Xeljanz (tofacitinib) offers an oral, targeted approach to managing various forms of arthritis in the USA, providing significant relief and slowing disease progression for many patients.

Arthritis encompasses a wide range of conditions characterized by joint inflammation, pain, stiffness, and potential long-term damage. Among the most impactful forms are autoimmune types like rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS), which can significantly diminish a person's quality of life.

For individuals in the United States living with moderately to severely active forms of these conditions, finding effective and convenient treatment is paramount. Xeljanz (tofacitinib), marketed by Pfizer, represents a significant advancement as a targeted synthetic disease-modifying anti-rheumatic drug (tsDMARD), offering an oral option for those who have not responded adequately to conventional therapies.  

Understanding Xeljanz: A Janus Kinase (JAK) Inhibitor

Xeljanz belongs to a class of medications known as Janus kinase (JAK) inhibitors. Unlike traditional DMARDs that broadly suppress the immune system, or biologics that are large protein molecules targeting specific external components of the immune system, JAK inhibitors are small molecules taken orally that work inside cells.  

Here's how Xeljanz works:

• Targeting JAK Enzymes: Janus kinases are a family of enzymes (JAK1, JAK2, JAK3, TYK2) that play a crucial role in the signaling pathways of numerous cytokines and growth factors. These signaling pathways are fundamental to immune cell function and inflammation.  
• Blocking Inflammation Signals: In autoimmune arthritic conditions like RA, PsA, and AS, these JAK pathways are often overactive, leading to excessive inflammation in the joints and other tissues. Xeljanz works by inhibiting the activity of specific JAK enzymes (primarily JAK1 and JAK3). By blocking these enzymes, Xeljanz disrupts the intracellular signaling of various inflammatory cytokines, thereby reducing the inflammation, pain, and swelling associated with these diseases. This targeted approach aims to calm the overactive immune response that drives arthritis progression.  

Indications and Administration in the USA

In the USA, Xeljanz (tofacitinib) is FDA-approved for the treatment of:

• Moderately to severely active Rheumatoid Arthritis (RA): For adult patients who have had an inadequate response or intolerance to one or more TNF blockers. It can be used alone or in combination with non-biologic DMARDs like methotrexate.  
• Active Psoriatic Arthritis (PsA): For adult patients who have had an inadequate response or intolerance to one or more TNF blockers. It is often used in combination with non-biologic DMARDs.  
• Active Ankylosing Spondylitis (AS): For adult patients who have had an inadequate response or intolerance to one or more TNF blockers.  
• Moderately to severely active Ulcerative Colitis (UC): For adult patients who have had an inadequate response or intolerance to one or more TNF blockers.  
• Active Polyarticular Course Juvenile Idiopathic Arthritis (pcJIA): For patients 2 years of age and older who have had an inadequate response or intolerance to one or more TNF blockers.  

A significant advantage of Xeljanz over injectable biologics is its oral administration. It is available as:

• Xeljanz (immediate-release tablet): Typically taken as a 5 mg tablet twice daily.
• Xeljanz XR (extended-release tablet): An 11 mg tablet taken once daily.  
• Xeljanz Oral Solution: For pediatric patients.

This oral dosing offers convenience for patients who prefer not to self-inject or require IV infusions.

Efficacy of Xeljanz in Arthritis Treatment

Clinical trials have demonstrated the effectiveness of Xeljanz in reducing the signs and symptoms of RA, PsA, and AS, improving physical function, and inhibiting the progression of structural joint damage. Many patients begin to experience improvement in their symptoms within the first 12 weeks of starting treatment, with continued benefits over time. Its efficacy has been shown both as monotherapy (in RA, when methotrexate is inappropriate) and in combination with conventional DMARDs.  

Important Considerations and Potential Side Effects in the USA

While Xeljanz offers a valuable treatment option, it is a potent medication with a significant safety profile that requires careful consideration and monitoring by a healthcare provider, particularly in the USA where regulatory bodies have issued specific warnings.

Xeljanz carries several Boxed Warnings (the FDA's most serious warning), highlighting crucial risks:  

• Serious Infections: Xeljanz suppresses the immune system, increasing the risk of serious infections, including tuberculosis (TB), fungal, bacterial, and viral infections (e.g., shingles). Patients are typically screened for TB and hepatitis B before starting treatment, and monitoring for infections is ongoing. Live vaccines are generally avoided during treatment.  
• Increased Risk of Death in Certain People: Specifically, for adults aged 50 years and older with rheumatoid arthritis and at least one cardiovascular risk factor, Xeljanz (especially the 10 mg twice daily dose) has been associated with an increased risk of death compared to TNF blockers.  
• Major Adverse Cardiovascular Events (MACE): In the same patient population (RA patients 50+ with CV risk factors), there is an increased risk of serious cardiovascular events such as heart attack and stroke.
• Cancer and Immune System Problems: Xeljanz may increase the risk of certain cancers, including lymphoma, lung cancer (especially in current or past smokers), and non-melanoma skin cancer.  
• Blood Clots (Thrombosis): An increased risk of blood clots, including deep vein thrombosis (DVT) and pulmonary embolism (PE), has been observed, particularly with the higher dose (10 mg twice daily for UC) and in patients 50+ with CV risk factors.  
• Gastrointestinal Perforations: Though rare, tears in the stomach or intestines have been reported.  
• Laboratory Abnormalities: Increases in cholesterol and liver enzymes, and decreases in blood cell counts (lymphocytes, neutrophils, hemoglobin) can occur, requiring regular blood tests.  

Patients should discuss their medical history thoroughly with their doctor, including any history of infections, heart problems, stroke, blood clots, cancer, diverticulitis, or other chronic conditions.

Cost and Access in the USA:

Xeljanz is a high-cost specialty medication. Without insurance, a monthly supply can cost several thousand dollars. However, various programs are available to assist patients in the USA:  

• Insurance Coverage: Most commercial insurance plans, Medicare Part D, and some Medicaid plans cover Xeljanz. However, prior authorization is almost always required, and specific criteria (e.g., failing other DMARDs or TNF blockers first) vary by plan.  
• Manufacturer Savings Programs: Pfizer offers co-pay savings cards and patient assistance programs to help eligible commercially insured or uninsured patients reduce their out-of-pocket costs.  
• Pharmacy Discount Programs: While less impactful for specialty drugs, discount cards may offer some savings on the cash price.

Xeljanz represents a valuable oral option in the evolving treatment paradigm for moderate to severe rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis in the USA. Its targeted mechanism of action can provide significant relief for patients, but its use requires careful consideration of its safety profile and close monitoring by a rheumatologist to optimize benefits while minimizing risks.