TOPIC SERIES: BIOSIMILAR DRUGS

Therapeutically switching patients with ankylosing spondylitis (AS) from infliximab reference product (RP) to its biosimilar CT-P13 was not associated with negative effects, according to research published in Annals of Rheumatic Disease.

A biosimilar is defined by the World Health Organization as a “biotherapeutic product which is similar in terms of quality, safety and efficacy to an already licensed RP”. CT-P13 has the same amino acid sequence as infliximab.


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Both the U.S. Food and Drug Administration and the European Medicines Agency have voted to recommend approval of CT-P13 for all indications for which the infliximab RP has already been approved. 


To evaluate the safety and efficacy of switching patients with AS from the infliximab RP to CT-P13, Won Park, MD, from In-Ha University School of Medicine, Incheon, Republic of Korea, and colleagues recruited patients with active AS who had already completed a 54-week randomized CT-P13 efficacy study (ClinicalTrials.gov identifier NCT01220518) to an open-label, single-arm, 1-year extension study where CT-P13 was intravenously administered every 8 weeks from week 62 to week 102 (ClinicalTrials.gov Identifier NCT01571206).

Study participants in the initial phase 1 trial had active AS for ≥3 months according to the 1984 modified New York classification criteria. They received 9 intravenous infusions of CT-P13 (5 mg/kg)  or the infliximab RP over the course of the 54-week trial.  These participants were given the option of continued participation in the extension study, where both patients and physicians were blinded to the initial treatment received during the initial 54-weeks. Patients who chose to continue were given an additional 6 infusions of CT-P13 every 8 weeks, from week 62 through week 102. 

Researchers defined the efficacy endpoints as the proportions of patients achieving clinical response according to the following criteria: Assessment of SpondyloArthritis international Society (ASAS)20, ASAS40, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Metrology Index, and the Ankylosing Spondylitis Disease Activity Score (ASDAS)-C reactive protein (CRP).

Immunology assessments were conducted at baseline and weeks 14, 30, 54, 78, and 102 to determine the proportion of patients who had antidrug antibodies. Treatment-emergent adverse events were continually assessed throughout both the initial and extension studies.

Eighty eight patients from the initial study were maintained on CT-P13 therapy (defined as the “maintenance group”) while 86 patients were switched to CT-P13 from the infliximab RP (defined as the “switch group).    

At week 102 (48 weeks after the last infusion of infliximab RP per the initial study at week 54), ASAS20 response rates in the maintenance and switch groups were 80.7% and 76.9%, respectively.  ASAS40 response rates in the maintenance and switch groups were 63.9% and 58.0% respectively. 

ADA positivity rates were similar in both the maintenance and switch groups at week 102 (23.3% vs 27.4%). In the extension time period, CT-P13 displayed a long-term safety profile consistent with initial studies evaluating the infliximab RP.

“Data for all other efficacy end points were also similar between the maintenance and switch groups throughout the main and extension study periods, as well as within each group over both study periods,” the authors stated.

Summary and Clinical Applicability

Switching patients with active AS from infliximab reference product (RP) to its biosimilar CT-P13 was not associated with negative effects in patients with ankylosing spondylitis.

“The current data suggest that switching to CT-P13 in patients previously treated with the infliximab RP shows similar efficacy and safety profiles, compared with maintaining CT-P13,” the authors concluded.

Limitations and Disclosures

This single-arm, open-label extension study was not statistically powered to evaluate CT-P13 non-inferiority to infliximab RP.  Long-term data from the pharmacovigilance program started by Celltrion will monitor the continued safety of CT-P13 use.

This study was funded by CT-P13 manufacturer CELLTRION Inc. 

Reference

Park W, Yoo DH, Miranda P, et al. Efficacy and safety of switching from reference infliximab to CT-P13 compared with maintenance of CT-P13 in ankylosing spondylitis: 102-week data from the PLANETAS extension study. Ann Rheum Dis. E-pub ahead of print April 26, 2016  doi: 10.1136/annrheumdis-2015-208783