering when low disease activity is achieved.

Funding: Two of the collaborations, TOCERRA and PANABA, were funded by Roche and BMS respectively, nevertheless, they did not influence the research questions, results, and conclusions. Sponsors did not participate in the collection or analysis of data and did not have access to the data.

Full article: 10.1016/j.jbspin.2023.105671

Why is it important?

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterised by inflammation and destruction of joints, leading to disability and reduced life expectancy. Synthetic glucocorticoids have a rapid anti-inflammatory effect and are commonly used at RA treatment initiation in combination with disease-modifying antirheumatic drugs. Importantly, due to the incidence of adverse effects, international guidelines recommend that glucocorticoids be used at the lowest possible dose and for the shortest possible time in RA, with the goal of discontinuation within the first three months.

In this study, the authors evaluated for the first time the use of glucocorticoids in combination with one of the following three biological anti-rheumatic drugs: tocilizumab, abatacept or TNFi, in a multicentre, international, real-life cohort of 17,663 patients. They found that there was no significant difference in the glucocorticoid-sparing effect of these three antirheumatic drugs. Nevertheless, the median time to glucocorticoid withdrawal exceeded 2 years in all treatment groups, well beyond the recommended 3-month period. However, the duration of glucocorticoid treatment after initiation of a biologic was shorter every year. There was significant heterogeneity between countries in terms of initial glucocorticoid use and discontinuation.

Heterogeneity in the pharmacological retention of anti-rheumatic drugs has been explored previously and may be related to patient heterogeneity, socioeconomic factors, treatment accessibility and differences in standard practice between countries. However, this has not been assessed to date with glucocorticoids. The authors therefore recommend that physicians make every effort to lower the dose or even discontinue glucocorticoids when disease activity is low, to prevent side effects; and that specific studies on country-level differences in prescribing glucocorticoids are done to understand differences and help adapt national guidelines.

News