I would like to take this opportunity to thank the ORADE grant committee for providing me the opportunity to attend the 2019 Congress of Clinical Rheumatology. This was as a five day congress highlighting recent advances in everything from the basic sciences to new clinical paradigms. Below is a summary of major highlights from the congress.
Immunology for Rheumatology Providers: A Disease-Based Approach.
The first day of the congress entailed a focus on immunology and covered the immunology and immunologically targeted treatment of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and lupus. A highlight from this session was the presentation by Dr. Leonard Calabrese discussing rheumatic immune-related adverse events from cancer immunotherapy as well as his highlights of basic and clinical immunology. This is an area that we as rheumatologists need to be heavily involved in as in 2018 there were over 900 new cancer immunotherapies in development, over 5000 clinical trials and some estimates suggest that the market for PD-1 and PD-L1 inhibitors could reach $120 billion. Dr. Calabrese highlighted the many rheumatic presentation of immune mediated adverse events including arthralgia, inflammatory arthritis, connective tissue disease and myositis. Management for these adverse events can be complex but generally follows the paradigm of Grade 1 reactions being observed, Grade 2 events warranting symptomatic therapy as well as low dose glucocorticoids. Grade 3 events warrant referral to subspecialist care (Rheumatology, Endocrinology, GI, Respirology etc.), holding of the immune checkpoint inhibitor and initiation of IV glucocorticoids. If unable to taper the steroids to less than 10-20mg OD consideration should be made for initiation of DMARDS. Grade 4 events, warrant consideration for advanced immunosuppression such as TNFi, anti-IL-6 etc. (Puzanov et al. J Immunother Cancer 2017 Nov 21;5(1):95.) Despite the issues created by immune related adverse events, these irAEs may in fact be predictive of a response against cancer (Kostine M. et. Al. EULAR 2017, oral presentation OP88, 13 June 2018).
The Intestinal Microbiome and Rheumatic Disease presented by Dr. James Rosenbaum highlighted the intriguing world of the microbiome and its role in the development of rheumatic diseases. This area remains a fascinating and mysterious one as 99% of the transcripts expressed in the body are derived from microbes and only a fraction of the microbial world that we host is easily cultured. Dr. Rosenbaum posed to the audience “Do HLA molecules shape the microbiome?”. He then presented the paper from Olivares et al. showing that the HLA-DQ2 genotype selects for early intestinal microbiota composition in infants at high risk of developing celiac disease (Olivares M. et al. Gut 2015 Mar;64(3):406-17). He proposed that HLA-B27 alters the microbiome subsequently altering gut permeability, triggering the immune response and ultimately leading to spondyloarthritis and uveitis. Mechanistically, how could this occur? Dr. Rosenbaum presented a paper by Morton et al. wherein Kaede transgenic mice were used to track leukocyte movement to and from the gut. The endoscopic approach used by the team allowed them to track gut-derived Th17 cells in the spleens of these mice at the onset of their genetically determined arthritis thus suggesting a mechanistic link between the intestinal microbiota and extraintestinal inflammatory disease (Morton et al. Proc Natl Acad Sci USA. 2014 May 6;111(18):6696-701). Dr. Rosenbaum then presented work demonstrating lymphocyte trafficking between the gut and the eye. Therapeutic implications abound as one ponders the role for restoration of the underlying intestinal homeostasis via targeting microbial metabolism, altering barrier function, probiotics, diet, prebiotics and antibiotics (Nat Rev Rheumatol 2018 Dec;14(12):704-713).
Difficult Scenarios in Biologic Use presented by Dr. Jack Cush took the attendees through various clinical vignettes highlighting cases such as the reluctant patient, those with recurrent infections and the perioperative/post-operative patient. A key take home message from this presentation as the use of the RABBIT risk score for infection. This tool can be accessed at www.biologika-register.de. Features of this risk score include age >60, HAQ, severe infection in the past 12 months, COPD/lung disease, CKD, number of prior DMARDs, steroid dose, current biologic use. Dr. Cush reviewed seasonal flu vaccination in our RA patients on MTX. As described my Park et al. temporary discontinuation of methotrexate for two weeks after vaccination improves the immunogenicity of seasonal influenza vaccination in RA patients and importantly did not increase RA disease activity (Park et al. Ann Rheum Dis 2018 Jun;77(6):898-904). Also highlighted was the high dose influenza vaccine study performed at McGill and presented at the ACR in 2018. This study randomized RA patients to standard dose and high dose quadrivalent flu vaccine with primary endpoint being seroconversion at day 28. This study showed that those RA patients receiving the high dose vaccine had a 2-3 fold higher seroconversion rate. Important to note, however, is the increased cost of the quadrivalent vaccine. Dr. Cush ended with some of his personal thoughts on “Safety Rules to Live By”. These include: The longer you’re on the drug; the safer it becomes, Lower doses are NOT always safer, the safe thing to do is to KNOW and accept the risks.
In conclusion, attending the 2019 Congress of Clinical Rheumatology was an invaluable experience for me as a rheumatologist in my first year of practice. The congress covered a host of important principles and advancements in the field as well as offered insight into where future discoveries are being pursued. I would like to thank the ORADE committee for supporting my attendance at this premier meeting.