Letter from the Editor

Dear Reader,

The EULAR meeting in Amsterdam in June 2018 brought together over 14,000 medical doctors, allied healthcare professionals, and scientists. The transformative effect of the introduction of biological therapies and their positive long-term, and still emerging, legacy is being increasingly appreciated. Robust evidence showed that rheumatologists “doing their thing” and treating rheumatoid arthritis effectively and early, has benefits beyond the joint, namely the significant long-term reduction of cardiovascular complications. The normalisation of mortality in relationship to the general population raises important issues as to whether rheumatologists need heightened vigilance for cardiovascular complications, especially in well-treated patients.

Drug cost rationalisation with the introduction of biosimilars and both conventional and biological DMARD tapering strategies are ongoing areas of research in RA. The latest evidence supporting the safety of biosimilars is reviewed and studies comparing either conventional or biological DMARD tapering in RA subjects indicated that in the region of 40% of cases relapse at 1 year irrespective of which class of drug was stopped first. It remains to be determined whether longer term tapering strategies will lead to “seesaw” disease control in the face of lower drug costs. Despite the great therapeutic successes in RA, the clinical reality is that many patients remain difficult to treat; a debilitating and heart sink scenario for the patient and doctor. A large international survey addressed this issue and defined fatigue, 2 or more DMARD failures, and moderate corticosteroid dose usage as parameters that experts view as defining this situation. This will certainly be a space to watch in the coming years, especially when these parameters are stacked against hard objective evidence of ongoing inflammation including swollen joint counts and laboratory or imaging evidence of active inflammation.

A link between obesity and psoriatic arthritis is well defined and while recent RA studies are less clear, they suggest a link with antibody negative disease; possibly pointing towards mechanistic overlaps with PsA in this RA subgroup. Therapeutic refinements in RA included data on the introduction of only the second anti-IL-6R monoclonal therapy to practice, the demonstration of anti-TNF drug levels and infection risk and the reassuring long-term safety of anti-TNF agents. In spondyloarthritis, emergent evidence suggests that vedolizumab, an integrin blocker with efficacy in IBD, may be ineffective in those cases with concomitant arthritis and even associated with new onset arthritis. These observations were made in cases that generally had previously failed an anti-TNF for IBD. It is interesting to note that this is the diametric opposite of etanercept and anti-IL-17A therapies that are effective for arthritis but not for IBD. Data presented at EULAR also had the pendulum swinging in favour of anti-TNF plus celecoxib in being more effective in preventing new bone formation in cases of ankylosing spondylitis. On the same topic of bone biology, low bone mineral density as a potential detrimental factor in early SpA was also highlighted. Specifically, in the case of psoriatic arthritis, long-term extension from phase 3 clinical trials showed the continuing benefit of PDE4 inhibition. The generally beneficial effect of the licenced PsA agents on HAQ-DI was also reported, with this particular parameter being considered important on the patient’s quality of life.

For those rheumatologists with a particular interest of focus on osteoporosis and osteoarthritis, several interesting areas were covered. One study looked at factors including vitamin D insufficiency and low bone mineral density in axial SpA. Experimental models also showed the role for microRNAs in osteoporosis, which could be potentially exploitable therapeutically in the future. Outcome measures for therapy optimisation are lacking in osteoarthritis. We cover interesting animal model and human data showing how glucosepane, an advanced glycation end-product, may have a role in osteoarthritis monitoring.

In the case of the autoimmune connective tissues diseases, new classification criteria were revealed for SLE. Early evidence for response to baricitinib in SLE was also provided and fits well with the role of the JAK/STAT pathway in regulating type-1 interferon cytokine pathways in disease. Another study showed that ustekinumab, an IL-12/23 blocker, also showed promise in SLE. IL-12 regulates gamma interferon, which was considered a less important interferon family member in SLE, and recent murine studies have also incriminated IL-23 in disease. The phase 3 trial programmes with their bumpy SLE outcome measures awaits these agents. Emergent strategies for the treatment of systemic sclerosis was also discussed, including the repurposing of anti-fibrotic therapies from the idiopathic pulmonary fibrosis arena and also the use of rituximab, a drug with an impressive record in most autoantibody associated diseases with the possible exception of Sjögren’s syndrome.

I sincerely hope that this brief distillate of the foregoing commentaries in recent developments in rheumatology highlights from EULAR will whet your appetite for a very enjoyable read. We hope that this document will keep your curiosity for the rheumatic diseases alive and well until we see you in the bustling educational environment of EULAR in Madrid in 2019 for the next installment.

Best regards, Prof. Dennis McGonagle

Biography

Dennis McGonagle, FRCPI, PhD, is an Academic Rheumatologist at the University of Leeds and section head of Experimental Rheumatology. He graduated in Medicine from the University College Dublin in 1990 and undertook postgraduate training in Dublin and Leeds where he completed his PhD. He has developed the modern enthesitis model for spondyloarthropathies and psoriatic arthritis including the cytokine mediated enthesis originating theory of disease (Lancet 1998). He also described the synovio-entheseal complex, nail anchorage to the skeleton, developed an integrated biomechanical and immunology model for PsA, and a mechanistic disease classification of immune diseases (PLoS Med 2006). His group also discovered synovial fluid mesenchymal stem cells, which is being researched towards osteoarthritis therapy development. Prof. McGonagle has also served on the EULAR scientific committee and is a member of the Editorial Board of ARD.



Posted on 24 August, 201829 March, 2021