In recent years, the drug Xeljanz and its manufacturer (Pfizer) have come under fire due to side effects that Pfizer had not disclosed to the FDA, doctors, patients, or pharmacies. While they claim they were unaware of these side effects, the risk they present is real, regardless of if Pfizer knew about them or not. The FDA has placed its most prominent black box warning, which warns about the increased risk of blood clots and death.

With Xeljanz in hot water, other similar medications are also under scrutiny. The active ingredient in Xeljanz is tofacitinib. This ingredient falls under a class of drugs known as Janus kinase inhibitors (also referred to as JAK inhibitors). These inhibitors are disease-modifying antirheumatic drugs (DMARDs) and are often used to treat rheumatoid arthritis and other similar diseases.

However, after the FDA’s discovery, all JAK inhibitors are being carefully watched. Many people are not too familiar with these drugs. Knowing the history of JAK inhibitors and what they have been used for in the past will help you grasp the issues these drugs face.

Wormington & Bollinger understands how devasting it can be to suffer injuries after taking a prescription drug. No one expects a medication to do more harm than good. Unfortunately, many patients have suffered from the adverse reactions of Xeljanz. If you or a loved one sustained injuries while taking Xeljanz, contact our dangerous drug law firm today.

What are JAK Inhibitors? 

Before we dive into the history of JAK inhibitors, we should first take a moment to explain what they are and what they do. As we mentioned earlier, JAK inhibitors belong to a family of drugs known as disease-modifying antirheumatic drugs (DMARDs). The purpose of DMARDs is to modify the underlying disease instead of treating the symptoms.

For example, while pain killers provide pain relief, they do not treat or fix the issue. They only provide brief relief from the symptoms.

JAK inhibitors aim to reduce inflammation and swelling in the joints, which relieves joint pain and stiffness. That is why these drugs have become a popular method of treating rheumatoid arthritis (RA), psoriatic arthritis (PA), and ulcerative colitis (UC), all of which the FDA has approved Xeljanz to treat.

If you live with one of these conditions, it usually means you have an overactive immune system. Your body naturally produces proteins called cytokines, which it uses to help manage your immune system. Whenever your body detects an infection or inflammation, it increases cytokine production.

For those living with these conditions, their bodies produce too many cytokines than it needs. This overproduction leads to inflammation, joint stiffness, and pain. When your body releases these proteins, they attach themselves to receptors on immune cells. They then send a message to produce more cytokines, which increases inflammation.

JAK inhibitors interrupt this process by blocking the message pathways, thus preventing more cytokines from being made. These inhibitors help calm your immune system, which, in turn, reduces inflammation and pain.

The History of JAK Inhibitors 

The world is full of diseases, allergies, and even malignancies that create an imbalance in the body’s natural immune responses. Often, the activity of cytokines is the basis of these issues. After further research, more researchers began examining the alteration of cytokine functions in immune systems to create new solutions in research and drug development. Drugs targeting cytokines and their receptors have become the main tool in treating autoimmune disorders.

As more interest in cytokines and their functions grew, researchers quickly made advancements. Nearly 20 years ago, healthcare experts discovered Janus Kinase (JAK)-Signal Transducers and Activator Transcription (STAT) pathways. These pathways facilitate signaling between surface receptors and cellular responses. They also discovered that the four JAKs (JAK1, 2, 3, and TYK2) all play vital roles in cytokine-mediated effects.

Once they discovered these pathways, physicians used the success of specific kinase inhibitors to fuel their work in creating JAK inhibitors. Scientists began looking for ways to disrupt JAK signaling. However, the drugs that came before JAK inhibitors were unaffordable for most patients. Also, patients couldn’t take these drugs orally, and they had to be administered parenterally. And finally, in some cases (such as in RA patients), these drugs were ineffective.

All of this sparked the development of medications that could be taken orally and could help patients that found no success using biologics and other DMARDs. After years of research, the FDA eventually approved two JAK inhibitors, while many other drugs are in various stages of development and approval.

Approved Medications

The first JAK inhibitor the FDA approved was ruxolitinib in 2011. Ruxolitinib showed a preference for JAK1 and JAK2, which lent the drug to be an effective treatment for myeloproliferative diseases (MPD) patients. Ruxolitinib proved effective in treating myelofibrosis-related symptoms, with over 70% of patients showing overall clinical improvement over a 12-month period. The drug was successful in suppressing the amount of pro-inflammatory cytokines, as well.

Just like all drugs, ruxolitinib does come with side effects, most notably anemia and thrombocytopenia. However, these mainly occurred during the first few months of treatment. Doctors would reduce the dosage or discontinue the dose, among other things, to improve these adverse reactions.

The second JAK inhibitor the FDA approved was tofacitinib, the active ingredient in Xeljanz. The FDA approved tofacitinib as a treatment for rheumatoid arthritis first in 2012. Then they approved it for psoriatic arthritis in 2017 and ulcerative colitis in 2018. Recently, in September 2020, the FDA also approved the drug as a treatment for active polyarticular course juvenile idiopathic arthritis (pcJIA) in children and adolescents two years old and younger.

After over 20 years of research, healthcare professionals are learning more and more about JAK inhibitors. With the FDA’s approvals of ruxolitinib and tofacitinib, the door has opened for more inhibitors. As of this writing, there are several other drugs in various stages of development and approval, waiting to enter the market.

Contact Wormington & Bollinger

As you can see, the history of JAK inhibitors is still a relatively young one. With just a little over two decades worth of research, there is still much to learn about the effectiveness and safety of JAK inhibitors. As is the case with Xeljanz, there may be unknown side effects that threaten the lives of those taking it.

If you or someone you loved suffered injuries while taking Xeljanz, contact the experienced and knowledgeable dangerous drug attorneys at Wormington & Bollinger to learn what your options are.