JAK inhibitors or Janus kinase inhibitors are used to treat joint pain and swelling in patients suffering from rheumatoid arthritis. They are a new class of medications developed by researchers for patients whose rheumatoid arthritis is difficult to treat. They belong to the class of disease-modifying antirheumatic drugs (DMARD). In rheumatoid arthritis, the body’s immune system gets overactive and attacks the healthy cells in the lining of the joints and other organs of the body. JAK drugs work by suppressing the immune response helping prevent damage to the joints. JAK inhibitors potentially reduce the disease activity in people with rheumatoid arthritis, but the ultimate goal of the treatment is sustained remission.

What Is Rheumatoid Arthritis?

Rheumatoid arthritis is a type of autoimmune and long-standing inflammatory disorder that can affect one or more joints of the body. Some people might have problems in other body parts, including skin, eyes, lungs, heart, and blood vessels, due to rheumatoid arthritis. However, it mainly occurs when the immune system attacks the body's healthy cells. Rheumatoid arthritis must not be confused with osteoarthritis. In rheumatoid arthritis, the patient experiences a painful swelling in the lining of the joints, which eventually causes bone erosion and deformity.

What Are the Signs and Symptoms of Rheumatoid Arthritis?

In the initial stages, rheumatoid arthritis only affects the smaller joints, including the joints that attach the patient’s finger to his hands and toes to his feet. However, when the disease is left untreated at this stage, it progresses to other body parts, including the wrist, ankle, elbows, knees, hips, and shoulders. Sometimes, the symptoms might be noted in the same joints on both sides of the body. The signs and symptoms of rheumatoid arthritis are listed below:

The joints become tender, warm, and swollen.
The joints become stiff, and the condition becomes worse in the morning and after prolonged periods of inactivity.
Fever.
Tiredness.
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How Do JAK Inhibitors Work Against Rheumatoid Arthritis?

JAK inhibitors belong to the category of drugs called DMARDs. To date, the food and drug administration (FDA) has approved three JAK inhibitors which are listed below:

Tofacitinib.
Baricitinib.
Upadicitinib.

If a patient has been diagnosed with rheumatoid arthritis, his body makes the proteins known as cytokines in excess. These cytokines mediate an inflammatory response of the body tissues. These cytokines bind to the receptors present in the immune cells of the body like a key fits into a lock. When this happens, the body cells receive the message that they need to make more cytokines. This is the point when the JAK inhibitors come into action. They hinder this inflammatory procedure and ease the symptoms of rheumatoid arthritis. These JAK inhibitors directly interfere with the production of cytokines and interrupt their signaling pathways. However, as per the researchers, JAK inhibitors are not effective against all the cytokine molecules and might not provide many benefits to some individuals. They just limit the progression of rheumatoid arthritis rather than removing the root cause of the problem.

What Has Been Known About the Efficacy of JAK Inhibitors Against Rheumatoid Arthritis?

The study reports that these drugs have been found to be effective and relatively safe for treating moderate to severe rheumatoid arthritis. Some researchers indicate that JAK inhibitors are more effective than Adalimumab and other drugs of the same class. According to the clinical trials conducted in 2017 and 2019 to evaluate the safety and efficacy of JAK inhibitors, it was discovered that people who took these drugs showed 20 % improvements in the key symptoms of rheumatoid arthritis. This proves that JAK inhibitors are effective for the ones who have not responded well to other treatments. However, more relevant studies and clinical trials are needed to evaluate the safety and efficacy of JAK inhibitors.

What Has Been Known About the Safety of JAK Inhibitors in Rheumatoid Arthritis?

JAK inhibitors are the new drugs that have been launched in the market, so not much is known about the safety of JAK inhibitors. However, the studies suggest that they pose risks similar to other drugs of the same class. The study report published in 2020 concluded that the safety profile of JAK inhibitors is consistent with the other biological drugs used to treat rheumatoid arthritis. JAK inhibitors are basically immunosuppressant drugs associated with an increased risk of severe and opportunistic infections. Some people might develop herpes zoster infection after taking JAK inhibitors. However, a clinical trial reported that the risk of herpes infection in people taking JAK inhibitors is less than in those taking other drugs.

What Are the Different JAK Inhibitors?

JAK inhibitors have gained much popularity over the past few years because of their targeted mechanism of action and oral delivery route. However, the biggest dilemma associated with the drug is the risk of herpes zoster infection. The different JAK inhibitors approved by the FDA are listed below:

Tofacitinib - It was the first JAK inhibitor that was launched in the market to treat rheumatoid arthritis. Tofacitinib 5 mg was approved by the FDA to be taken twice a day. This drug is effective for people suffering from moderate to severe arthritis who have had an inadequate response or did not benefit from other drugs. The studies have reported that the Tofacitinib and Methotrexate combination is more effective than Tofacitinib alone.
Baricitinib - Baricitinib has been specifically approved for the management of active rheumatoid arthritis. It directly inhibits the Janus kinase enzymes involved in the inflammation and symptoms of rheumatoid arthritis. During the clinical studies, it was noted that Barictinib was superior and far better than the other drugs in treating rheumatoid arthritis.
Upadacitinib - Upadacitinib has been shown to have a better safety profile than Baricitnib and Tofacitinib. It has to be taken once daily, but the drug demonstrated low disease activity and high remission rates when administered to the patients in the clinical trial.

Who Benefits the Maximum From JAK Inhibitors?

Some people might not need JAK inhibitors because older drugs like Adalimumab and Methotrexate help control their symptoms of rheumatoid arthritis. However, the old drugs might not be suitable and efficacious for everyone. It has been noted that 65 % of patients who take DMARDs get relieved from their symptoms. If the person taking the drug belongs to the group of these 65 % people, then DMARDs are definitely of great help. One of the studies noted that more than half of the people who did not see improvements in their symptoms after taking the biological drugs, their symptoms became less severe after taking a JAK inhibitor for three months. The biggest advantage of the JAK inhibitors is that they can be taken orally, unlike the other biologic drugs like Adalimumab that need to be injected into the skin.

What Are the Side Effects of JAK Inhibitors?

As JAK inhibitors interfere with the working of the immune system, they might leave the patient vulnerable to infectious diseases. In addition, the following side effects have been noted to date:

During a clinical trial, it was observed that people who took Tofacitinib presented with severe respiratory diseases like tuberculosis.
The risk of herpes zoster also increases after taking JAK inhibitors. However, the drugs have a short half-life meaning that the patient’s immune system will return to normal after he stops taking these drugs.
Some patients might suffer from anemia after taking JAK inhibitors because they directly affect the protein required to make red blood cells in the body.
JAK inhibitors can reduce the white blood cell count also.
These medications can elevate the cholesterol levels of a person. However, the levels can be brought back to normal by taking statin drugs.
Some doctors are concerned that the patient might be at risk of developing cancer because this drug reduces the immune system’s ability to fight the tumor cells.
People suffering from cardiac diseases might show the formation of blood clots after taking these drugs.

Conclusion:

JAK inhibitors are revolutionary drugs in managing rheumatoid arthritis because they directly act on the immune system and stop the progression of the disease. Therefore, they are a boon for the ones suffering from rheumatoid arthritis for prolonged periods who have not responded well to other medications or treatments. Though many side effects are associated with JAK inhibitors, the patient must not get worried as the immune system returns to normal once he stops taking these drugs. Therefore, people suffering from untreated rheumatoid arthritis for prolonged periods must seek medical attention at the earliest to learn more about the JAK inhibitors and their benefits.