For US healthcare professionals only
Q-code: Q5156

AVTOZMA was compared with Actemra® in a randomized trial of adult patients with moderately to severely active rheumatoid arthritis (RA)1

AVTOZMA and Actemra patients continued therapy for up to 52 weeks1

Inclusion criteria: Patients ≥18 years with moderately to severely active RA, inadequately responsive to ≥1 disease-modifying anti-rheumatic drug (DMARD)1

  • Primary endpoint: Equivalent DAS28-ESR change from baseline at weeks 12 and 241
  • Additional endpoints: ACR20/50/70, CDAI, SDAI, ACR/EULAR remission, CRP, PK, DAS28-ESR at 52 weeks, immunogenicity, and safety1
  • Treatment period 1 (week 0 to week 24): Patients were randomized to receive AVTOZMA or Actemra 8 mg/kg IV every 4 weeks1
  • Treatment period 2 (week 24 to week 52): Patients receiving Actemra were re-randomized 1:1 to continue Actemra or switch to AVTOZMA; patients initially receiving AVTOZMA continued receiving AVTOZMA1

ACR20/50/70, American College of Rheumatology 20%, 50%, and 70% improvement criteria; CDAI, Clinical Disease Activity Index; CRP, C-reactive protein; DAS28-ESR, Disease Activity Score in 28 joints using ESR, erythrocyte sedimentation rate; DMARD, disease-modifying anti-rheumatic drug; EULAR, European Alliance of Associations for Rheumatology; IV, intravenous; PK, pharmacokinetics; SDAI, Simplified Disease Activity Index.

AVTOZMA and Actemra showed similar improvement in RA1

AVTOZMA and Actemra showed similar results at weeks 12 and 241

Mean DAS28-ESR score improvement from
baseline at weeks 12 and 241

  • Mean change from baseline in DAS28-ESR at weeks 12 and 24 was assessed as the primary endpoint1*
  • For the demonstration of efficacy, the 95% and 90% CIs for the treatment differences at week 12 and week 24, respectively, were entirely contained within the predefined equivalence margins of -0.6 to 0.6 and -0.6 to 0.5. This demonstrated therapeutic equivalence between AVTOZMA and Actemra groups in the mean change from baseline DAS28-ESR at
    • Week 12 analysis (ANCOVA, ITT): treatment difference = −0.01 (95% CI −0.26, 0.24)1
    • Week 24 analysis (ANCOVA with multiple imputation, ITT): treatment difference = −0.10 (90% CI −0.30, 0.10)1
  • Based partly on the findings of this study, AVTOZMA has been approved as biosimilar to Actemra across all Actemra indications, including rheumatoid arthritis, giant cell arteritis, polyarticular juvenile idiopathic arthritis, systemic juvenile idiopathic arthritis, cytokine release syndrome, and COVID-19 in hospitalized adult patients requiring supplemental oxygen or ventilation support1,2
  • The FDA looks at a wide variety of tests and data to determine that a drug is biosimilar to another, including clinical trials, blood and immune system evaluations, and chemical analyses. AVTOZMA passed those tests and is officially biosimilar to Actemra1,3

ANCOVA, analysis of covariance; CI, confidence interval; DAS28-ESR, Disease Activity Score in 28 joints using ESR, erythrocyte sedimentation rate; ITT, intent-to-treat.

*The DAS28 is a measurement to assess disease activity in patients with rheumatoid arthritis that includes the following 4 items: number of painful joints out of 28 assessed joints; number of swollen joints out of 28 assessed joints; the erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) concentration; and a visual analogue scale (VAS) that measures the patient’s general health.4

AVTOZMA and Actemra patients showed similar DAS28-ESR to 52 weeks5

AVTOZMA and Actemra group mean DAS28-ESR scores were consistent—including in the switch population5

Mean DAS28-ESR score change from baseline
at week 525

  • Mean change from baseline in DAS28-ESR at week 52 was assessed as a pre-planned follow-up analysis5

DAS28-ESR, Disease Activity Score in 28 joints using ESR, erythrocyte sedimentation rate.

AVTOZMA delivered similar drug exposure to Actemra1,5,6

Serum concentrations (µg/mL) during treatment periods 1 and 21,5,6

  • PK data were assessed as a secondary endpoint1
  • Patients receiving the 8 mg/kg dose of AVTOZMA demonstrated serum concentrations comparable to those taking the same dose of Actemra at all measured time points1,5,6

PK, pharmacokinetics.

AVTOZMA immune profile was consistent with Actemra profile1

AVTOZMA and Actemra ADA profiles were similar at week 32, even in the switch population1

Patients ADA+ at week 321

  • Immunogenicity was assessed as a secondary endpoint1
  • Similar trends were observed across treatment groups in treatment period 21
  • No change in ADA frequency after switching from Actemra to AVTOZMA1

ADA, antidrug antibody; ADA+, antidrug antibody positive.

AVTOZMA safety profile is similar to Actemra1

TEAEs: Patients with at least one adverse event related to study drug1

  • Safety was assessed as a secondary endpoint1
  • The most common adverse reactions reported in patients treated with AVTOZMA were1:
    • AVTOZMA (TP1): Upper respiratory tract infection (21.4%), increased alanine aminotransferase (15.8%), leukopenia (8.5%), neutropenia (8.1%), nasopharyngitis (7.7%), hypercholesterolemia (6.8%), increased aspartate aminotransferase (5.1%)
    • Continued AVTOZMA (TP2): Increased alanine aminotransferase (7.6%), leukopenia (4.9%), upper respiratory tract infection (4.4%), increased aspartate aminotransferase (4.4%)
    • Switched to AVTOZMA (TP2): Leukopenia (6.4%), increased alanine aminotransferase (4.5%), increased aspartate aminotransferase (4.5%), upper respiratory tract infection (3.6%)

TESAEs: Patients with at least one serious adverse event related to study drug1

  • Serious adverse events reported were1:
    • AVTOZMA (TP1): 10 patients (4.3%) experienced ≥1 serious adverse event, including: infections (3 patients, 1.3%); hypersensitivity (3 patients; 1.3%); hemorrhage (3 patients, 1.3%)
    • Continued AVTOZMA (TP2): 4 patients (1.8%) experienced serious adverse events, including: infection (peritonitis) in 1 patient (0.4%) — a fatal TESAE, also classified as gastrointestinal perforation but deemed unrelated to study drug; hemorrhage in 1 patient (0.4%)
    • Switched to AVTOZMA (TP2): 2 patients (1.8%) experienced serious adverse events, including hemorrhage (2 patients, 1.8%), one of which was a grade 3 uterine hemorrhage

TEAE, treatment-emergent adverse event; TESAE, treatment-emergent serious adverse event; TP1, treatment period 1; TP2, treatment period 2.

AVTOZMA and Actemra demonstrated similar safety profiles1

TEAEs in ≥3% of patients in any treatment group1

Started
Continued
Switched To
  • Safety was assessed as a secondary endpoint1
  • During treatment period 1, similar proportions of patients in the AVTOZMA group (80.3%) and the Actemra group (78.9%) experienced TEAEs of any intensity1
  • During treatment period 2, the incidence of TEAEs was also similar among patients continuing AVTOZMA (49.8%), continuing Actemra (45.0%), and those switching to AVTOZMA (42.7%)1

TEAE, treatment-emergent adverse event; TP1, treatment period 1; TP2, treatment period 2.

AVTOZMA demonstrated a similar safety profile to Actemra—shown to 52 weeks5

Overview of TEAEs up to week 525

Treatment Period 2
(Week 24 - Week 52)
Overall Period
(Week 0 - Week 52)
  • Safety at week 52 was assessed as a pre-planned follow-up analysis5

GI, gastrointestinal; TEAE, treatment-emergent adverse event; TEAESI, treatment-emergent adverse event of special interest; TESAE, treatment-emergent serious adverse event.

*Peritonitis (unrelated) occurred after gastroscopy and was classified as TESAE, TEAESI of infection, TEAESI of GI, and TEAE leading to death.

†One grade 3 uterine hemorrhage reported in switched-to-AVTOZMA group; not considered medically significant.

References: 1. Smolen JS, Trefler J, Racewicz A, et al. Efficacy and safety of CT-P47 versus reference tocilizumab: 32-week results of a randomised, active-controlled, double-blind, phase III study in patients with rheumatoid arthritis, including 8 weeks of switching data from reference tocilizumab to CT-P47. RMD Open. 2024;10:e004514. doi:10.1136/rmdopen-2024-004514 2. AVTOZMA Prescribing Information. Celltrion USA, Inc; 2025. 3. US Food and Drug Administration. Biosimilar Product Regulatory Review and Approval. Accessed March 17, 2025. https://www.fda.gov/files/drugs/published/Biosimilar-Product-Regulatory-Review-and-Approval.pdf 4. Inoue E, Yamanaka H, Hara M, Tomatsu T, Kamatani N. Comparison of Disease Activity Score (DAS)28-erythrocyte sedimentation rate and DAS28-C-reactive protein threshold values. Ann Rheum Dis. 2007;66:407-409. 5. Burmester G, Trefler J, Racewicz A, et al. Similar efficacy, PK, safety, and immunogenicity of tocilizumab biosimilar (CT-P47) and reference tocilizumab in patients with moderate-to-severe active rheumatoid arthritis: week 52 results from the phase III single transition study [abstract]. Arthritis Rheumatol. 2024;76(suppl 9). Accessed July 9, 2025. https://acrabstracts.org/abstract/similar-efficacy-pk-safety-and-immunogenicity-of-tocilizumab-biosimilar-ct-p47-and-reference-tocilizumab-in-patients-with-moderate-to-severe-active-rheumatoid-arthritis-week-52-results-from-the/ 6. Smolen JS, Trefler J, Racewicz A, et al. Supplementary material to: Efficacy and safety of CT-P47 versus reference tocilizumab: 32-week results of a randomised, active-controlled, double-blind, phase III study in patients with rheumatoid arthritis, including 8 weeks of switching data from reference tocilizumab to CT-P47. RMD Open. 2024;10:e004514. doi:10.1136/rmdopen-2024-004514

IMPORTANT SAFETY INFORMATION

WARNING: RISK OF SERIOUS INFECTIONS

Patients treated with tocilizumab products including AVTOZMA are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids.

If a serious infection develops, interrupt AVTOZMA until the infection is controlled. Reported infections include:

  • Active tuberculosis, which may present with pulmonary or extrapulmonary disease. Patients, except those with COVID-19, should be tested for latent tuberculosis before AVTOZMA use and during therapy. Treatment for latent infection should be initiated prior to AVTOZMA use.
  • Invasive fungal infections, including candidiasis, aspergillosis, and pneumocystis. Patients with invasive fungal infections may present with disseminated, rather than localized, disease.
  • Bacterial, viral and other infections due to opportunistic pathogens.

The risks and benefits of treatment with AVTOZMA should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection.

Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with AVTOZMA, including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy.

Contraindications: Known hypersensitivity to tocilizumab products.

Serious Infections. Serious and sometimes fatal infections, including bacterial, mycobacterial, invasive fungal, viral, and opportunistic infections, have been reported with tocilizumab products, including AVTOZMA. Common serious infections include pneumonia, urinary tract infections, cellulitis, herpes zoster, and sepsis, while opportunistic infections such as tuberculosis and cryptococcus have also occurred. Patients with chronic or recurrent infections, tuberculosis exposure, or underlying conditions predisposing to infections should have the risks and benefits of AVTOZMA carefully evaluated. Monitor patients closely during and after treatment for signs of infection, and discontinue AVTOZMA if a serious infection develops, initiating appropriate antimicrobial therapy as needed.

Gastrointestinal (GI) Perforation. Gastrointestinal perforation events, primarily associated with diverticulitis, have been reported in clinical trials of tocilizumab. Use AVTOZMA cautiously in patients at increased risk for gastrointestinal perforation. Promptly evaluate any patient experiencing new abdominal symptoms to ensure early detection and management of this condition.

Hepatotoxicity. Serious hepatic injury, including cases of liver transplant and death, has occurred with tocilizumab products, with onset ranging from months to years. Some cases involved marked transaminase elevations (>5x ULN), while others presented with mild elevations and symptoms of liver dysfunction. Risk is higher with hepatotoxic drugs like methotrexate. Baseline and regular liver tests are required for RA, GCA, PJIA, and SJIA patients, with specific monitoring intervals based on the condition. Do not initiate AVTOZMA if ALT or AST >1.5x ULN (RA/GCA) or >10x ULN (COVID-19), and discontinue if ALT or AST >5x ULN. Evaluate symptoms of liver injury promptly, and only restart treatment if liver test abnormalities are resolved and attributed to another cause.

Changes in Laboratory Parameters. Treatment with tocilizumab products, including AVTOZMA, has been associated with neutropenia, thrombocytopenia, elevated liver enzymes, and lipid abnormalities. Infections are uncommon with treatment-related neutropenia, but AVTOZMA should not be initiated in RA or GCA patients with ANC <2000/mm³ or platelet counts <100,000/mm³, and treatment is not recommended if ANC drops below 500/mm³ or platelets below 50,000/mm³. For COVID-19 patients, AVTOZMA is not recommended with ANC <1000/mm³ or platelets <50,000/mm³. Monitor neutrophils, platelets, and liver enzymes 4-8 weeks after starting therapy and every 3 months thereafter, adjusting treatment as needed. Lipid levels, including cholesterol and triglycerides, may increase and should be assessed 4-8 weeks after initiation, with management per clinical guidelines. A similar pattern is observed in PJIA and SJIA, requiring specific monitoring intervals for these populations. Refer to Dosage and Administration for modifications based on test results.

Immunosuppression. The effect of tocilizumab products on malignancy development is unknown, though malignancies were observed in clinical studies. As an immunosuppressant, AVTOZMA may increase the risk of malignancies.

Hypersensitivity Reactions, Including Anaphylaxis. Hypersensitivity reactions, including anaphylaxis and fatal events, have been reported with tocilizumab products. Anaphylaxis requiring discontinuation occurred in 0.1% to 0.7% of trial patients, with postmarketing cases reported at various doses, with or without premedication, and as early as the first infusion. AVTOZMA intravenous infusions must be administered by healthcare professionals equipped to manage anaphylaxis. For subcutaneous use, patients must seek immediate medical attention if hypersensitivity symptoms occur. Discontinue AVTOZMA permanently if anaphylaxis or other hypersensitivity reaction occurs. Do not use in patients with known hypersensitivity to tocilizumab products.

Demyelinating Disorders. The impact of tocilizumab on demyelinating disorders is unknown, but rare cases like multiple sclerosis and polyneuropathy were reported in RA studies. Monitor for symptoms and use caution in patients with preexisting or recent demyelinating disorders.

Active Hepatic Disease and Hepatic Impairment. Treatment with AVTOZMA is not recommended.

Live Vaccines. Avoid concurrent use of live vaccines with AVTOZMA, as clinical safety and secondary transmission risk are unknown. Follow guidelines on timing between live vaccines and AVTOZMA.

Adverse Reactions reported in ≥5% of tocilizumab-treated patients include upper respiratory tract infections, nasopharyngitis, headache, hypertension, increased ALT, and injection site reactions.

Please see full Prescribing Information, including BOXED WARNING.

INDICATIONS

AVTOZMA® (tocilizumab-anoh) is an interleukin-6 (IL-6) receptor antagonist indicated for treatment of:

  • Rheumatoid Arthritis (RA): Adult patients with moderately to severely active RA who have had an inadequate response to one or more Disease-Modifying Anti-Rheumatic Drugs (DMARDs).
  • Giant Cell Arteritis (GCA): Adult patients with GCA.
  • Polyarticular Juvenile Idiopathic Arthritis (PJIA): Patients 2+ years old with active PJIA.
  • Systemic Juvenile Idiopathic Arthritis (SJIA): Patients 2+ years old with active SJIA.
  • Cytokine Release Syndrome (CRS): Adults and pediatric patients 2 years of age and older with chimeric antigen receptor (CAR) T-cell-induced severe or life-threatening cytokine release syndrome
  • Coronavirus Disease 2019 (COVID-19): Hospitalized adult patients with COVID-19 who are receiving systemic corticosteroids and require supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).

INDICATIONS

AVTOZMA® (tocilizumab-anoh) is an interleukin-6 (IL-6) receptor antagonist indicated for treatment of:

  • Rheumatoid Arthritis (RA): Adult patients with moderately to severely active RA who have had an inadequate response to one or more Disease-Modifying Anti-Rheumatic Drugs (DMARDs).
  • Giant Cell Arteritis (GCA): Adult patients with GCA.
  • Polyarticular Juvenile Idiopathic Arthritis (PJIA): Patients 2+ years old with active PJIA.
  • Systemic Juvenile Idiopathic Arthritis (SJIA): Patients 2+ years old with active SJIA.
  • Cytokine Release Syndrome (CRS): Adults and pediatric patients 2 years of age and older with chimeric antigen receptor (CAR) T-cell-induced severe or life-threatening cytokine release syndrome
  • Coronavirus Disease 2019 (COVID-19): Hospitalized adult patients with COVID-19 who are receiving systemic corticosteroids and require supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).

IMPORTANT SAFETY INFORMATION

WARNING: RISK OF SERIOUS INFECTIONS

Patients treated with tocilizumab products including AVTOZMA are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids.

If a serious infection develops, interrupt AVTOZMA until the infection is controlled. Reported infections include:

  • Active tuberculosis, which may present with pulmonary or extrapulmonary disease. Patients, except those with COVID-19, should be tested for latent tuberculosis before AVTOZMA use and during therapy. Treatment for latent infection should be initiated prior to AVTOZMA use.
  • Invasive fungal infections, including candidiasis, aspergillosis, and pneumocystis. Patients with invasive fungal infections may present with disseminated, rather than localized, disease.
  • Bacterial, viral and other infections due to opportunistic pathogens.

The risks and benefits of treatment with AVTOZMA should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection.

Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with AVTOZMA, including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy.

Contraindications: Known hypersensitivity to tocilizumab products.

Serious Infections. Serious and sometimes fatal infections, including bacterial, mycobacterial, invasive fungal, viral, and opportunistic infections, have been reported with tocilizumab products, including AVTOZMA. Common serious infections include pneumonia, urinary tract infections, cellulitis, herpes zoster, and sepsis, while opportunistic infections such as tuberculosis and cryptococcus have also occurred. Patients with chronic or recurrent infections, tuberculosis exposure, or underlying conditions predisposing to infections should have the risks and benefits of AVTOZMA carefully evaluated. Monitor patients closely during and after treatment for signs of infection, and discontinue AVTOZMA if a serious infection develops, initiating appropriate antimicrobial therapy as needed.

Gastrointestinal (GI) Perforation. Gastrointestinal perforation events, primarily associated with diverticulitis, have been reported in clinical trials of tocilizumab. Use AVTOZMA cautiously in patients at increased risk for gastrointestinal perforation. Promptly evaluate any patient experiencing new abdominal symptoms to ensure early detection and management of this condition.

Hepatotoxicity. Serious hepatic injury, including cases of liver transplant and death, has occurred with tocilizumab products, with onset ranging from months to years. Some cases involved marked transaminase elevations (>5x ULN), while others presented with mild elevations and symptoms of liver dysfunction. Risk is higher with hepatotoxic drugs like methotrexate. Baseline and regular liver tests are required for RA, GCA, PJIA, and SJIA patients, with specific monitoring intervals based on the condition. Do not initiate AVTOZMA if ALT or AST >1.5x ULN (RA/GCA) or >10x ULN (COVID-19), and discontinue if ALT or AST >5x ULN. Evaluate symptoms of liver injury promptly, and only restart treatment if liver test abnormalities are resolved and attributed to another cause.

Changes in Laboratory Parameters. Treatment with tocilizumab products, including AVTOZMA, has been associated with neutropenia, thrombocytopenia, elevated liver enzymes, and lipid abnormalities. Infections are uncommon with treatment-related neutropenia, but AVTOZMA should not be initiated in RA or GCA patients with ANC <2000/mm³ or platelet counts <100,000/mm³, and treatment is not recommended if ANC drops below 500/mm³ or platelets below 50,000/mm³. For COVID-19 patients, AVTOZMA is not recommended with ANC <1000/mm³ or platelets <50,000/mm³. Monitor neutrophils, platelets, and liver enzymes 4-8 weeks after starting therapy and every 3 months thereafter, adjusting treatment as needed. Lipid levels, including cholesterol and triglycerides, may increase and should be assessed 4-8 weeks after initiation, with management per clinical guidelines. A similar pattern is observed in PJIA and SJIA, requiring specific monitoring intervals for these populations. Refer to Dosage and Administration for modifications based on test results.

Immunosuppression. The effect of tocilizumab products on malignancy development is unknown, though malignancies were observed in clinical studies. As an immunosuppressant, AVTOZMA may increase the risk of malignancies.

Hypersensitivity Reactions, Including Anaphylaxis. Hypersensitivity reactions, including anaphylaxis and fatal events, have been reported with tocilizumab products. Anaphylaxis requiring discontinuation occurred in 0.1% to 0.7% of trial patients, with postmarketing cases reported at various doses, with or without premedication, and as early as the first infusion. AVTOZMA intravenous infusions must be administered by healthcare professionals equipped to manage anaphylaxis. For subcutaneous use, patients must seek immediate medical attention if hypersensitivity symptoms occur. Discontinue AVTOZMA permanently if anaphylaxis or other hypersensitivity reaction occurs. Do not use in patients with known hypersensitivity to tocilizumab products.

Demyelinating Disorders. The impact of tocilizumab on demyelinating disorders is unknown, but rare cases like multiple sclerosis and polyneuropathy were reported in RA studies. Monitor for symptoms and use caution in patients with preexisting or recent demyelinating disorders.

Active Hepatic Disease and Hepatic Impairment. Treatment with AVTOZMA is not recommended.

Live Vaccines. Avoid concurrent use of live vaccines with AVTOZMA, as clinical safety and secondary transmission risk are unknown. Follow guidelines on timing between live vaccines and AVTOZMA.

Adverse Reactions reported in ≥5% of tocilizumab-treated patients include upper respiratory tract infections, nasopharyngitis, headache, hypertension, increased ALT, and injection site reactions.

Please see full Prescribing Information, including BOXED WARNING.

INDICATIONS

AVTOZMA® (tocilizumab-anoh) is an interleukin-6 (IL-6) receptor antagonist indicated for treatment of:

  • Rheumatoid Arthritis (RA): Adult patients with moderately to severely active RA who have had an inadequate response to one or more Disease-Modifying Anti-Rheumatic Drugs (DMARDs).
  • Giant Cell Arteritis (GCA): Adult patients with GCA.
  • Polyarticular Juvenile Idiopathic Arthritis (PJIA): Patients 2+ years old with active PJIA.
  • Systemic Juvenile Idiopathic Arthritis (SJIA): Patients 2+ years old with active SJIA.
  • Cytokine Release Syndrome (CRS): Adults and pediatric patients 2 years of age and older with chimeric antigen receptor (CAR) T-cell-induced severe or life-threatening cytokine release syndrome
  • Coronavirus Disease 2019 (COVID-19): Hospitalized adult patients with COVID-19 who are receiving systemic corticosteroids and require supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).