Multiple switching between the biosimilar adalimumab PF-06410293 and reference adalimumab in patients with active rheumatoid arthritis: a phase 3, open-label, randomised, parallel-group study.

BACKGROUND

An adalimumab biosimilar with an interchangeability designation could increase access to effective treatment for more patients. We aimed to assess the interchangeability of adalimumab biosimilar PF-06410293 (adalimumab-afzb) and reference adalimumab using a multi-switch study design.

METHODS

We did an open-label, randomised, parallel-group study at 61 community (n=29), hospital (n=12), and academic (n=20) sites in ten countries (Bulgaria, Bosnia and Herzegovina, Czech Republic, Lithuania, Poland, Russia, Serbia, South Africa, Ukraine, and USA). Eligible patients were aged 18-70 years and met the 2010 American College of Rheumatology-European League Against Rheumatism classification criteria for rheumatoid arthritis for at least 4 months with moderately to severely active rheumatoid arthritis, based on their physician's evaluation. Eligible patients had been receiving methotrexate for at least 12 weeks and been on a stable dose for at least 4 weeks before the first dose of study medication. All patients received subcutaneous reference adalimumab (40 mg/0·4 mL [100 mg/mL] every 2 weeks) for 10 weeks before randomisation. At week 10, patients were randomly assigned (1:1) to either three switches between subcutaneous reference adalimumab (40 mg/0·4 mL [100 mg/mL] every 2 weeks) and adalimumab-afzb (40 mg/0·8 mL [50 mg/mL] every 2 weeks; switching group), or continuous dosing with subcutanous reference adalimumab (40 mg/0·4 mL [100 mg/mL] every 2 weeks; non-switching group) with stratification by bodyweight groups. Patients, investigators, and site personnel were not masked to treatment allocation. Primary endpoints were maximum observed serum concentration (C

FINDINGS

Of the 569 patients assessed for eligibility between Jan 13, 2020, and June 22, 2021, 445 were enrolled, and 427 completed the first 10 weeks and were randomly assigned (213 to the switching group and 214 to the non-switching group). Participants had a median age of 56 years (IQR 46-63), 354 (83%) of 427 patients were women and 73 (17%) were men, and 422 (99%) were White. In the pharmacokinetic population (n=380), no clinically meaningful differences were observed in mean steady-state pharmacokinetic parameters between the switching and non-switching groups (geometric mean AUC 2237 μg × h/mL in the switching group and 2125 μg × h/mL in the non-switching group; C

INTERPRETATION

The risk of multiple switches between reference adalimumab and adalimumab-afzb with respect to diminished efficacy (using pharmacokinetics as a surrogate) or safety is not greater than the risk of using reference adalimumab alone.

FUNDING

Pfizer. VIDEO ABSTRACT.

Informations de copyright

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Déclaration de conflit d'intérêts

Declaration of interests DFA, DSC, CC, CAI, KW, and WZ are employees of Pfizer and hold stock or stock options in Pfizer. WZ holds stock or stock options in Abbott and AbbVie. RF reports clinical study support from AbbVie, Amgen, Arthrosi Therapeutics, AstraZeneca, Bristol-Myers Squibb, Eli Lilly and Company, Flexion Therapeutics, Galvani Bioelectronics, Genentech, Gilead Sciences, GSK, Horizon Pharmaceuticals, Janssen, Novartis, Pfizer, Selecta Biosciences, UCB, Viela Bio, Vorso, and consulting fees from AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly and Company, Gilead Sciences, GSK, Novartis, Pfizer, UCB, and VYNE Therapeutics. SL reports speaker fees from AbbVie. WS reports speaker fees from AbbVie, Amgen, Eli Lilly and Company, and Pfizer, and holds stock or stock options in Pfizer.