Information intended for healthcare professionals only.

This formulary decision guide was developed from content provided by Mylan Ltd in a format developed by Guidelines in Practice. It has been reviewed by a medicines management professional.

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Key points

  • FDG-Hulio (adalimumab biosimilar)

    Hulio is citrate free, delivered via a 29‑gauge stainless steel needle (with plastic cover), and presentations include a two-step auto-injector and a latex-free, pre-filled syringe with safety device
  • In a 2016 report, the EU Commission said: The availability of biosimilars… offers potential economic benefit to healthcare systems, while supporting patients’ access to new treatment options brought about by advances in medical science.1

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Drug name

Hulio®▼ (adalimumab biosimilar 40 mg)

Indications

  • Hulio is licensed for all indications associated with the adalimumab reference product
  • See the Summary of Product Characteristics for the list of indications: rheumatoid arthritis, juvenile idiopathic arthritis, axial spondyloarthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis, hidradenitis suppurativa, Crohn’s disease, ulcerative colitis, and uveitis.2

Dosage in adults

  • Treatment to be initiated by a specialist; adult doses for administration by subcutaneous injection for the three main indications:3
    • rheumatoid arthritis (RA)—40  mg every 2 weeks, then increased if necessary to 40 mg once weekly, dose to be increased only in patients receiving adalimumab alone, review treatment if no response within 12 weeks
    • Crohn’s disease—initially 80  mg, then 40 mg after 2 weeks; maintenance 40 mg every 2 weeks, increased if necessary to 40 mg once weekly, maximum 40 mg administered at a single site, review treatment if no response within 12 weeks of initial dose
    • plaque psoriasis—initially 80 mg, then 40 mg every 2 weeks, to be started 1 week after initial dose, review treatment if no response within 16 weeks
  • See the Summary of Product Characteristics2 for additional dosage information.

Delivery

  • Hulio is citrate free, delivered via a 29-gauge stainless steel needle (with plastic cover), and presentations include a two-step auto-injector and a latex-free, pre-filled syringe with safety device.

Biosimilars

  • The revised position paper on biosimilar medicines from the National Rheumatoid Arthritis Society in 2017 states that:4
    • the designation of a biological drug as a ‘biosimilar’ by a regulatory authority demands that extremely rigorous quality controls are met with respect to characterisation of the biosimilar in relation to the originator drug, which can give a great deal of confidence to patients
    • these quality controls for the biosimilar are much more stringent than those required for originators in the early days of biological disease-modifying anti-rheumatic drugs
  • NICE Key therapeutic topic (KTT15) recommends ensuring that all biological medicines, including biosimilar medicines, are prescribed by brand name so that products cannot be automatically substituted at the point of dispensing.5

Evidence for use­—efficacy

  • The ARABESC randomised, double-blind, active-controlled study compared the efficacy and safety of an adalimumab biosimilar (Hulio; FKB327) with the adalimumab reference product (RP; ADL) in patients with RA inadequately controlled on methotrexate:
    • Hulio met the primary study objective establishing equivalence with the RP
    • ACR20 (American College of Rheumatology definition of 20% improvement in a core set of measures) response rates over time overlapped during weeks 4–24.

ACR20 response rates (Hulio and adalimumab reference product)

Evidence for use­—safety

  • Evidence from the ARABESC study comparing Hulio and the adalimumab RP demonstrated:6
    • the proportions of patients reporting treatment-emergent adverse events (TEAEs) were similar (55.5% vs 61.6%)
    • adverse events were mainly mild or moderate; the most common TEAEs (≥5%) were nasopharyngitis (7.1% vs 8.0%), and upper respiratory tract infection (3.6% vs 5.0%)
    • incidences of serious adverse events were similar (4.1% vs 5.2%)
    • deaths from treatment-related disseminated tuberculosis (TB) were 1 vs 0, with higher reports of active TB in the RP group (1 vs 3); mean serum trough concentration-time profiles of the two groups were comparable
    • immunogenicity: prevalence and titres of antidrug antibodies were similar, including at final sampling (57.9% vs 55.8%).

Long-term safety evidence

  • The ARABESC study was continued with an open-label extension, called ARABESC-OLE, to compare Hulio with the adalimumab RP for long-term safety, efficacy, and immunogenicity in patients with RA.7 The study is completed and currently under evaluation, with results scheduled for publication in October 2018:7
    • at interim analysis, safety profiles were comparable for all treatment sequences, although group sizes were reduced after switching
    • ACR20 response rate at week 30 was comparable after continuous (Hulio‑Hulio, 82.5%; RP‑RP, 84.3%) and switched (Hulio‑RP, 86.5%; RP‑Hulio, 89.1%) treatment
    • no consistent differences in pharmacokinetics and anti-drug antibody profiles were seen between continuous and switched treatments.

ARABESC study

Cost saving

  • NHS England’s ambition is to achieve a recurrent annual saving of £200 million to £300 million by 2021, through the increased use of the best value biological medicines in a proactive, systematic, and safe way.8

Side-effects

  • The safety profile of Hulio is similar to its RP; the most commonly reported adverse reactions are:2
    • infections (such as nasopharyngitis, upper respiratory tract infection, and sinusitis); injection site reactions (erythema, itching, haemorrhage, pain, or swelling); headache; and musculoskeletal pain
  • Serious adverse reactions have been reported for adalimumab:2
    • tumour necrosis factor antagonists, such as adalimumab, affect the immune system and their use may affect the body’s defence against infection and cancer
  • See the Summary of Product Characteristics for full details of undesirable effects.2

References

  1. EU Commission. What you need to know about biosimilar medicinal products. Available at: www.medicinesforeurope.com/wp-content/uploads/2016/03/biosimilars_report_en.pdf
  2. European Medicines Agency. Hulio product information. Available at: www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/004429/WC500255749.pdf
  3. British National Formulary. Adalimumab. Available at: beta-bnf.nice.org.uk/drug/adalimumab.html (accessed 2 September 2018).
  4. National Rheumatoid Arthritis Society (NRAS). NRAS position paper on biosimilar medicines. Revised December, 2017. Available at: www.nras.org.uk/data/files/About%20RA/How%20is%20RA%20managed/NRAS%20Revised%20position%20paper%20biosimilars%20December%202017%20PCT.pdf
  5. NICE. Biosimilar medicines. Key therapeutic topic (KTT15). NICE, 2016 (last updated 2018). Available at: nice.org.uk/guidance/ktt15
  6. Alten R, Glover J, Matsunaga N et al. OP0021 Efficacy and safety results of a phase iii study comparing fkb327, an adalimumab biosimilar, with the adalimumab reference product in patients with active rheumatoid arthritis. Ann Rheum Dis 2017; 76 (suppl. 2): 59. DOI: 10.1136/annrheumdis-2017-eular.2220
  7. Genovese M, Glover J, Matsunaga N et al. Efficacy, safety and immunogenicity in randomized, double-blind (DB) and open-label extension (OLE) studies comparing FKB327, an adalimumab biosimilar, with the adalimumab reference product (Humira®; RP) in patients (pts) with active rheumatoid arthritis (RA) Arthritis Rheumatol 2017; 69 (suppl 10).
  8. NHS Commissioning Support. Toolkit for implementing best value adalimumab, updated August 2018. NHS Specialist Pharmacist Service. Available at: www.sps.nhs.uk/articles/adalimumab-toolkit-for-commissioners-and-providers/ (accessed 2 September 2018).

ADA-2018-0014

Date of preparation: October 2018