Safety and Effectiveness of Tofacitinib in Treating Polyarticular Course Juvenile Idiopathic Arthritis.

Polyarticular course juvenile idiopathic arthritis (pcJIA) is a form of arthritis that affects at least five joints at a time and presents before the age of 16. Its most common symptoms are pain, swelling, redness, and a limited range of motion, making it incredibly difficult for patients diagnosed to function in daily life. Historically, the leading treatment options have consisted of non-steroidal anti-inflammatory drugs (NSAIDs) and disease-modifying antirheumatic drugs (DMARDs) such as methotrexate. However, these drugs have serious toxic side effects associated with long-term use in addition to being ineffective in refractory cases. Recently, small molecule biologics have emerged as an alternate treatment to pcJIA. Tofacitinib is a small molecule JAK inhibitor that blocks the JAK/STAT cascade and decreases the transcription of genes responsible for immune function. We conducted a risk-benefit analysis to determine the viability of tofacitinib as a treatment for pcJIA. In our review, we found the side effect profile of tofacitinib to be relatively mild, with many of the serious adverse side effects occurring in those immunocompromised and those with impaired renal and hepatic metabolism. Overall, we have determined that tofacitinib has the potential to be effective in reducing flare-ups and lowering erythrocyte sedimentation rate (ESR) in immunocompetent patients with pcJIA. Additionally, our review has found that tofacitinib has the potential to be effective in patients who are refractory to traditional treatment. However, large-scale clinical trials are needed to determine if this effect holds true in younger pediatric populations, as limited data surrounds this demographic.

Guselkumab, a Novel Monoclonal Antibody Inhibitor of the p19 Subunit of IL-23, for Psoriatic Arthritis and Plaque Psoriasis: A Review of Its Mechanism, Use, and Clinical Effectiveness.

Psoriatic arthritis and plaque psoriasis are autoimmune conditions affecting multiple organs, including the skin. The pathophysiology and etiology of these conditions are not fully understood; however, numerous factors are believed to play a critical role, including genetics and environmental risk factors. Furthermore, research suggests the IL-23/IL-17 pathway partially mediates these diseases. Once the IL-23 receptor is bound and activated, two subunits, p19, and p40, act through different signaling pathways. Ultimately, inflammation is produced through the effector molecule, IL-17, other cytokines, and tumor necrosis factor (TNF). Traditionally, these chronic conditions have been treated with TNF-α inhibitors and methotrexate, a dihydrofolate reductase inhibitor. Although successful in inhibiting the immune system, these drugs can have many adverse effects due to their broad targets. In recent years, more targeted therapy has become popular. Guselkumab is a monoclonal antibody that inhibits the p19 subunit of IL-23. It has been FDA-approved to treat both plaque psoriasis and psoriatic arthritis. Clinical trials showing guselkumab's efficacy have been promising, even showing improvement in symptoms of plaque psoriasis patients resistant to adalimumab, a TNF-α inhibitor. Guselkumab has also been shown to be well tolerated with a similar safety profile as other biologics inhibiting the immune system. In addition to its efficacy in treating plaque psoriasis and psoriatic arthritis, the mechanism of action offers a targeted approach that may minimize the broad immunosuppressive effects often associated with traditional therapies, providing a potential advantage in the long-term management of these autoimmune conditions.