Baricitinib for systemic lupus erythematosus

We read the study on the therapeutic benefit of baricitinib for systemic lupus erythematosus by Daniel J Wallace and colleagues (July 21, 2018, p 222)1Wallace DJ Furie RA Tanaka Y et al.Baricitinib for systemic lupus erythematosus: a double-blind, randomised, placebo-controlled, phase 2 trial.Lancet. 2018; 392: 222-231Summary Full Text Full Text PDF PubMed Scopus (289) Google Scholar with great interest. However, we raise concerns about the safety of a once-daily 4 mg dose of baricitinib. The Article indicates that the rates of serious infections were higher in the group receiving 4 mg baricitinib, compared with the groups receiving 2 mg baricitinib or placebo. The appendix revealed the proportion of patients with decreased neutrophil counts (<2000 per mm3) was higher in the group receiving the 4 mg dose (27·6%) than in the groups receiving the 2 mg dose (15·2%) and placebo (16·2%). 4 mg of baricitinib also increased lipid parameters and serum creatine phosphokinase. In June, 2018, the US Food and Drug Administration (FDA) approved a once-daily dose of 2 mg baricitinib for the treatment of adult patients with moderately to severely active rheumatoid arthritis.2Mullard A FDA approves Eli Lilly's baricitinib.Nat Rev Drug Discov. 2018; 17: 460Google Scholar However, the FDA did not approve a 4 mg dose because of safety concerns including serious infections and thromboses. Baricitinib is a selective inhibitor of Janus kinase 1 (JAK1) and Janus kinase 2 (JAK2). Although JAK1 and JAK2 are involved in the pathogenesis of autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus, they are very important in innate immune antiviral responses and tumour surveillance. JAK1 and JAK2 are pivotal kinases mediating the downstream signalling of type 1 and type 2 interferons as well as many kinds of interleukins.3O'Shea JJ Schwartz DM Villarino AV Gadina M McInnes IB Laurence A The JAK-STAT pathway: impact on human disease and therapeutic intervention.Annu Rev Med. 2015; 66: 311-328Crossref PubMed Scopus (827) Google Scholar STAT1 has an important role in the JAK-STAT signalling pathway, and loss-of-function mutations of STAT1 confer susceptibility to mycobacterial and viral infections.4O'Shea JJ Holland SM Staudt LM JAKs and STATs in immunity, immunodeficiency, and cancer.N Engl J Med. 2013; 368: 161-170Crossref PubMed Scopus (568) Google Scholar In conclusion, overall benefit-risk assessment, especially for the 4 mg dose of baricitinib to treat systemic lupus erythematosus, should be discussed further. We declare no competing interests. Baricitinib for systemic lupus erythematosus: a double-blind, randomised, placebo-controlled, phase 2 trialThe baricitinib 4 mg dose, but not the 2 mg dose, significantly improved the signs and symptoms of active systemic lupus erythematosus in patients who were not adequately controlled despite standard of care therapy, with a safety profile consistent with previous studies of baricitinib. This study provides the foundation for future phase 3 trials of JAK1/2 inhibition with baricitinib as a new potential oral therapy for systemic lupus erythematosus. Full-Text PDF Baricitinib for systemic lupus erythematosus – Authors' replyWe thank Kai Yuan and colleagues for their interest in this trial.1 The results from the phase 2 trial informed the baricitinib systemic lupus erythematosus phase 3 programme, including dose selection. We agree that additional data are required to better characterise and establish the overall benefits and risks related to a 4 mg dose of baricitinib. Therefore, we are carrying out a more extensive benefit–risk assessment in the ongoing baricitinib phase 3 global systemic lupus erythematosus programme ( ClinicalTrials.gov , numbers NCT03616912 and NCT03616964 ). Full-Text PDF