REMSIMA

What it is

REMSIMA is an approved biosimilar to the reference product REMICADE (infliximab). Comparability in safety, efficacy and quality between REMSIMA and REMICADE has been established. REMSIMA is available as 100 mg powder for injection vial, 120 mg solution for injection in pre-filled syringe, and 120 mg solution for injection in pre-filled pen.

Approved indications

**Intravenous formulation (100 mg powder for injection):** — Rheumatoid arthritis in adults: reduction of signs and symptoms and prevention of structural joint damage in patients with active disease despite methotrexate treatment or in patients with active disease who have not previously received methotrexate, administered in combination with methotrexate. — Ankylosing spondylitis: reduction of signs and symptoms and improvement in physical function in patients with active disease. — Psoriatic arthritis: treatment of signs and symptoms and improvement in physical function in adult patients with active and progressive disease who have responded inadequately to disease-modifying anti-rheumatic drug therapy. — Psoriasis: treatment of adult patients with moderate to severe plaque psoriasis for whom phototherapy or conventional systemic treatments have been inadequate or are inappropriate. — Crohn's disease in adults and children and adolescents aged 6 to 17 years: treatment of moderate to severe disease to reduce signs and symptoms and to induce and maintain clinical remission in patients with inadequate response to conventional therapies. — Refractory fistulising Crohn's disease: reducing the number of draining enterocutaneous and rectovaginal fistulas and maintaining fistula closure in adult patients. — Ulcerative colitis in adults and children and adolescents aged 6 to 17 years: treatment of moderately severe to severe active disease in patients with inadequate response to conventional therapy. **Subcutaneous formulation (120 mg solution for injection):** — Rheumatoid arthritis in adults: reduction of signs and symptoms and prevention of structural joint damage in patients with active disease despite methotrexate treatment or in patients with active disease who have not previously received methotrexate, administered in combination with methotrexate. — Ankylosing spondylitis: reduction of signs and symptoms and improvement in physical function in patients with active disease. — Psoriatic arthritis: treatment of signs and symptoms and improvement in physical function in adult patients with active and progressive disease who have responded inadequately to disease-modifying anti-rheumatic drug therapy. — Psoriasis: treatment of adult patients with moderate to severe plaque psoriasis for whom phototherapy or conventional systemic treatments have been inadequate or are inappropriate. — Crohn's disease in adults: treatment of moderate to severe disease to reduce signs and symptoms and to induce and maintain clinical remission in patients with inadequate response to conventional therapies. — Refractory fistulising Crohn's disease: reducing the number of draining enterocutaneous and rectovaginal fistulas and maintaining fistula closure in adult patients. — Ulcerative colitis in adults: treatment of moderately severe to severe active disease in patients with inadequate response to conventional therapy.

Dosing overview

**Intravenous formulation:** For rheumatoid arthritis, the initial dose is 3 mg/kg intravenous infusion followed by additional 3 mg/kg doses at 2 and 6 weeks, then every 8 weeks thereafter. For ankylosing spondylitis, the dose is 5 mg/kg given as intravenous infusion at weeks 0, 2 and 6, then every 6 weeks thereafter. For psoriatic arthritis, the dose is 5 mg/kg at weeks 0, 2 and 6, then every 8 weeks thereafter. For psoriasis, the dose is 5 mg/kg at weeks 0, 2 and 6, then every 8 weeks thereafter. For Crohn's disease in adults and children aged 6 to 17 years, the induction regimen is 5 mg/kg at weeks 0, 2 and 6, followed by maintenance of 5 mg/kg every 8 weeks. For refractory fistulising Crohn's disease, the induction regimen is 5 mg/kg at weeks 0, 2 and 6, followed by maintenance of 5 mg/kg every 8 weeks. For ulcerative colitis in adults and children aged 6 to 17 years, the dose is 5 mg/kg at weeks 0, 2 and 6, then every 8 weeks thereafter. **Subcutaneous formulation:** For rheumatoid arthritis, the recommended maintenance dose is 120 mg once every 2 weeks. For Crohn's disease, the recommended dose is 120 mg once every 2 weeks. For fistulising Crohn's disease, ulcerative colitis, ankylosing spondylitis, psoriatic arthritis and psoriasis, the recommended dose is 120 mg once every 2 weeks.

Key safety warnings

REMSIMA is contraindicated in patients with severe infections such as sepsis, abscesses, tuberculosis and opportunistic infections. Bacterial infections including sepsis and pneumonia, mycobacterial infections including tuberculosis, invasive fungal infections, and opportunistic infections have been observed in patients receiving infliximab, some of which have been fatal, with opportunistic infections including pneumocystosis, candidiasis, listeriosis and aspergillosis having mortality rates exceeding 5%. Patients must be evaluated for tuberculosis risk and tested for latent tuberculosis prior to initiation, including tuberculin skin testing and chest x-ray. Infliximab has been associated with acute infusion effects, systemic injection reactions, anaphylactic shock and delayed hypersensitivity reactions, including urticaria, dyspnoea, bronchospasm, laryngeal oedema, pharyngeal oedema and hypotension occurring during or within 2 hours of infusion. Antibodies to infliximab may develop in some patients and have been associated with an increased frequency of infusion reactions and may be associated with an increased risk of serious infusion reactions. Treatment with infliximab may result in the formation of autoantibodies and development of a lupus-like syndrome, as the relative deficiency of TNF-alpha caused by anti-TNF therapy may result in the initiation of an autoimmune process in genetically susceptible patients. Infliximab has been associated with seizure and new onset or exacerbation of clinical symptoms and/or radiographic evidence of central nervous system demyelinating disorders including multiple sclerosis and optic neuritis, and peripheral demyelinating disorders including Guillain-Barré syndrome. In controlled portions of clinical trials of TNF-blocking agents, more cases of lymphoma have been observed among patients receiving a TNF blocker compared with control patients, and during clinical trials of infliximab the incidence of lymphoma in infliximab-treated patients was higher than expected in the general population, though the occurrence was rare. Post-marketing cases of hepatosplenic T-cell lymphoma have been reported in patients treated with infliximab, a rare type with very aggressive disease course that is usually fatal, with almost all patients having received treatment with azathioprine or 6-mercaptopurine concomitantly with or immediately prior to a TNF-blocker. Reactivation of hepatitis B has occurred in patients receiving infliximab who are chronic carriers of the virus, and patients should be tested for hepatitis B infection before initiating treatment.

Contraindications

REMSIMA is contraindicated in patients with severe infections such as sepsis, abscesses, tuberculosis and opportunistic infections. REMSIMA should not be given to patients with a history of hypersensitivity to infliximab, to other murine proteins or to any excipient of the product. Concurrent administration of REMSIMA and anakinra is contraindicated. Do not initiate therapy in patients with congestive heart failure.

PBS listing

REMSIMA 120 mg solution for injection in pre-filled pen is listed on the PBS with 21 items at an ex-manufacturer price of A$252.40, with streamlined and authority-required restrictions. REMSIMA 120 mg solution for injection in pre-filled syringe is listed on the PBS with 21 items at an ex-manufacturer price of A$332.80, with authority-required and streamlined restrictions.

Regulatory history

REMSIMA infliximab 100 mg powder for injection vial was first listed on the ARTG on 27 November 2015. REMSIMA infliximab 120 mg solution for injection pre-filled syringe and pre-filled syringe in auto-injector pen formulations were first listed on the ARTG on 12 November 2020. In November 2017, PBAC recommended a change to multiple indications with all initial treatment restrictions remaining authority required in writing and continuing restrictions split into first continuing and subsequent continuing authority required streamlined. In March 2022, PBAC recommended REMSIMA for ankylosing spondylitis, psoriatic arthritis, chronic plaque psoriasis and refractory fistulising Crohn's disease as subcutaneous injections.