Day 2 Report - ACR Plenaries: Changing the Practice of Rheumatology Save

The Merriam-Webster definitions of “plenary” include: 1. complete in every respect: absolute, unqualified and 2. fully attended or constituted by all entitled to be present. Its Latin root plenus, means “full.”  Given the abundant offerings the ACR has, choosing a session to attend can be difficult and lead to decision paralysis. Over the years of navigating the annual meeting, I found the sessions with the most impact to my practice were the Plenary Sessions. During these sessions, the latest research is presented, new ideas are floated, and old myths debunked. They truly are well attended and make the meeting complete. The top ACR2023 Plenary abstracts I found impactful for my practice were:

• SGLT2 Inhibitors in SLE (Abstract # 1579) - This is an emulated study using a large US multicenter database evaluating the benefits of sodium-glucose cotransporter-2 inhibitors (SGLT2i) for systemic lupus erythematosus (SLE) and lupus nephritis (LN). SGLT2i has been found to reduce risk for major adverse cardiovascular events (MACE) and renal disease in non-SLE patients independent of hypoglycemic effects. SLE patients receiving SGLT2i (n= 426), or oral hypoglycemic agent comparator dipeptidyl peptidase 4 inhibitors (DPP4i) (n=865) were included. About a third of patients had lupus nephritis (LN). After adjusting for covariates (e.g., comorbidities, ACEi/ARB use), SGLT2i use was associated with lower risk for MACE (HR 0.69, 95% CI 0.48-0.99) and renal progression (HR 0.71, 95% CI 0.51-0.98). In patients with LN, SGLT2 use was also associated with less risk for MACE (HR 0.58, 95% CI 0.34-0.99), and trend for reduction in renal progression. Genitourinary infections were higher with SGLT2i compared to DPP4 (HR 2.32, 95% CI 1.45-3.72). Implications to my practice: Given the choice of a SGLT2 or DPP4 to manage diabetes in a SLE patient, I would recommend a SGLT2i.
• RA-ILD and TNF Inhibitors (Abstract #1582) - Previous reports raised alarm that tumor necrosis factor inhibitors (TNFi) may harm patients with rheumatoid arthritis interstitial lung disease (RA-ILD).  Veterans Health Administration (VA) study 1000+ patients with RA-ILD using a Target Trial Emulation framework with propensity score caliper-matched to compare active new users of TNFi to non-TNFi biologics or Janus kinase inhibitors (JAKi).  Primary outcome (3 years follow-up) and secondary outcome (1 year follow-up) assessed respiratory hospitalizations, respiratory deaths, and all-cause mortality.   No differences were seen between patients receiving TNFi and non-TNFi/JAKi regarding respiratory hospitalizations or deaths or all-cause mortality. Implications to my practice: NO need to avoid TNF inhibitors in RA-ILD.  It’s good to have options using TNF inhibitor, non-TNF biologic or JAK inhibitor in patients with RA-ILD. 
• SMART Study: Split-Dose Methotrexate (Abstract #1583) - This study evaluated whether split dose methotrexate (MTX) may have better efficacy compared to single weekly dose MTX.   This multicenter, randomized, controlled trial of 253 RA patients randomized patients to MTX 25 mg single dose qweek (n=128) vs. split-dose MTX (10 mg QAM, 15 mg QPM qweek; n=125). Patients were allowed to add leflunomide or sulfasalazine in week 16 if they had persistent disease activity.  The primary end point was a EULAR good response at 24 weeks.  At week 16, split dose MTX was superior to placebo (DAS28-ESR, ACR20, ACR50, ACR70) and patients were less likely to have to add another DMARD (35% vs 54.5%, p=0.005). There was a higher frequency of transaminitis in the split dose group compared to the single weekly dose group that had greater frequency of leukopenia.  Implications to my practice: Split dosing of MTX may be better for efficacy compared to single weekly dose; closer monitoring of liver enzymes may be needed with split dosing. 
• Prophylaxis in GPA (Abstract #1584) - This study evaluated effects of trimethoprim sulfamethoxazole (TMP-SMX) on infection risk for patients with granulomatosis with polyangiitis (GPA) taking rituximab (RTX).  A total of 919 patients were enrolled: 31% had TMP-SMX, 40% on prednisone >20 mg/day and were followed a median of 496 days. The rate for serious infections (SIE) was 6.1, for outpatient infections 28.7, and pneumocystis jirovecii pneumonia (PJP) 0.7 per 100 patient years (py).  SIE were related to pulmonary infections and general sepsis. TMP-SMX use was associated with lower SIE (aHR 0.5, 95% CI 0.3-0.8), outpatient infections (aHR 0.7, 95% CI 0.5-0.9), and PJP events.  Thirteen PJP infections (1%) occurred: all in patients not taking TMP-SMX.  Adverse events rates related to TMP-SMX use were 29.6 per 100 py compared to 13.4 per 100 py in those not on TMP-SMX.  Implications to my practice: The data indicates TMP-SMX can reduce serious infection, outpatient infections not just PJP in patients with GPA on RTX; unclear is how to balance potential benefits with side effects of TMP-SMX prophylaxis.