Rheumatoid arthritis (RA) is an inflammatory autoimmune disease potentially leading to functional disability, with about 30% of patients unable to work after 3 years from the onset of symptoms. There is a growing realization that the host microbiota, and especially the gut microbiota, plays a key role in the development and progression of RA. There is also emerging evidence that different drugs, such as antibiotics and immunosuppressants, can influence and be influenced by the diversity and composition of microbiota in RA patients. However, data on the impact of microbiota in patients receiving immunosuppressive synthetic and biotechnological are still limited. The JAK family of enzymes (JAK1, JAK2, JAK3 and tyrosine kinase 2 (TYK2) are, important signaling molecules involved in a diverse range of biological functions such as the activity of inflammatory cytokines that play a critical role in RA. Currently there are three oral JAK inhibitors approved for the treatment of moderate to severe RA. Tofacitinib is the first of this new class of targeted synthetic DMARDs and is an inhibitor of the enzyme JAK1 and JAK 3. Baricitinib is a JAK1 and JAK2 inhibitor, finally Upadacitinib is the most recently approved and is a selective JAK1 inhibitor. This is the first study aiming at assessing the impact of JAK inhibitors in the variety and composition of the gut microbiota in RA patients and analyse correlations with clinical/serological parameters of drug effectiveness.Thirty RA patients will be enrolled in this prospective 6-months follow-up study. Disease activity will be evaluated by using the Disease activity score (DAS-28), Clinical Disease Activity Index (CDAI) and the simplified disease activity index (SDAI). Blood sample to analyse ESR, CRP, rheumatoid factor (RF), anticyclic citrullinated peptide antibodies (ACPA); sociodemographic as well as dietary and smoking habits will be also assessed the same day of clinical examination and stool sample collection.
In last years, several studies have pointed out a low diversity of gut microbiota and dysbiosis in patients with RA.
There is emerging evidence that different drugs, such as antibiotics and immunosuppressants, can influence and be influenced by the diversity and composition of microbiota in RA patients. However, data on the impact of microbiota in patients receiving immunosuppressive synthetic and biotechnological are still limited.
The JAK family of enzymes (JAK1, JAK2, JAK3 and tyrosine kinase 2 (TYK2) are, important signaling molecules involved in a diverse range of biological functions such as cytokine and growth factor signaling. Currently there are three oral JAK inhibitors approved for the treatment of moderate to severe RA. Currently there are three oral JAK inhibitors approved for the treatment of moderate to severe RA. Tofacitinib is the first of this new class of targeted synthetic DMARDs and is an inhibitor of the enzyme JAK1 and JAK 3. Baricitinib is a JAK1 and JAK2 inhibitor; finally Upadacitinib is the most recent JAK inhibitor approved in RA patients and is a selective JAK1 inhibitor.
This is the first study aiming at assessing the impact of JAK inhibitors in the variety and composition of the gut microbiota in RA patients and analyse possible correlations between the gut microbiota composition and clinical/serological parameters of drug effectiveness.