Long-Term Effects of Rituximab vs TNFis in RA-Associated Bronchiectasis

The majority of patients with rheumatoid arthritis (RA)-associated bronchiectasis treated with rituximab have a satisfactory safety profile, with either stable or improved pulmonary symptoms over a 10-year follow-up, according to findings published in Rheumatology. Researchers also found that discontinuation rates due to adverse lung outcomes were better with rituximab than those in a matched cohort of patients treated with tumor necrosis factor inhibitors (TNFis).

To evaluate the effects of rituximab on RA-associated bronchiectasis and compare 5-year respiratory survival rates between patients treated with rituximab and those treated with TNFis, investigators conducted a retrospective longitudinal cohort study of consecutive adult patients with RA-associated bronchiectasis from 2 medical centers in the United Kingdom over 10 years. Respiratory survival was defined as the time from initiation of therapy to discontinuation due to lung exacerbation or to respiratory-related death.

Of the 800 individuals with RA who received rituximab, 68 had RA-associated bronchiectasis (8.5%). The median duration (interquartile range) of response for cycles 1 through 3 were 54 weeks (46-68 weeks), 50 weeks (40-64 weeks), and 52 weeks (46-60 weeks), respectively. Before cycle 1 of rituximab, 22 of these 68 patients had either inadequate response or intolerance to TNFis.

At 12 months after the first cycle of rituximab, 31% of patients had fewer exacerbations than in the year prior to therapy, 53% remained stable, and 16% had increased exacerbations. No significant difference was seen in the median number of infective exacerbations before and after the initial cycle of rituximab (P =.105). Exacerbation rates improved after treatment cycle 2 and stabilized up to 5 cycles. Of the 60 patients who received ≥2 cycles of rituximab, 7 (12%) experienced an increased number of exacerbations; these were associated with secondary hypogammaglobulinemia (n=5), aspergillosis (n=3), and concurrent alpha-1-antitrypsin deficiency (n=1).

Among the 68 patients with RA-associated bronchiectasis who received rituximab, 11.8% discontinued treatment due to lung exacerbation (n=3) or lung infection-related death (n=5). Among the 46 TNFi-treated patients with RA-associated bronchiectasis, 32.6% discontinued treatment due to lung exacerbations (n=13) or lung infection–related death (n=2). Death rates due to respiratory causes were similar between the groups (7.4% for the rituximab-treated group vs 4.3% for the TNFi-treated group). After adjusting for age, sex, and center effect, a significantly better rate of 5-year respiratory survival was seen in rituximab-treated patients compared with TNFi-treated patients (hazard ratio, 0.40; 95% CI, 0.17-0.96; P =.041).

Study investigators concluded that “because most patients with [RA-associated bronchiectasis] had stable or improved lung exacerbations during [rituximab] therapy as well as better 5-year respiratory survival against a matched TNFi cohort, our findings offer reassurance that [rituximab] is an acceptable treatment choice for [patients with RA-associated bronchiectasis and] severe arthritis, who require treatment with a biologic. These data also support a definitive study of [rituximab] for the management of [RA-associated bronchiectasis] from both an articular and a respiratory perspective.”

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

Reference

Md Yusof MY, Iqbal K, Darby M, et al. Effect of rituximab or tumour necrosis factor inhibitors on lung infection and survival in rheumatoid arthritis-associated bronchiectasis [published online February 17, 2020]. Rheumatology (Oxford). doi:10.1093/rheumatology/kez676