Explore Tocilizumab (Actemra) and Upadacitinib (Rinvoq) – two advanced medications for autoimmune diseases in the USA. Understand their differences and how they work.

The landscape of treatment for chronic autoimmune and inflammatory conditions in the USA has been significantly transformed by the development of targeted therapies. Among these, Tocilizumab (marketed as Actemra) and Upadacitinib (marketed as Rinvoq) represent distinct yet powerful approaches to managing debilitating diseases such as rheumatoid arthritis (RA), psoriatic arthritis (PsA), and others.

While both aim to quell inflammation and improve patient outcomes, their mechanisms of action, administration routes, and specific indications differ, influencing their selection in clinical practice across the United States.

Tocilizumab (Actemra): An IL-6 Receptor Antagonist

Tocilizumab, sold under the brand name Actemra by Genentech (a member of the Roche Group), is a biologic medication. It is a humanized monoclonal antibody that targets the interleukin-6 (IL-6) receptor. IL-6 is a pro-inflammatory cytokine, a signaling protein that plays a crucial role in driving inflammation in various autoimmune diseases. By blocking the IL-6 receptor, tocilizumab prevents IL-6 from binding and initiating inflammatory processes, thereby reducing inflammation and symptoms.

In the USA, Actemra is FDA-approved for a range of conditions:

• Rheumatoid Arthritis (RA): For adult patients with moderately to severely active RA who have had an inadequate response to one or more disease-modifying anti-rheumatic drugs (DMARDs), including methotrexate. It can be used as monotherapy or in combination with other non-biologic DMARDs.  
• Giant Cell Arteritis (GCA): For adult patients with this systemic vasculitis.
• Systemic Sclerosis-Associated Interstitial Lung Disease (SSc-ILD): For slowing the rate of decline in pulmonary function in adults with this progressive lung disease.  
• Polyarticular Juvenile Idiopathic Arthritis (PJIA) and Systemic Juvenile Idiopathic Arthritis (SJIA): For active forms of these pediatric autoimmune conditions in patients 2 years of age and older.
• Cytokine Release Syndrome (CRS): For severe or life-threatening CAR T cell-induced CRS in adults and pediatric patients 2 years of age and older.
• COVID-19: For hospitalized adult patients receiving systemic corticosteroids and requiring supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).  

Actemra can be administered either as an intravenous (IV) infusion, typically given every 4 weeks, or as a subcutaneous (SC) injection (prefilled syringe or autoinjector) administered weekly or every other week, depending on the condition and patient weight. This flexibility in administration can be beneficial for patients.

Upadacitinib (Rinvoq): A Selective JAK Inhibitor

Upadacitinib, marketed as Rinvoq by AbbVie, is a targeted synthetic DMARD (tsDMARD) and falls into the class of Janus kinase (JAK) inhibitors. Unlike biologics which are large protein molecules often administered by injection, JAK inhibitors are small molecules taken orally. Rinvoq specifically inhibits JAK1, a signaling pathway involved in the inflammatory cascade. By selectively blocking JAK1, Rinvoq interferes with the signaling of several cytokines and growth factors involved in various autoimmune diseases.

In the USA, Rinvoq is FDA-approved for:

• Rheumatoid Arthritis (RA): For adults with moderately to severely active RA who have had an inadequate response or intolerance to one or more TNF blockers.  
• Psoriatic Arthritis (PsA): For adults with active PsA who have had an inadequate response or intolerance to one or more TNF blockers.
• Ankylosing Spondylitis (AS): For adults with active AS who have had an inadequate response to one or more TNF blockers.
• Non-radiographic Axial Spondyloarthritis (nr-axSpA): For adults with active nr-axSpA with objective signs of inflammation who have had an inadequate response or intolerance to a TNF blocker.
• Atopic Dermatitis (AD): For adults and pediatric patients 12 years of age and older with refractory, moderate to severe AD whose disease is not adequately controlled with other systemic drug products, including biologics, or when use of those therapies is inadvisable.  
• Ulcerative Colitis (UC): For adults with moderately to severely active UC who have had an inadequate response or intolerance to one or more TNF blockers.  
• Crohn's Disease (CD): For adults with moderately to severely active CD who have had an inadequate response or intolerance to one or more TNF blockers.

Rinvoq is taken orally once daily as an extended-release tablet. This oral administration can be a significant advantage for patients who prefer pills over injections.

Comparing Tocilizumab (Actemra) and Upadacitinib (Rinvoq) in the USA

When comparing these two advanced therapies, several factors are considered by healthcare providers in the USA:

• Mechanism of Action: Actemra targets a specific cytokine receptor (IL-6R), while Rinvoq broadly inhibits a signaling pathway (JAK1). This fundamental difference can lead to varying efficacy and side effect profiles.
• Indications: While both treat RA, Rinvoq has a broader range of approved indications for spondyloarthritis, atopic dermatitis, and inflammatory bowel diseases. Actemra has unique approvals for GCA, SSc-ILD, CRS, and certain COVID-19 cases.
• Administration: Actemra requires injections (IV or SC), while Rinvoq is an oral tablet. Patient preference and adherence to treatment are important considerations here.
• Efficacy: Both medications have demonstrated significant efficacy in their approved indications, leading to reductions in disease activity, improvement in physical function, and inhibition of structural damage. In studies for RA, both have shown superiority over conventional DMARDs and, in some head-to-head comparisons, have shown similar or superior efficacy to certain TNF inhibitors.
• Safety Profile and Warnings: Both drugs suppress the immune system and carry a Boxed Warning in the USA regarding the risk of serious infections, including tuberculosis, fungal infections, and opportunistic infections.
  • Actemra has warnings for gastrointestinal perforations, liver enzyme elevations, lipid abnormalities, and neutropenia/thrombocytopenia.
  • Rinvoq also carries warnings for malignancies (especially lymphomas and lung cancer), major adverse cardiovascular events (MACE) such as heart attack and stroke, and thrombosis (blood clots, including deep venous thrombosis and pulmonary embolism). These MACE and thrombosis risks, particularly in patients aged 50 and older with at least one cardiovascular risk factor, have led to increased scrutiny of JAK inhibitors by the FDA.
• Cost and Access: Both are high-cost specialty medications. Access in the USA is largely dictated by insurance coverage, prior authorization requirements, and patient assistance programs offered by the manufacturers. These factors can significantly influence which medication a patient can access.

The choice between Tocilizumab (Actemra) and Upadacitinib (Rinvoq) is a complex medical decision made by rheumatologists and other specialists in consultation with their patients in the USA. It involves a thorough evaluation of the patient's specific condition, disease severity, comorbidities, previous treatment responses, individual risk factors, lifestyle preferences, and insurance coverage. Both medications represent valuable therapeutic options that have significantly improved the lives of many individuals living with chronic inflammatory and autoimmune diseases.