In the first real-world study on effectiveness of the rituximab biosimilar GP2013 (Rixathon; Sandoz) in rheumatoid arthritis (RA), both rituximab-naïve patients and those who underwent a mandatory switch in Norway had “satisfactory” treatment responses and drug retention rates. Over 2 years of follow-up, switched patients had “no deterioration in disease activity outcomes” and outcomes improved in rituximab-naïve patients.

Data on effectiveness of switching from the reference rituximab (MabThera) to a biosimilar in real-world clinical practice are “sparse,” according to the authors, who cited only 1 previous real-world study on drug retention rates. They said this lack of data may raise concerns about switching for both patients and physicians and contribute to the nocebo effect.

Rituximab is a chimeric monoclonal antibody targeting CD20, an antigen on the surface of B cells, used to treat moderate-to-severe RA in patients who have an inadequate response or intolerance to conventional synthetic disease-modifying anti-rheumatic drugs, such as methotrexate. Following the endorsement of biosimilar use in RA by the European League Against Rheumatism, Norway instituted a policy of mandatory nonmedical switching from the rituximab originator to biosimilars and starting new patients on biosimilars to reduce costs.

The retrospective observational cohort study included 110 patients of an RA outpatient clinic in Norway who were treated with GP2013. Of these patients, 88 were switched from the reference product and 22 were rituximab-naïve and began therapy with the biosimilar. Disease activity and patient-reported outcomes (PROs) were assessed from 1 year prior to baseline to 2 years of biosimilar therapy.

There were differences in patient characteristics between groups: Disease duration was longer for switched patients (14 years vs 3 years). More patients in the switched group were currently using steroids (68% vs 35%). Most (91%) rituximab-naïve patients received 2000 mg GP2013 in their first cycle, whereas 85% of switched patients received 1000 mg or 500 mg. Also, the authors commented, “as expected, all disease activity measures were significantly higher in [rituximab-naïve] patients.”

In the patients who were switched from the reference product, all disease activity measures other than PROs were maintained throughout the 2-year follow-up. Patient global assessment (PGA) and clinical disease activity index (CDAI), which includes PGA, increased significantly from baseline to 2 years.

According to the investigators, these measures “are often meant to represent the subjective component when obtaining RA disease activity,” and a number of potential contributing factors such as noninflammatory pain components, psychosocial factors, and comorbidities should be considered when interpreting these PROs. They added, “a phenomenon of either not achieving or misestimating RA remission targets solely due to the high PGA is well-known and remains the subject of lively debate.”

In the rituximab-naïve group, significant improvements in most disease activity measures including PROs were achieved during the first year of treatment and maintained at 2 years. At 1-year, significant improvements were reported for erythrocyte sedimentation rate (ESR), 28 swollen joint count (SJC28), 28 tender joint count (TJC28), disease activity score (DAS) with 28 joint counts with ESR, DAS with 28 joint counts with C-reactive protein (CRP), CDAI, PGA, and investigator global assessment. Improvement in CRP was not significant at one or 2 years. The drug retention rate was significantly higher in the switched group compared to the naïve group at 1 year (84% vs 64%) and 2 years (60% vs 49%).

The investigators concluded that patients with RA who were treated with GP2013 had a treatment response and drug retention rate in the real-world setting that supports the equivalence of GP2013 to the reference rituximab. They discussed limitations of their study, including those typical to observational studies, such as “a certain level of missing data, confounding factors and attrition bias,” the lack of safety data, and the small number of patients in the rituximab-naïve group. However, they said these limitations were “somewhat balanced” by the long follow-up period, real-world setting, and number of outcome measures monitored.

Source:- Center For Biosimilars