Day 4 EULAR Report Save

The last day in London was exciting as both the Late-Breaking abstracts and new EULAR guidelines were presented. Guidelines presented addressed several significant unmet need areas including PMR, GCA, Takayasu’s arteritis, Vaccinations in Rheumatic patients, Imaging in spondyloarthritis and classification criteria for the Anti-Synthetase Syndrome. Here are but a few of my favorites from a list of many quality sessions.

• BE BOLD: Bimekizumab Beats Risankizumab (LB0001) – Merola et al presented the results of this landmark trial in PsA therapeutics — important as it is the first head-to-head (H2H) trial to show superiority of one drug in patients with active Psoriatic arthritis. 553 adults were randomized to either bimekizumab (BKZ, dual IL-17A and IL-17F inhibitor) or risankizumab (RZB, IL-23 inhibitor) at approved doses for 24 weeks. The primary endpoint was ACR50 at week 16 and BKZ demonstrated statistically superior joint outcomes (ACR60 of 49.1% vs 38% at week 16; p=0.0058). This advantage was maintained out to week 24 (55% vs 44%; p<0.0001). Interestingly, other secondary outcomes at week 24 may have numerically favored BKZ, but were not significantly different compared to RZB, including PASI100, DAPSA and MDA (Minimal Disease Activity). There were no new safety signals and Candida infections were more frequent with BKZ (none serious).
• RA-BRIDGE and RA-BRANCH: Increased VTE Risk with Baricitinib (LB009) -Peter Taylor presented the results from two large FDA post-marketing requirement (PMR) safety trials — RA-BRIDGE (global) and RA-BRANCH (US-only) — looking at the risk of venous thromboembolic events (VTE) comparing baricitinib (BARI) at 2 mg and 4 mg daily against TNF inhibitors (etanercept or adalimumab) in RA patients specifically enriched for VTE risk factors. A total of 3,640 patients were treated with either a TNF inhibitor or BARI 2 mg, or BARI 4 mg for up to ~6 years (11,524 patient-years. Patients were required to have at least one VTE risk factor (prior VTE, age ≥60, BMI ≥30, or age 50–59 with BMI 25–29). The primary endpoint was time to first adjudicated VTE, using a non-inferiority (NI) margin of 1.8 (upper 95% CI of HR). The trials closed early after 82 of 123 pre-specified VTE events were accrued. In the end, non-inferiority was Not Met – hence BARI was not non-inferior and had more VTE events (2.5%) versus TNFi (1.7%). The incidence rate was 0.79/100 PY for BARI combined versus 0.51/100 PY for TNFi. The hazard ratio was 1.606 (95% CI 0.969–2.660), with the upper CI exceeding the pre-specified NI margin of 1.8.  Neither BARI 2 mg nor BARI 4 mg met the NI margin of 1.8. No dose-dependent pattern was observed.  Unlike the Oral Surveillance study, baricitinib (neither dose) was associated with a higher risk of MACE (HR 1.06), all-cause mortality (HR 0.97), arterial thromboembolism (HR 1.27), or opportunistic infections (HR 1.25).  But serious infections were more frequent with baricitinib (IR 3.17 vs. 2.46/100 PY). These data reinforce the risk of VTE with JAK inhibitors but murky the concerns about MACE and cancer.
• Guidelines for PMR/GCA/TAK – were presented today. Such guidelines are long overdue as the last ACR/EULAR guidelines on PMR and GCA were in 2015.  Key takeaways from these 12 guideline recommendations include:
  • All patients with suspected PMR, GCA, or TAK should be referred to an appropriate specialist. Suspected cranial GCA demands urgent referral within 24 hours.
  • Glucocorticoid (GC) therapy should begin immediately if GCA is strongly suspected.
  • GC treatment can be deferred until diagnosis is confirmed in PMR and TAK.
  • Importantly, a trial of glucocorticoids should not be used as a diagnostic test.
  • For new-onset PMR, oral GC at 15–25 mg/day should be tapered to 10 mg/day within 1–2 months, aiming to stop within one year. Relapsing PMR requires GC escalation to at least the last effective dose with individualized tapering. New-onset GCA and active TAK both warrant 40–60 mg/day GC, tapered to 15–20 mg/day within 2–3 months, with a goal of GC discontinuation within 12–18 months.
  • For PMR, IL-6 receptor inhibitors (tocilizumab for new-onset; preferably sarilumab for relapsing/refractory disease) should be considered, with methotrexate as an alternative.
  • In GCA, tocilizumab or upadacitinib — now formally endorsed — should be considered particularly for refractory, relapsing, or GC-risk-prone patients.
  • All TAK patients should receive non-biologic DMARDs, with tocilizumab or TNF inhibitors reserved for refractory disease.
  • Relapse diagnosis in PMR and GCA relies on clinical and laboratory assessment supported by imaging; in TAK, imaging is central.
  • Refractory patients should undergo diagnostic re-evaluation and specialist center referral.
  • Elective vascular interventions in GCA and TAK should occur during stable remission, with urgent vascular referral for dissection or critical ischemia.
  • Routine monitoring across all three conditions should incorporate symptoms, clinical findings, and acute phase markers, with imaging used selectively for damage assessment in GCA and systematically in TAK.