Xeljanz alternatives: What can I take instead of Xeljanz?

Compare Xeljanz alternatives | Olumiant | Rinvoq | Otrexup | Humira | Enbrel | Natural alternatives | How to switch meds

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease that causes swelling and inflammation in affected parts of the body. In patients with RA, part of their immune system misidentifies healthy cells and attacks them. It most commonly attacks joints, such as those in the hands, wrists, and knees. Chronic inflammation will eventually cause permanent damage to the joint tissue, which can result in long-lasting pain and misshapenness. The treatment of RA can be challenging, both in identifying a regimen that provides relief and is tolerable to the patient, yet adequate management of this disease is crucial to preventing long-term damage as well as complications associated with RA. Possible complications include premature heart disease, obesity, and even depression, as the diagnosis directly impacts the quality of life. 

There are three very broad classes of drugs commonly employed as treatment options for rheumatoid arthritis: non-steroidal anti-inflammatory agents (NSAIDs), corticosteroids, and disease-modifying antirheumatic drugs (DMARDs). DMARDs can be further subclassified, and Xeljanz (tofacitinib) is a type of DMARD available for the treatment of RA that is either refractory to first-line DMARD therapy or taken due to intolerances associated with first-line therapy. NSAIDs and corticosteroids, like prednisone, only serve as a temporizing measure in symptom relief until DMARDs can be initiated because they do not prevent joint destruction, while DMARDs can. DMARDs, such as Xeljanz, come with many serious side effects that might cause a person to seek alternatives. Here we will discuss alternatives to Xeljanz in the management of rheumatoid arthritis. 

What can I take in place of Xeljanz?

The American College of Rheumatology (ACR) recommends a treat-to-target approach for patients with RA, meaning that patients should begin treatment as soon as RA is diagnosed to slow irreversible joint damage. Oral methotrexate remains the first-line treatment unless a patient can’t tolerate it or has a contraindication to it. Methotrexate is considered a conventional synthetic disease-modifying antirheumatic drug (csDMARD) that was developed without a specific target within the immune system, while biologic DMARDs (bDMARDs) are large molecules and highly specific to certain immune pathways. Targeted synthetic DMARDs (tsDMARDs) are also in contrast with methotrexate since they specifically target proinflammatory molecules and include the drug class known as Janus Kinase (JAK) inhibitors. These medications block the activity of the JAK enzyme, which plays a role in cytokine signaling that is linked to joint and tissue inflammation. Xeljanz is one example of a JAK inhibitor, but others do exist.

While Xeljanz is effective in the management of RA, it does come with side effects, some of which are serious, so awareness of more suitable alternatives for certain individuals is crucial in the creation of a treatment plan. 

Top 5 Xeljanz alternatives

The following are some of the most common alternatives to Xeljanz.

1. Olumiant (baricitinib)

Olumiant (baricitinib) is another JAK inhibitor. The typical dose is 2 mg once daily, and it is available in a tablet formulation, so can be taken by mouth. This is very convenient for patients. Like Xeljanz, patients taking Olumiant will need to have frequent blood work to monitor their lipid panel, liver function, and renal function. These medications may be held and restarted based on recommended monitoring parameters with bloodwork results. Both medications should be avoided in patients who are immunocompromised as dictated by low white blood cells, including lymphocytes. Similarly, the JAK inhibitors shouldn’t be combined with other immunosuppressive agents like azathioprine. This medication, like Xeljanz, would mostly be considered for moderately to severely active rheumatoid arthritis in patients who have had an inadequate response or intolerance to methotrexate. It can be used as monotherapy or in combination with methotrexate. 

2. Rinvoq (upadacitinib, extended-release)

Rinvoq is the third JAK inhibitor available for the management of RA. It is available in an extended-release formulation as a tablet, and the dose is typically 15 mg once daily. This medication, like its other JAK inhibitor counterparts, also requires blood work monitoring. Unlike Olumiant and Xeljanz, Rinvoq comes with many drug interactions. It is important to provide your healthcare provider with a complete list of your medications, including over-the-counter medications and supplements, so they can ensure serious drug-drug interactions don’t occur. Rinvoq, and all JAK inhibitors, also come with the risk of serious infections, thrombosis, or blood clots. It shouldn’t be combined with other JAK inhibitors or biologic DMARDs. 

3. Otrexup (methotrexate)

Otrexup, or oral methotrexate, is the first line DMARD selected for most patients with RA. If patients experience an inadequate response after three to four months of optimized methotrexate (meaning at least a 15mg dose once weekly), a different conventional synthetic DMARD may be tried or added, or a biologic DMARD or JAK inhibitor may be tried, or even added to Otrexup. Otrexup is considered the anchor drug for patients requiring combination therapy. The addition of or change to a biologic DMARD or JAK inhibitor is preferred over a historic approach known as triple therapy. Triple therapy includes a combination of hydroxychloroquine, sulfasalazine, and methotrexate or leflunomide in patients with an inadequate response to methotrexate. Newer agents, like brand name Xeljanz and other biologic DMARDs, may be more tolerable and have resulted in this triple therapy approach falling further out of favor; it may remain a cost-effective option for some patients since the biologic DMARDs and targeted DMARDs can be very costly. 

4. Humira (adalimumab)

Humira is an example of a biologic DMARD and is more specifically in the drug class known as Tumor Necrosis Factor (TNF) inhibitors. It is administered via subcutaneous injection every 2 weeks. While it is injectable, it can be self-administered so patients can do so in the comfort of their own homes, as opposed to going to their provider’s office or even an infusion center. Humira is immunosuppressing, so prior to initiation, patients may have to undergo extra testing to rule out certain infections, as well as be given appropriate vaccinations to minimize the risk of infections on therapy. In general, screening for hepatitis B, hepatitis B, and latent tuberculosis is recommended prior to initiating Humira, as reactivations of these infections can occur while on therapy. Receiving live vaccines while on Humira is also contraindicated due to its immunosuppressive effects. Humira can be used as monotherapy in the management of RA but is recommended to be given in combination with methotrexate for optimal efficacy. 

5. Enbrel (etanercept)

Enbrel is another example of a biologic DMARD as well as a TNF inhibitor that is administered via subcutaneous administration. Unlike Humira, it must be administered weekly as opposed to every 2 weeks. Enbrel may have a lower risk of serious infections in comparison to Humira, so may be a good option for patients concerned with those types of risks. TNF blockers also increase the risk of mild infections—the most common being upper respiratory tract infections, urinary tract infections, and skin infections. In some clinical trials with TNF blockers, malignancies like lymphoma were commonly observed compared to patients receiving a placebo. At this time, the Food and Drug Administration (FDA) has issued a black box warning for the use of TNF blockers and the risk of non-Hodgkin lymphoma (NHL). TNF blockers may also put patients at higher risk of other malignancies like non-melanoma skin cancer. While Enbrel can be used as monotherapy, it is also recommended in combination with methotrexate to yield the best outcomes. 

Natural alternatives to Xeljanz

Strategies to help manage an RA diagnosis include physical activity. Regular physical activity improves cardiovascular health and can reduce the increased risk of developing other chronic diseases associated with RA, such as heart disease, high blood pressure, diabetes, and depression. It also helps to maintain a healthy weight, which is important for bearing on joints that may be impacted. While management of RA will require prescription medications to prevent irreversible damage to joints, there is some research to support supplementation with natural products with anti-inflammatory properties providing some additional relief. Omega-3 fatty acids, which can be found in salmon and sardines, may have a protective effect due to their anti-inflammatory and modulatory effect on disease activity. Per clinical trials, moderate magnesium supplementation may also exert a protective role by inhibiting inflammatory responses. 

How to switch to a Xeljanz alternative

Anyone wanting to switch Xeljanz to an alternative should always do so under medical advice and in discussion with their healthcare provider. Unique situations—like pregnancy—may require abrupt discontinuation of Xeljanz, but this generally isn’t recommended out of concern for disease flair or recurrence. Discontinuation may be trialed after a period of low disease activity. Switching to alternatives may also happen when patients cannot tolerate the medication due to side effects or it starts to lose efficacy.