RENFLEXIS

What it is

RENFLEXIS is an approved biosimilar to the reference product REMICADE (infliximab). Comparability in safety, efficacy and quality between RENFLEXIS and REMICADE has been established. RENFLEXIS 100 mg powder for injection is supplied in vials, with each vial containing infliximab 100 mg. RENFLEXIS 120 mg solution for injection is also available in pre-filled syringe and pre-filled pen formulations, each containing 120 mg of infliximab.

Approved indications

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

Dosing overview

**Intravenous formulation (adults across all indications):** For rheumatoid arthritis, the initial dose is 3 mg/kg intravenous infusion followed by additional 3 mg/kg doses at 2 and 6 weeks after the first infusion, then every 8 weeks thereafter. For ankylosing spondylitis, the dose is 5 mg/kg given as an intravenous infusion followed by additional 5 mg/kg doses at 2 and 6 weeks, then every 6 weeks thereafter. For psoriatic arthritis, the dose is 5 mg/kg given as an intravenous infusion followed by additional 5 mg/kg doses at 2 and 6 weeks, then every 8 weeks thereafter. For psoriasis, the dose is 5 mg/kg given as an intravenous infusion followed by additional 5 mg/kg doses at 2 and 6 weeks, then every 8 weeks thereafter. For moderate to severe Crohn's disease in adults and children aged 6 to 17 years, the dose is 5 mg/kg given as a single intravenous infusion as an induction regimen at 0, 2 and 6 weeks followed by a maintenance regimen of 5 mg/kg every 8 weeks thereafter. For refractory fistulising Crohn's disease, the dose is 5 mg/kg given as a single intravenous infusion as an induction regimen at 0, 2 and 6 weeks followed by a maintenance regimen of 5 mg/kg every 8 weeks thereafter. For ulcerative colitis in adults and children aged 6 to 17 years, the dose is 5 mg/kg given as an intravenous infusion followed by additional 5 mg/kg doses at 2 and 6 weeks, then every 8 weeks thereafter. All infusions must be administered over a period of not less than 2 hours. All patients are to be observed for at least one to two hours post infusion for side effects. **Subcutaneous formulation (adults):** For rheumatoid arthritis without intravenous loading doses, RENFLEXIS 120 mg should be given as a subcutaneous injection followed by additional subcutaneous injections at 1, 2, 3 and 4 weeks after the first injection, then every 2 weeks thereafter. The recommended maintenance dose is 120 mg once every 2 weeks. For moderately to severely active Crohn's disease, treatment should be initiated as maintenance therapy 4 weeks after the last administration of two intravenous infusions of infliximab 5 mg/kg given 2 weeks apart, with a recommended dose of 120 mg once every 2 weeks. For fistulising active Crohn's disease, RENFLEXIS 120 mg is given as a subcutaneous injection 4 weeks after the last administration of two intravenous infusions of infliximab 5 mg/kg given 2 weeks apart, with a recommended dose of 120 mg once every 2 weeks. For ulcerative colitis, treatment should be initiated as maintenance therapy 4 weeks after the last administration of two intravenous infusions of infliximab 5 mg/kg given 2 weeks apart, with a recommended dose of 120 mg once every 2 weeks. For ankylosing spondylitis, treatment should be initiated as maintenance therapy 4 weeks after the last administration of two intravenous infusions of infliximab 5 mg/kg given 2 weeks apart, with a recommended dose of 120 mg once every 2 weeks. For psoriatic arthritis, treatment should be initiated as maintenance therapy 4 weeks after the last administration of two intravenous infusions of infliximab 5 mg/kg given 2 weeks apart, with a recommended dose of 120 mg once every 2 weeks. For psoriasis, treatment should be initiated as maintenance therapy 4 weeks after the last administration of two intravenous infusions of infliximab 5 mg/kg given 2 weeks apart, with a recommended dose of 120 mg once every 2 weeks.

Key safety warnings

**Infections:** Bacterial infections including sepsis and pneumonia, mycobacterial infections including tuberculosis (frequently disseminated or extrapulmonary), invasive fungal, viral, and other opportunistic infections have been observed in patients receiving infliximab, and some have been fatal; the most frequently reported opportunistic infections with a mortality rate greater than 5% include pneumocystosis, candidiasis, listeriosis and aspergillosis. Infliximab should not be given to patients with a clinically important, active infection. Patients must be evaluated for tuberculosis risk and tested for latent tuberculosis prior to initiation of infliximab, with evaluation including detailed medical history and appropriate screening tests including tuberculin skin test and chest x-ray. Patients must be monitored closely for infections while on and after treatment with infliximab. Treatment with infliximab must be discontinued if a patient develops a serious infection or sepsis. **Infusion reactions and hypersensitivity:** Infliximab has been associated with acute infusion effects, systemic injection reactions, anaphylactic shock and delayed hypersensitivity reactions, which differ in their time of onset. Hypersensitivity reactions including urticaria, dyspnoea, bronchospasm, laryngeal oedema, pharyngeal oedema, and hypotension have occurred during or within 2 hours of infliximab infusion, therefore all patients receiving infliximab should be observed for at least one to two hours post infusion for side effects. 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. **Congestive heart failure:** Do not initiate therapy in patients with congestive heart failure. Treatment should be discontinued in patients whose congestive heart failure is worsening. **Malignancy:**