The role of JAK-inhibitors in the treatment of rheumatoid arthritis

Abstract

Introduction. Rheumatoid arthritis is a systemic chronic autoimmune inflammatory disease characterized by persistent destructive synovitis with extra-articular manifestations. Despite the recent development and recommended use of inhibitors of TNF and IL-6, as well as the B cell depletion of CD20 cells as remedies for RA, a large number of patients remain unresponsive and intolerable to these medications. JAK-inhibitors are the newest drugs with a targeted mechanism of action and promising clinical results. Aim of study. To elucidate the role of JAK-inhibitors as the long-term method and to evaluate the possible complications associated with this type of biological DMARD in order to identify clinically effective treatment for rheumatoid arthritis. Methods and materials. The scientific articles ranging from 2000-2022 published in PubMed, NCBI, BioMed Central databases, describing the nature and role JAK-inhibitors, the biochemical mechanisms and physiological effects were explored using key phrases “Janus-kinase receptors”, “JAK-inhibitors”, “rheumatoid arthritis”, “monotherapy”. Results. According to EULAR 2019 guidelines, JAK-inhibitors represents the 2nd line medication recommended in refractory to MTX monotherapy, moderate or high disease activity. Tofacitinib, an inhibitor of JAK1/JAK3, have shown response rates that were significantly higher compared to MTX monotherapy. The Tofacitinib + MTX combination was noninferior, establishing the same results as the standard adalimumab + MTX combination cure. Applying the modified van der Heije Total Sharp Score, the monotherapy with Tofacitinib overcame MTX monotherapy in limiting the progression damage. The blockage of IL-6 by targeting JAK-STAT3 induced by Tofactinib has diminished the pain within 24h. The published data show that frequent side effects of JAKinhibitors were the infections of upper/lower respiratory and urinary tracts, cytopenia being caused by JAK-inhibitors that act through JAK-2 pathway. Conclusion. The JAK-inhibitors have shown the same efficiency and safety profile as other types of bDMARDs. Oral administration, as well as early relief of pain prove JAK-inhibitors as promising treatment option increasingly used for proper medication of rheumatoid arthritis. characterized by persistent destructive synovitis with ex tra-articular manifestations. Despite the recent development and recommended use of inhibitors of TNF a nd IL-6, as well as the B cell depletion of CD20 cells as remedies for RA, a large numbe r of patients remain unresponsive and intolerable to these medications. JAK-inhibitors are the newest drugs with a targeted mechanism of action and promising clinical results. Aim of study. To elucidate the role of JAK-inhibitors as the long-term method and to evaluate the possible complications associated with this type of biolog ical DMARD in order to identify clinically effective treatment for rheumatoid arthrit is. Methods and materials. The scientific articles ranging from 2000-2022 published in PubMed, NCBI, BioMed Central databases, describing the nature and rol e JAK-inhibitors, the biochemical mechanisms and physiological effects were explored using k ey phrases “Janus-kinase receptors”, “JAK-inhibitors”, “rheumatoid arthritis”, “monotherapy ”. Results. According to EULAR 2019 guidelines, JAK-inhibitors represents the 2nd l ine medication recommended in refractory to MTX monotherapy, moderate or h igh disease activity. Tofacitinib, an inhibitor of JAK1/JAK3, have shown response rates that wer e significantly higher compared to MTX monotherapy. The Tofacitinib + MTX combination was n oninferior, establishing the same results as the standard adalimumab + MTX combination cure. Applying the modified van der Heije Total Sharp Score, the monotherapy with Tofacitinib ove rcame MTX monotherapy in limiting the progression damage. The blockage of IL-6 by targeting JAK-STA T3 induced by Tofactinib has diminished the pain within 24h. The published data show that fre quent side effects of JAKinhibitors were the infections of upper/lower respiratory an d urinary tracts, cytopenia being caused by JAK-inhibitors that act through JAK-2 pathway. Conclusion. The JAK-inhibitors have shown the same efficiency and sa fety profile as other types of bDMARDs. Oral administration, as well as early relie f of pain prove JAK-inhibitors as promising treatment option increasingly used for proper medi cation of rheumatoid arthritis.