Wednesday, 12 Dec 2018

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EULAR 2018 - Day 1 Report

Opening to a record attendance, EULAR 2018 started today with opening ceremonies that included the induction of honorary EULAR members:

  1. Jonathan Kay
  2. Jane Salmon
  3. Ronald van Vollenhoven
  4. Axel Finckh
  5. Marious Kouloumas
  6. Tadej Avcin

Highlights from the first day at EULAR included:

  • Canakinumab Prevents Acute Gout -  Dr. Dan Solomon presented a sub study (OP0014) of the CANTOS study that was published last year in the NEJM. In this study, Canakinumab was given to at risk cardiovascular disease patients, who did not have arthritis. IL-1 inhibition lead to a reduction in cardiovascular events and also reduction in cancer, especially lung cancer. The current abstracted looked at the influence of canakinumab on acute gout events in this very large cardiovascular population.  What they found was that the biologic lead to a 50-60% reduction in gout attacks. This was coupled with a significant drop in CRP levels, but no effect on serum uric acid levels. While many of the questions focused on the cost prohibitive aspects of such therapy in gout management, the overall message was that a significant reduction in systemic inflammation had multiple benefits – cardiovascular, cancer risk reduction and joint inflammation with less gout attacks.
  • AS Uveitis Benefits Most from TNF Inhibition (TNFi) - Dr. Ulf Lindstrom presented data from the Swiss database of 2577 Ankylosing Spondylitis (AS) patients and the effect of extra-articular comorbidities on clinical and therapeutic outcomes. Amongst their patients, 27% had anterior uveitis, 6% had psoriasis and 7% had inflammatory bowel disease (IBD). They found that having uveitis resulted in better biologic responses, with a 28% reduction in TNF discontinuations over nearly 10 years. On the other hand, the presence of psoriasis resulted in a 48% increase in TNFi discontinuations and IBD had no effect on TNF survival. They also looked at other comorbidities and found a similar effect as psoriasis, with higher rates of TNFi discontinuation‘s when the patient also had an affective disorder, lung disease, malignancy, diabetes and cardiovascular disease. They concluded that extra articular spondylarthritis manifestations and comorbidities may affect the long-term success of TNF blockade.
  • MRI Does Not Improve T2T or X-ray Outcomes -  IMAGINE-RA (OP0018)was an interesting study that looked at the value of adding MRI assessments to further guide treat to target (T2T) strategies in RA patients. This was a two-year prospective study that involved 200 RA patients who were CCP positive, with X-ray erosions, taking a DMARD, but were required to be in “Clinical remission” with a DAS-CRP < 3.2 and no swollen joints. Thus, patients started the study from position of already being in remission and thus were following them with maintaining remission, only adding on therapy when activity increased, using a pre-specified treatment algorithm. In the end there was no significant benefit to MRI on averting poor outcomes as the primary endpoint remission with a DAS28 < 2.6 was the same in the T2T and the T2T + MRI Groups.  Moreover both groups had the same x-ray progression. In my view they studied the wrong patients and did so with an expensive measure - MRI.
  • Baricitinib Wins in Lupus (SLE) - maybe?   The baricitinib in lupus study (OP0019) was presented by Dr. Daniel Wallace. The use of this Jak 1 & 2 inhibitor in lupus is based on the known effects of Jak 1 & 2 on interferon, IL-12, IL-23 and IL-6. This was a phase 2 trial that compared to placebo to baricitinib 2 mg for 4 mg given once daily in SLE patients who were required to be seropositive (ANA+, dsDNA+), have active disease with a SLEDAI-2K > 4 and no evidence of nephritis or cerebritis. Patients were also taking background steroids and immunosuppressives.  The primary endpoint was a reduction in SLEDAI-2K. This was only achieved by the 4 mg dose at week 24 (14% reduction vs PBO). The 2 mg dose did improve but not significantly. The safety profile of baricitinib in lupus was that similar to that seen in RA patients. In my opinion these benefits were fairly modest and only seen at the (unapproved) higher dose. In the USA, baricitinib is only approved at 2 mg qd for RA patients.
  • New Lupus Criteria – Dry Martin Arringer had the daunting task of presenting the new EULAR/ACR criteria for the diagnosis of lupus. After reviewing the 1998 and 2012 versions of the lupus classification criteria it was clear that the newer SLICC criteria improved the sensitivity but not the specificity over 1998 ACR (11 point) criteria.  The Delphi process and derivation and validation cohorts involved over 2000 patients lead to a set of weighted criteria that were tested against non-lupus controls, including RA, Sjogren’s, scleroderma, antiphospholipid and other autoimmune patients. In the end, an SLE diagnosis had to have an ANA greater > 1: 80 and then criteria that were weighted based on their strength of lupus association. Thus nephritis on biopsy having has the most number of points and oral ulcers having the least number.  The new criteria now significantly increased Sensitivity by 14% more than ACR 1998 criteria (Sensitivity ~ 96-98% and improved the specificity above the SLICC 2012 criteria by 6% (Specificity 93-96%). My problem with these new “tricked up” criteria is that in an effort to make these more exacting and more specific they’ve made these criteria impossible to use in the clinic setting as it will otherwise require an app or photographic memory to employ at the point of care.  If approved of by EULAR and ACR they will become a tool only be used in clinical trials but not clinical practice.
  • Lost Survival in RA – Dry Jeff Sparks brought this presentation to my attention. Widdifield and colleagues studied 2 different large Canadian RA populations and found RA increases mortality, but not initially so as it takes and average of 6 years for this difference to be apparent (OP0044) . Gap in survival was approximately 20% and started at 6 years vs matched population. At 10 years the adjusted mortality hazard ratios were 1.13 and 1.14 for British Columbia and Ontario.  These data call for more aggressive and early measures to avert the increased mortality risk seen with RA.

 

Disclosures: 
The author has received compensation as an advisor or consultant on this subject

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