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Fever Pitch (7.15.2022)

Jack Cush, MD

Dr. Jack Cush reviews the new studies and drug approvals and new insights into febrile disorders from the past week on

  1. Ustekinumab (IL-12/23i) phase 2 study was successful in #SLE; but the phase 3 LOTUS study of 512 pts, UST was NOT superior to PBO (SRI-4 44% v 56%) at 1 year. Study was halted for lack of efficacy (but no safety concerns).

  2. MTX + Pegloticase Combo FDA Approved Horizon has announced that the FDA has approved the expanded labeling of pegloticase (Krystexxa) injection to be co-administered with methotrexate (MTX), to improve response rates in patients with uncontrolled gout.

  3. N.Zealand adult registry of ~1million without CV disease, amongst whom 32K had gout. Having gout increased risk of CV events in women (adj HR 1.34;1.23-1.45) and men (1.18). CV risk in men was increased if not on ULT & not at target (~15%)

  4. Should Physical exercise be recommended in dermatomyositis and polymyositis: a systematic review of 19 studies and 298 patients showed significant improvements in strength & aerobic capacity without change in CK levels or exacerbations

  5. 1 yr success of knee arthroplasty was drawn frm 20 studies (11 317 pts, 37 factors) suggests higher BMI was correlated w/ worse physical function. Physical function & OA severity assoc. w/ better function post-TKA

  6. Viscosupplementation Ineffective in Knee Osteoarthritis

  7. French registry of IBD due to IL-17 inhib revealed 32 pts- risk of new IBD was low & decreased 2016 to 2019, w/ good outcome in 24/31. IBD more common w/ AS (27) vs PsO (4), IBD onse after 4 (1.5–7.5) mos; all cases w/ secukinumab

  8. SELECT-AXIS 1 trial of upadacitinib in active #AS with an inadequate resp to prior biologic – pivotal phase 2/3 RCT of 420 AS pts (Dz dur 7.7 yrs; 83% B27+) showed better ASAS40 at wk 14 w/ UPA vs PBO (45% vs 18%; P<0.0001) #EULAR2022 POS0306

  9. 10% of PsA is PsA Sine Psoriasis – how to differentiate from seroneg RA? PsA sine PsO pts have peripheral arthritis, no skin dz, but may have axial sxs, +Family Hx or nail psoriasis, dactylitis, enthesitis, DIP involvement.

  10. CDC: Immunocompromised account for 12.2% of all COVID-19 hospitalizations, with an increased risk of ICU (aOR=1.26) and death (aOR = 1.34), even if vaccinated (aOR 1.40; aOR = 1.87). In immunocompromised, death rate was not affected by vaccination.

  11. Worldwide metanalysis of FUO shows most common infections to be Mycobacterium tuberculosis (34%), brucellosis (10%), endocarditis (7.5%), abscesses (7%), herpesvirus (CMV,EBV 7%), pneumonia (6%), URI (6%), enteric fever (5%)

  12. FDG-PET/CTscans were used in 58 for FUO evaluations. Dx was Rheumatic (44.5%), malignancy (34.5%), or infectious (10.3%). Most prevalent Rheum dx was vasculitis (17%), especially LG vessel vasculitis. FDG PET/CT is a useful FUO pts

  13. About 1 in 7 systemic JIA are “refractory” to standard Rx. Could the definition be active systemic or arthritic disease, despite IL-1 or IL-6 inhibitors? It could also include pts developing MAS, ILD or amyloidosis. Still, there are many Rx options.

  14. Guidelines for MAS complicating Systemic JIA: Dx is based on: – Fever in sJIA with ^ ferritin > 684, plus – Any 2 of these: elevated PLTs, AST, Triglycerides or low Fibrinogen

  15. Single center comparison of MAS (n 18) to malignancy related mHLH (n = 16). Notable differences seen in platelet (lower in mHLH 29k v 50K), soluble IL-2R (6814 vs 27972), but more hepatomegaly (25% v 0). Less mortality with MAS (22 v 44%, p 0.18)

  16. Cyclic GMP–AMP synthase (cGAS) engages stimulator of interferon genes (STING) to trigger inflammatory cytokines & type I interferons. cGAS–STING activation by genomic or mitochondrial self DNA implicated in autoinflammatory & autoimmune dz  mitochondrial DNA can drive SLE by PMN uptake, NETs, activation of STING & type-I IFN. Maybe same for Autoinflammatory responses were oxidized mtDNA provokes cGAS-STING, binding cytosolic NLRP3, triggering inflammasome activity.

  17. IL-18, Iike IL-1, is a produced by activation of the inflammasome. IL-18 is a potential bioimarker for #AOSD, closely linked to Dz activity & could be a Tx target, either as IL-18 binding protein (Tadekinig alfa) or mAb against IL-18 (phase 1b)

  18. MRP8/14 as a Biomarker in Systemic Juvenile Idiopathic Arthritis 


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