POS0295 OCCURRENCE OF SERIOUS INFECTIONS IN RHEUMATOID ARTHRITIS PATIENTS CONCURRENTLY TREATED WITH A BIOLOGIC AGENT AND DENOSUMAB: A RETROSPECTIVE STUDY WITH PROPENSITY SCORE

Abstract

BackgroundDenosumab is a monoclonal antibody used in patients with osteoporosis. It inhibits the receptor activator NF-kB ligand (RANKL), an essential cytokine mediator of osteoclastogenesis. Some concerns have been raised about Denosumab safety profile, especially when it is administered concurrently with biologic drugs for rheumatoid arthritis (RA) (1,2). Indeed, RANK and RANKL have a known immunomodulatory effect (2). In a retrospective study, Lau et al. (1) showed that patients concurrently treated with Denosumab and biologic disease modifying anti-rheumatic drugs (bDMARDs) had a higher rate of serious infections compared to patients taking bDMARDs only, but no adjustment was made for any observed imbalances in potential confounders, such as age and disease activity, between the groups.ObjectivesThis study aims to evaluate, in a monocentric cohort of RA patients concurrently treated with bDMARDs and Denosumab, the safety of such combination.MethodsWe retrospectively observed RA patients on bDMARDs ± methotrexate and denosumab (DEN group) for comorbid osteoporosis and RA patients treated with bDMARDs±methotrexate (noDEN group) who started treatment in a tertiary care centre from 2015 to 2020. Clinical characteristics were gathered at baseline and at 12-month follow up. We also recorded the occurrence of serious infections between groups (defined as infections requiring hospitalization and/or parenteral antibiotics). We deployed the nearest-neighbour matching algorithm (1:4), based on Propensity Score (PS), in order to adjust for non-randomization. The McNemar’s test was used to compare the frequency of serious infection in the two groups.ResultsDEN group consisted of 36 patients were recruited, while the cohort of patients in noDEN group consisted of 547 individuals (Table 1). After PS matching only 58 patients were noDEN group, matched for disease duration, presence/absence of ACPA antibodies, baseline BMI, baseline DAS28 and daily prednisone dosage. In the matched cohort, we found an increase in terms of frequency of serious infections in DEN group, even if not statistically significant (Figure 1). All the infections were completely resolved after hospitalization and/or parenteral antibiotic treatment, without fatal events or irreversible complications. Both groups were not stratified for bDMARDs mechanism of action (MoA). Of note, in the DEN group Rituximab therapy was admnistered in 22% of patients, while in noDEN group in 12% of them.Table 1.Patients’ characteristics at baseline.Av. Obs.bDMARDs OnlyAv. Obs.bDMARDs + DenosumabFemale, n (%)547466 (85.2%)3834 (89.4%)Age, y (mean±sd)54753.3±13.23863.4±11.1Disease duration, m (mean±sd)472120.2±105.338207.9±126.5DAS28, n(mean±sd)5324.55±1.39382.90±1.44PCR, mg/dL (mean±sd)5391.77±4.51380.81±1.22HAQ, n (mean±sd)5161.28±0.86381.54±0.87ACPA, n. (%)541416 (76.8%)3817 (44.7%)Figure 1.Occurrence of serious infections at 12-months follow-up.ConclusionThe occurrence of serious infections among RA patients receiving denosumab in combination with bDMARDs ± MTX for RA was not significantly increased compared to those receiving bDMARDs ± MTX alone at 12 months from treatment baseline. Further studies powered for detecting difference between bDMARDs MoA are necessary in order to assess the infection risk of denosumab co-administration.