Investigators note similar efficacy and safety profiles in real-life study of reference and biosimilar forms of rituximab.
Two new publications provide evidence that the rituximab biosimilar CT-P10 (Truxima; Celltrion) could lower costs and expand patient access to biologic therapy for primary Sjögren syndrome (pSS)1 and an expert opinion that CT-P10 is a useful alternative to its reference product for treatment of rheumatoid arthritis.2
CT-P10, the first biosimilar to reference product rituximab (Rituxan, MabThera; Roche) to be marketed in the United States, is approved for treatment of non-Hodgkin lymphoma in the United States and all indications of rituximab in the European Union.
CT-P10 in pSS
In a retrospective analysis, investigators compared the rituximab originator with CT-P10 in a real-life setting in patients with pSS, a mucosal disease with various extraglandular manifestations. In 5% of patients, pSS evolves into B-cell lymphoma. Investigators noted that rituximab has been used off-label to treat pSS for 2 decades.
The authors discussed the significant role of B lymphocytes in the pathogenesis of pSS, noting that rituximab targets CD20, a B-cell surface receptor, and induces cell death. Rituximab has value in B-cell depletion therapy designed to eliminate malignant cells.
As of yet, rituximab for pSS has been evaluated in 4 randomized controlled trials (RCTs), plus prospective and case-control studies, and according to the authors, the majority of studies showed improvement in at least 1 outcome, such as disease activity scores, prednisone reduction, or organ-specific response. Most studies showed that rituximab reduced B lymphocyte numbers and activity. However, they said, “the clinical efficacy of B-cell depletion therapy with [rituximab] in pSS remains controversial” and the evidence from randomized control trials “is weak.”
An analysis of data from a separate trial of anti–B-cell therapy in patients with PSS concluded rituximab is not cost-effective for treating pSS. Therefore, guidelines for treating pSS suggest “the use of [rituximab] should be reserved to selected patients with severe, refractory systemic disease.” In light of the high cost of treatment, the authors argued that CT-P10 could be a safe and cost-effective alternative to the reference product and improve access for patients with pSS who have severe, refractory systemic disease.
In this small study in a real-life setting (N = 17), which included 9 patients in the rituximab originator group and 8 in the biosimilar group, the investigators performed a retrospective analysis of 48 weeks of clinical and laboratory data of patients with pSS from a tertiary rheumatology clinic. According to the authors, this is the first study comparing rituximab with its biosimilar in patients with pSS.
Similar disease activity and B lymphocyte numbers between groups
Baseline characteristics, including age, disease duration, and clinical and laboratory parameters, did not differ between groups. Overall, patients had moderate-to-high disease activity and disease duration of less than 5 years.
Measures of disease activity as assessed by clinicians improved significantly from baseline in both groups starting at week 24 and continuing through week 48. Minimal clinically important improvement (MCII) based on the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) and clinESSDAI (ESSDAI without biological domains) was attained by all patients by 48 weeks.
There was no significant improvement from baseline at any timepoint in patient-reported symptoms in either group, as assessed by the EULAR Sjögren's Syndrome Patient-Reported Index (ESSPRI). However, 6 of 8 patients in the CT-P10 group and all 9 patients in the originator group achieved MCII based on ESSPRI (a reduction of at least 1 point or 15% of the baseline value) by 48 weeks.
Similar depletion of CD19+ lymphocytes was reported in both groups.
The authors said safety profiles were similar. Four adverse events were recorded in 4 patients across the 12-month follow-up: 1 mild cutaneous reaction (originator group) and 3 upper airway infections (1 originator group, 2 biosimilar group) that required antibiotic therapy.
The authors said that “given the lack of studies on CT-P10 in pSS, [their investigation] provides important insight to clinicians who will be required to use this compound in pSS patients,” despite the small number of patients and retrospective nature of the study.
CT-P10 performance in RA reviewed
A review article in Expert Opinion on Drug Metabolism & Toxicology evaluated the pharmacokinetics, pharmacodynamics, toxicology, efficacy, and safety of CT-P10 in rheumatoid arthritis (RA). The authors provided an expert opinion, saying CT-P10 may be a “useful alternative for the treatment of RA in all indications for originator RTX.” They recommended more studies to investigate long-term effectiveness and safety of CT-P10 in real-world settings, as well as research into new indications for CT-P10 and effective ways to counteract the nocebo effect for all biosimilars. CT-P10 is currently approved for RA in the European Union but not in the United States.
1. Pavlych V, Di Muzio C, Alunno A, Carubbi F. Comparison of rituximab originator with CT-P10 biosimilar in patients with primary Sjögren's syndrome: a retrospective analysis in a real-life setting. Front Med. Published online September 8, 2020. doi:10.3389/fmed.2020.00534
2. Yoo DH, Suh CH, Shim SC, Lee SJ, Kim SH, Park W. A pharmacokinetic evaluation of the rituximab biosimilar CT-P10 in the treatment of rheumatoid arthritis. Expert Opin Drug Metab Toxicol. Published online October 5, 2020. doi: 10.1080/17425255.2020.1832082