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AB0208 (2021)
DO LOW CONCENTRATIONS OF CITRATE IN AN ADALIMUMAB FORMULATION IMPACT THE INCIDENCE AND/OR INTENSITY OF INJECTION SITE PAIN? DATA FROM PHASE I AND III STUDIES ASSESSING THE LOCAL TOLERANCE OF GP2017 (ADALIMUMAB BIOSIMILAR, SDZ-ADL) IN HEALTHY VOLUNTEERS, RHEUMATOID ARTHRITIS, AND PSORIASIS PATIENTS
P. Wiland1, A. Blauvelt2, L. Lemke3, O. Von Richter3, A. Balfour4, F. Furlan5, N. Gaylis6
1Medical University, Department of Rheumatology and Internal Medicine, Wroclaw, Poland
2Oregon Medical Research Center, Research Excellence & Personalized Patient Care, Portland, United States of America
3Hexal AG (A Sandoz company), Clinical Development Biopharmaceuticals, Holzkirchen, Germany
4Hexal AG (A Sandoz company), Clinical Development Biostatistics, Holzkirchen, Germany
5Hexal AG (A Sandoz company), Global Medical Affairs, Holzkirchen, Germany
6Arthritis and Rheumatic Disease Specialties, 21097 NE 27th Court Suite 200, Aventura, United States of America

Background: Adalimumab (ADL) is typically self-administered every 2 weeks (W) as a subcutaneous (s.c.) injection by patients (pts) for diverse indications, including rheumatoid arthritis (RA), psoriatic arthritis (PsA), and psoriasis (PsO). Conflicting evaluations of local tolerance to formulations containing citrate buffer have created insecurities among health care professionals and pts. 1,2


Objectives: To evaluate local tolerance of SDZ-ADL (GP2017), a biosimilar ADL with low citrate concentration (1.2 mM), 3 in 466 healthy volunteers (HV) and 408 pts (RA: 177 and PsO: 231 including PsA: 52) from four phase I pharmacokinetic (PK) and two phase III confirmatory studies.


Methods: HV evaluated their injection site pain (ISP) using a Visual Analogue Scale (VAS) of 0–100 mm. HV received a single 40 mg/0.8 mL s.c. injection and pts received SDZ-ADL every 2W during 48–51W duration of study. Injection site reactions (ISR) as well as adverse events (AEs) were assessed by investigators during the clinical studies. Details of study designs have been reported previously. 4–7


Results: Overall, 456 (97.9%) HV experienced no ISR. Ten HV experienced ISR. These were mostly of mild intensity; only 1 (0.2%) had an ISR of moderate intensity. 96.6% of HV experienced no pain (VAS score 0–4 mm) 8 at 1-hour post-dose ( Figure 1 ). In the phase III studies, a low number of ISR/ISP events were observed, which decreased during the course of study. Detailed results are provided in Table 1 . No ISR/ISP led to treatment or study discontinuation in any study.


Conclusion: The proportion of HV and pts experiencing ISR and ISP after administration of SDZ-ADL was low, with no events leading to treatment or study discontinuation. These results call into question the clinical impact of citrate and its concentration in ADL formulations on the incidence and intensity of ISP.


REFERENCES:

[1]Nash et al. Rheumatol Ther . 2016;3:257–70.

[2]NHS. Regional medicines optimisation committee briefing, best value biologicals: adalimumab update 6. July 2019. https://www.sps.nhs.uk/wp-content/uploads/2019/07/Adalimumab-RMOC-Briefing-6.pdf .

[3] https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761071lbl.pdf .

[4]Blauvelt A, et al. Br J Dermatol . 2018;179:623–31.

[5]Wiland P, et al. BioDrugs 2020;34:809–23.

[6]Richter OV, et al. Expert Opin Biol Ther . 2019;19:1057–64.

[7]Richter OV, et al. Expert Opin Biol Ther . 2019;19:1075–83.

[8]Hawker GA, et al. Arthritis Care Res . 2011;63:240–52.

Proportion of HV with ISP in phase I PK studies

ISP and ISR results from phase I PK and phase III confirmatory studies

Phase I PK studies
Study 101 (N=73 ) 102 (N=108 ) 103 (N=178 ) 104 (N=107 ) Pooled studies (N=466 )
VAS scores (mm) at 1-hour post-dose
Mean (SD) 0.89 (2.07) 0.07 (0.52) 1.03 (1.71) 1.03 (2.49) 0.79 (1.84)
Median 0 0 1 0 0
ISR scores at 1-hour post-dose, n (% )
None 73 (100) 106 (98.2) 178 (100) 99 (92.5) 456 (97.9)
Mild 0 (0) 1 (0.9) 0 (0) 8 (7.5) 9 (1.9)
Moderate 0 (0) 1 (0.9) 0 (0) 0 (0) 1 (0.2)
Phase III confirmatory studies
ADACCESS 5 * (PsO and PsA pts ) ADMYRA 6 * (RA pts )
W0–17 (N=231) W0–51 (N=168; including pts re-randomised to continue SDZ-ADL after W17) W0–24 (N=177) W0–48 (N=177; all pts continued SDZ-ADL after W24)
Dosage Induction 80 mg W0, then 40 mg EoW s.c. 40 mg EoW s.c. 40 mg EoW s.c. 40 mg EoW s.c.
Study duration, W 17 51 24 48
AEs - ISR, n (%), events 15 (6.5), 34 9 (5.4), 26 7 (4.0), 11 7 (4.0), 12
Mild 14 (6.1), 30 9 (5.4), 26 7 (4.0), 11 7 (4.0), 12
Moderate 1 (0.4), 4 0 0 0
AEs - ISP (reported as ISR), n (% ) 3 (1.3) 1 (0.6) 2 (1.1) 2 (1.1)

*ADACCESS and ADMYRA were switch studies, therefore, only pts exposed to SDZ-ADL throughout the study period are included here. EoW, every other week, N, number of HV or pts


Disclosure of Interests: Piotr Wiland Speakers bureau: Celltrion, Celgene, Eli Lilly, Novartis, Pfizer, Sandoz, Sanofi-Aventis, Consultant of: Celltrion, Celgene, Eli Lilly, Novartis, Pfizer, Sandoz, Sanofi-Aventis, Andrew Blauvelt Speakers bureau: AbbVie, Almirall, Arena, Athenex, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant, Eli Lilly and Company, Evommune, Forte, Galderma, Incyte, Janssen, Leo, Novartis, Pfizer, Rapt, Regeneron, Sandoz, Sanofi Genzyme, Sun Pharma, and UCB Pharma., Consultant of: AbbVie, Almirall, Arena, Athenex, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant, Eli Lilly and Company, Evommune, Forte, Galderma, Incyte, Janssen, Leo, Novartis, Pfizer, Rapt, Regeneron, Sandoz, Sanofi Genzyme, Sun Pharma, and UCB Pharma., Lena Lemke Employee of: Hexal AG, Oliver von Richter Employee of: Hexal AG, Alison Balfour Employee of: Hexal AG, Fabricio Furlan Employee of: Hexal AG, Norman Gaylis: None declared

Citation: Ann Rheum Dis, volume 80, supplement 1, year 2021, page 1130
Session: Rheumatoid arthritis - biological DMARDs (Publication Only)