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JAK Inhibitors. What do these drugs add to the Covid-19 therapy pool?

JAK Inhibitors. What do these drugs add to the Covid-19 therapy pool?

JAK inhibitors, drugs previously reserved for conditions like rheumatoid arthritis, have shown promising results in ameliorating the disastrous effects of Covid-19.

We now know, with certainty, that a dysregulated immune response due to Covid-19 drives the severity of the disease. The surge in pro-inflammatory molecules that entail the cytokine storm is key to disease progression and its complications. All research into the possible therapeutic regimens for this enigma has almost centred around the trial of all potential drugs that modulate the body’s immunity. The Janus Kinase (JAK) inhibitors did not escape the radar. They have, however, delivered promising results that have garnered attention to them being critical adjunct therapeutics to the ever-growing Covid-19 treatment protocol. But what do the JAK inhibitors add to this pool?

Since the first case of SARS-COV-2 in Wuhan, China, clinicians have endeavoured to understand the mechanisms underlying disease progression in some individuals afflicted with Covid-19 as a vast majority of patients are either asymptomatic or present with mild disease. Scientists have highlighted several risk factors, and they all have a pivotal point – they tend towards a dysregulated immune response to the infection.

As the body attempts to curb the deleterious effects of Covid-19, immune response leads to the generation of several inflammatory molecules – cytokines and chemokines like interleukins-2, 6, and 10; interferon-gamma, tumour necrosis factor-alpha, granulocyte-macrophage colony-stimulating factor, among others. These cytokines interact with other intra-and extracellular molecules along the different pathways to cause the inflammatory cascade we’ve observed among patients with Covid-19. Among those pathways, the JAK/STAT pathway plays a pivotal role to anchor the cytokines onto their receptors and leading to a potentiation in their synthesis and thus more inflammation. JAK inhibitors specifically, those that are selective for JAK1, JAK2, and JAK3, might curb the inflammatory effects by inhibiting the elevated signalling cytokine pathways, improving the lymphocyte counts, and acting against SARS-CoV-2, thus limiting disease progression and leading to faster recovery.

Three JAK inhibitors: Tofacitinib, Baricitinib, and Ruxolitinib – have had promising efficacy in ameliorating the effects of Covid-19 and thus, reducing mortality among these patients. The trio has extensive immunomodulatory effects on the body that halt the progression of Covid-19 by curbing the inflammatory cascade observed in the cytokine storm. And their safety profiles are within acceptable margins.

The JAK inhibitors don’t just increase the pool from which clinicians can choose to treat patients with SARS-CoV-2 pneumonia. They provide potential opportunities and much-needed avenues to reduce mortality within the hospitalised patients. Ground-breaking therapeutics have included low-dose dexamethasone, remdesivir, and tocilizumab, among others.

Important to note is the cost of these medications. Unlike Tocilizumab, Tofacitinib, Baricitinib, and Ruxolitinib are relatively affordable. Besides, we can administer them orally. Also, they have been in existence as some of the drugs we use in managing immune-mediated disorders like rheumatoid arthritis.  And more clinical trials are ongoing to ascertain their efficacy in many similar diseases. Covid-19 is just the latest addition.

IAmDrSsekandi

MBChB (MUK), Graduate Fellow, Department of Physiology, Makerere University Founder and Content Creator Peer reviewer, Associate Editor

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