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Randomized Controlled Trial
. 2024 Nov 17;14(11):e081687.
doi: 10.1136/bmjopen-2023-081687.

Immunogenicity of adalimumab reference product and adalimumab-adbm in patients with rheumatoid arthritis, Crohn's disease and chronic plaque psoriasis: a pooled analysis of the VOLTAIRE trials

Vibeke Strand  1 , Dorothy McCabe  2 , Shaun Bender  2   3
Affiliations
Randomized Controlled Trial

Immunogenicity of adalimumab reference product and adalimumab-adbm in patients with rheumatoid arthritis, Crohn's disease and chronic plaque psoriasis: a pooled analysis of the VOLTAIRE trials

Vibeke Strand et al. BMJ Open. .

Abstract

Objective: This post hoc analysis compared the immunogenicity of the biosimilar adalimumab-adbm (Cyltezo) with the adalimumab reference product (RP; Humira) across indications, including rheumatoid arthritis (RA), Crohn's disease (CD) and plaque psoriasis (PsO), and by patient sex in the VOLTAIRE trials programme.

Methods: In each active-comparator randomised controlled trial (RCT), immunogenicity was assessed at various time points by the proportion of patients with antidrug antibodies (ADAs) and neutralising antibodies (nAbs), using acid dissociation followed by electrochemiluminescence assay. Assay sensitivity was 50 ng/mL, and drug tolerance was ≥30 µg/mL (free drug) at the low positive control level.

Results: Minor differences in immunogenicity parameters (ADAs, ADA titres and nAbs) were evident between adalimumab-adbm and adalimumab RP across these three immune-mediated inflammatory diseases (IMIDs). The proportion of ADA-positive and nAb-positive patients increased from baseline over time in all three RCTs, as expected, and was similar in the RA and CD RCTs but with higher numbers of ADA-positive and nAb-positive patients reported in the PsO trial. Subgroup analysis by patient sex showed the same trend.

Conclusions: Differences among the RCTs may partially be explained by concomitant background therapy (methotrexate) in the RA trial, stable doses of azathioprine, 6-mercaptopurine or methotrexate in 36% of patients with CD and absence of background therapy in the PsO RCT. The analyses further confirm the biosimilarity of adalimumab-adbm with the adalimumab RP across IMIDs and provide supporting evidence that adalimumab-adbm is an interchangeable biosimilar with consistent clinical results in patients originally treated with the RP.

Trial registration numbers: VOLTAIRE-RA (NCT02137226; EudraCT 2012-002945-40); VOLTAIRE-CD (NCT02871635; EudraCT 2016-000612-14); VOLTAIRE-PsO (NCT02850965; EudraCT 2016-000613-79).

Keywords: chronic disease; inflammatory bowel disease; psoriasis; rheumatology.

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Conflict of interest statement

Competing interests: VS reports consulting for AbbVie, Amgen, Aria, AstraZeneca, Bayer, Bioventus, BlackRock, BMS, Boehringer Ingelheim, Celltrion, ChemoCentryx, Equillium, Gilead, Genentech/Roche, Glenmark, GSK, Horizon, Inmedix, Janssen, Kiniksa, Kypha, Lilly, Merck, MiMedx, Novartis, Pfizer, Priovant, Regeneron, Rheos, R-Pharma, Samsung, Sandoz, Sanofi, Scipher, Setpoint, Sorrento, Spherix and Tonix. SB reports previous employment by Boehringer Ingelheim Pharmaceuticals. DM reports previous employment by Boehringer Ingelheim Pharmaceuticals.

Figures

Figure 1
Figure 1. Time course of ADA development in (A) VOLTAIRE-RA, (B) VOLTAIRE-CD and (C) VOLTAIRE-PsO (safety analysis sets). ADA, antidrug antibody; CD, Crohn’s disease; PsO, plaque psoriasis; RA, rheumatoid arthritis; RP, reference product.
Figure 2
Figure 2. Time course of nAb development in (A) VOLTAIRE-RA, (B) VOLTAIRE-CD and (C) VOLTAIRE-PsO RCTs (safety analysis sets). CD, Crohn’s disease; nAb, neutralising antibody; PsO, plaque psoriasis; RA, rheumatoid arthritis; RCT, randomised controlled trial; RP, reference product.
Figure 3
Figure 3. Frequency of patients meeting primary clinical response criteria per treatment arm stratified by ADA titre positivity (safety analysis sets) for VOLTAIRE-RA, VOLTAIRE-CD and VOLTAIRE-PsO RCTs. ACR20, American College of Rheumatology 20% response criteria; ADA, antidrug antibody; CD, Crohn’s disease; CDAI, Crohn’s Disease Activity Index; PASI, Psoriasis Area and Severity Index; PASI 50 / PASI 75, 50% or 75% reduction in PASI, respectively; PsO, plaque psoriasis; RA, rheumatoid arthritis; RCT, randomised controlled trial; RP, reference product.
Figure 4
Figure 4. Frequency of patients meeting primary clinical response criteria per treatment arm stratified by nAb titre positivity (safety analysis sets) for VOLTAIRE-RA, VOLTAIRE-CD and VOLTAIRE-PsO RCTs. ACR20, American College of Rheumatology 20% response criteria; CD, Crohn’s disease; CDAI, Crohn’s Disease Activity Index; nAb, neutralising antibody; PASI, Psoriasis Area and Severity Index; PASI 50 / PASI 75, 50% or 75% reduction in PASI, respectively; RCT, randomised controlled trial; RA, rheumatoid arthritis; RCT, randomised controlled trial; RP, reference product.
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References

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