Abstract
Background
Rheumatoid arthritis (RA) guidelines highlight the importance of early treatment to reduce disease activity and prevent long term damage [1-4]. Infection risk must be considered when starting biologic therapy as infections account for significant morbidity and mortality in RA [5]. Tocilizumab and sarilumab are anti-interleukin-6 (IL-6) receptor antibodies also effective in treating RA symptoms and preventing progression of structural damage [6-9]. Risk of infections in RA patients treated with IL-6 inhibitors have also been reported [10]. However, IL-6 inhibitor monotherapy has a superior efficacy than adalimumab [11]. More information is required to assess real-life burden and predict infection risk in RA patients using biologics [12].
Objectives
Examine the treatment pathway, factors associated with drug initiation and treatment discontinuation in patients with RA treated with either IL-6 inhibitors versus non-IL-6 biologic disease modifying anti-rheumatic drugs (bDMARDs).
Methods
A retrospective cohort study of RA patients in the Secure Anonymised Information Linkage databank, including primary care, secondary care and rheumatology clinic records of over 90% of the population in Wales, UK. Patients initiated on first treatment initiation, discontinuation and clinical outcomes including infection and hospitalisation were analysed using cox regression analysis.
Results
Data from 4922 patients with RA were analysed. The majority of patients had taken at least one conventional synthetic disease modifying anti-rheumatic drug (csDMARD) 95.7%, (4,691/4,922) while 29.6% (1,457) went on to take bDMARDs. Of these, 2% (97) biologic-naïve patients were treated with IL-6 inhibitors. Earlier treatment with bDMARDs was associated with increasing disease duration (HR: 1.11, 95% CI: 1.07 to 1.15) while younger age at diagnosis, orthopaedic surgery pre-treatment and kidney disease reduced the likelihood of being treated with biologics. Previous history of infection was associated with increased likelihood of treatment with IL-6 inhibitors rather than non-IL-6 bDMARDs (HR: 1.73, 95% CI: 1.15 to 2.59). The rate of treatment discontinuation was significantly higher in the non-IL-6 bDMARDs-treated patients compared to the IL-6 inhibitor treated individuals (difference: 9.4, 95% CI: 1.1 to 15.7). Treatment failure, orthopaedic surgery pre-treatment and steroid use was associated with non-IL-6 bDMARDs treatment failure (HR: 1.64, 95% CI: 1.00 to 2.68; HR: 1.62, 95% CI: 1.26 to 2.08, respectively). No factors were associated with treatment failure in the IL-6 inhibitor treated patients.
Conclusion
Patients treated with IL-6 inhibitors and other biologics were similar in demographics but had a different comorbidities pre- treatment; there was more orthopaedic surgery in those who went on to be treated with non-IL-6 biologics and more prior history of infections and kidney disease in those treated with IL-6 inhibitors. Treatment failure was higher in the non-IL-6 bDMARDs-treated patients.
Rheumatoid arthritis (RA) guidelines highlight the importance of early treatment to reduce disease activity and prevent long term damage [1-4]. Infection risk must be considered when starting biologic therapy as infections account for significant morbidity and mortality in RA [5]. Tocilizumab and sarilumab are anti-interleukin-6 (IL-6) receptor antibodies also effective in treating RA symptoms and preventing progression of structural damage [6-9]. Risk of infections in RA patients treated with IL-6 inhibitors have also been reported [10]. However, IL-6 inhibitor monotherapy has a superior efficacy than adalimumab [11]. More information is required to assess real-life burden and predict infection risk in RA patients using biologics [12].
Objectives
Examine the treatment pathway, factors associated with drug initiation and treatment discontinuation in patients with RA treated with either IL-6 inhibitors versus non-IL-6 biologic disease modifying anti-rheumatic drugs (bDMARDs).
Methods
A retrospective cohort study of RA patients in the Secure Anonymised Information Linkage databank, including primary care, secondary care and rheumatology clinic records of over 90% of the population in Wales, UK. Patients initiated on first treatment initiation, discontinuation and clinical outcomes including infection and hospitalisation were analysed using cox regression analysis.
Results
Data from 4922 patients with RA were analysed. The majority of patients had taken at least one conventional synthetic disease modifying anti-rheumatic drug (csDMARD) 95.7%, (4,691/4,922) while 29.6% (1,457) went on to take bDMARDs. Of these, 2% (97) biologic-naïve patients were treated with IL-6 inhibitors. Earlier treatment with bDMARDs was associated with increasing disease duration (HR: 1.11, 95% CI: 1.07 to 1.15) while younger age at diagnosis, orthopaedic surgery pre-treatment and kidney disease reduced the likelihood of being treated with biologics. Previous history of infection was associated with increased likelihood of treatment with IL-6 inhibitors rather than non-IL-6 bDMARDs (HR: 1.73, 95% CI: 1.15 to 2.59). The rate of treatment discontinuation was significantly higher in the non-IL-6 bDMARDs-treated patients compared to the IL-6 inhibitor treated individuals (difference: 9.4, 95% CI: 1.1 to 15.7). Treatment failure, orthopaedic surgery pre-treatment and steroid use was associated with non-IL-6 bDMARDs treatment failure (HR: 1.64, 95% CI: 1.00 to 2.68; HR: 1.62, 95% CI: 1.26 to 2.08, respectively). No factors were associated with treatment failure in the IL-6 inhibitor treated patients.
Conclusion
Patients treated with IL-6 inhibitors and other biologics were similar in demographics but had a different comorbidities pre- treatment; there was more orthopaedic surgery in those who went on to be treated with non-IL-6 biologics and more prior history of infections and kidney disease in those treated with IL-6 inhibitors. Treatment failure was higher in the non-IL-6 bDMARDs-treated patients.
| Original language | English |
|---|---|
| Pages (from-to) | 1384-1385 |
| Journal | Annals of the Rheumatic Diseases |
| Volume | 82 |
| Issue number | Supplement 1 |
| DOIs | |
| Publication status | Published - 30 May 2023 |