Opening Day Report Save

The opening of ACR2 Convergence was a hit for all who signed up and viewed in. The day included the presidential address by outgoing president Dr. David Karp (UT Southwestern) and a keynote talk and interview with Dr. Seema Yasmin (Stanford).

The Year in Review featured a clinical vs basic science Brigham and Women’s Hospital faceoff between its two faculty, Dr. Karen Costenbader and Dr. Michael Brenner.

Dr. Brenner presented his choice in scientific advances in the last year, specifically focusing on impactful basic science original research in the last year. He did a masterful job introducing each scientific advance, the background and evidence and the potential clinical or therapeutic implications. Here are the citations they presented:

Dr. Michael Brenner (Basic Science Advances)

1. Nobel prize research on how IL-1 results in chondrocyte hypersensitivity to mechanical loading and its relevance to osteoarthritis (OA): IL-1 upregulates Piezo 1 that is part of mechanosensitive ion channels. Citation: https://bit.ly/3EMQFU2
2. Ubiquitin (UBS) related somatic mutation and VEXAS – this syndrome was rolled out at ACR2020 and defines an X-linked UBA1 mutation leading to an adult autoinflammatory syndrome called VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic). The syndrome has an adult onset and presents with fevers, cytopenias, vacuoles in myeloid and erythroid precursor cells, dysplastic bone marrow, neutrophilic cutaneous and pulmonary inflammation, chondritis, and vasculitis. Citation: https://bit.ly/3o3OkND
3. RBC retained mitochondrial DNA triggers type I interferon (IFN) signaling in lupus (SLE). This work from Dr. Virginia Pascual’s group shows that mDNA may drive as much as 40% of the type I IFN production that drives B cells and the humoral response. Moreover, these investigators show how mDNA levels correlate with clinical activity and severity in lupus. Citation: https://bit.ly/3mPsLkC
4. IFN Autoantibodies are present in Life-Threatening COVID-19 infection (but not present in those who fair well). Nearly 10% (101/987) of life-threatening COVID-19 pneumonia patients had neutralizing auto-Abs against IFN-ω or IFN-α or both. Moreover, this finding was uniquely higher in men than women (12.5% vs 2.6%) and tend to increase with age. Targeting their production maybe therapeutically exploited in sick COVID-19 patients. The title of this Science article was  Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths Citation: https://bit.ly/3wsB0GE
5. Noninflammatory mRNA in EAE and how it could be used therapeutically to induce immune tolerance. Citation: https://bit.ly/3k5BUUv
6. CRISPR gene edited stem cells inserted into cartilage implants that can sense milieu changes (e.g., inflammation) and deliver targeted drug therapy (e.g., anticytokines, IL-1RA, etc.) to control inflammation and damage locally. VERY COOL SCIENCE! Citation: https://bit.ly/3CTvxe8

Dr. Karen Costenbader

1. Avacopan (C5a inhibitor) in ANCA-Associated Vasculitis: a lot of discussion about its safety (same AE rates as the steroid comparator), efficacy (it failed to meet its primary endpoint; FDA panel voted against its approval) and very high annual cost (>$150,000). Citation: https://bit.ly/3kbpbzE  nejm.org/doi/full/10.1056/nejmoa2023386
2. AURORA1 Trial – voclosporin in lupus nephritis. FDA approval as add-on therapy (to MMF, AZA, etc.) on biopsy proven (class III/IV) lupus nephritis. The drug outperformed placebo (41% vs 23 % CRR). Citation: https://bit.ly/3CPoh2R
3. Tofacitinib Efficacy in Ankylosing spondylitis. Published in ARD by Deodhar et al. Tofa was shown to be effective vs placebo in active AS patients with ASAS40 responses of 40.6% vs 12.5%, at week 16. Citation: https://bit.ly/3bN16dG
4. 1133 Oral Surveillance study: the benefits of JAK inhibition (see above) need to be assessed against the results of the 1133 study that will be presented throughout this meeting – there are concerns and now boxed warning for tofacitinib, upadacitinib and baricitinib cardiovascular and lymphoma risks with JAK inhibition (stay tuned)
5. ARCTIC Rewind study:  shows the clear superiority of continuing effective (LDAS) DMARD and biologic therapy over cutting to a half dose; results showing a much higher flare risk with half dose drug therapy. Citation: https://bit.ly/3wm1bi1
6. TICOSPA study: does tight control work in spondylarthritis patients? According to this study no, but the problem may have been the function primarily endpoint (ASAS-HI) as opposed to other T2T trials that use a disease activity endpoint (e.g., ASAS40, ASAS20, BASDAI). Citation: https://bit.ly/3ESdZzB
7. Benefits seen in the RCT: Stepped Exercise Program for Patients with Knee Osteoarthritis – yes it works! Citation: https://bit.ly/2ZW73T0
8. Comparison of two trials of IVIG in MIS-C related to COVID – a US study  vs the international (BAT) study