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Methotrexate: shall we split up?
Methotrexate is widely used in rheumatic diseases yet poses common tolerance issues, especially for the oral form; and bioavailability is known to be limited for doses over 15mg. In the SMART study, Prasad et al. present the first RCT comparing either single dose (25 mg) or split-dose (10 mg morning, 15 mg evening, same day) once weekly MTX for 24 weeks.
ACR23 – Day 1 Report
ACR 2023 is back in San Diego for its annual convergence of thousands of rheumatologists to partake, discover and learn from thousands of abstracts and hundreds of sessions and presentations. It was a big return for the Poster Hall with rows and rows of research, friends, fellows and poster tours. Below are a few of my favorite presentations from the posters, Plenary and oral sessions on day one.
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Two-week interruption of MTX for IMIDs enhanced boost of antibody responses after COVID-19 vaccination, sustained at 12, 26 weeks. Consistent across ages, MTX doses, route, IMIDs, primary vaccination platform,COVID-19, Abhishek A Abst#1677 #ACR23 @RheumNow https://t.co/T0KdsGh6vg
Dr. Antoni Chan ( View Tweet)
VROOM 🏎️ study
2 wks interruption of MTX just after COVID vaccine:
-Increase S1-RBD Ab response for 26 wks
-Improves Neutralizing Ab titres (Wuhan Hu-1)
-Leads to more flares wks 4 & 12
Greater effect when MTX dose>15mg
@RheumNow #ACR23 ABST1677 https://t.co/SJmaRHtbRH
Aurelie Najm ( View Tweet)
Abishek et al. 2 week break from MTX enhances response to COVID-19 vaccination, mirroring what we saw for flu. Trade off is short term worsening of disease activity. Abstr#1677 #ACR23 @RheumNow https://t.co/gguRWER81x https://t.co/1hncvDTahH
Richard Conway ( View Tweet)
Abst#1583 SMART study: Split dose qwk MTX (10 mg QAM, 15 mg QPM) may have better efficacy compared to 25 mg single dose qwk MTX. RCT 253 RA patients: split dose had better DAS score, less likely to add other DMARDS, but slight⬆️in LFTs. #Plenary #ACR23 @rheumnow #ACRbest
TheDaoIndex KDAO2011 ( View Tweet)
Karpouzas et al. MTX reduces IHD in males but not females with RA. 4362 patients. 66% lower risk MACE and 55% lower risk any ischaemic CVE. Abstr#1627 #ACR23 @RheumNow https://t.co/MC4W0dinUv https://t.co/1hkBoawt4b
Richard Conway ( View Tweet)
RA males 81% increase MACE & 58% ischemic CVE
2 folds Males>Females in MTX non users
Makes MTX users reduction 66% & 55% risk MACE & ischemic CVE and no diff w/ females
MTX use not assoc w/ reduction MACE in females
@RheumNow #ACR23 ABST1627 https://t.co/qbAc2bWdcM
Aurelie Najm ( View Tweet)
SMART study in RA, splitting MTX
Split dosing better at wk 16 but ~similar at wk 24
Caveat: wonky design from wk16-wk24 makes it hard to interpret?
Surprsingly, adverse events ~similar but smallish sample
Mostly supports my practice of splitting?
@RheumNow #ACR23 #ACRBest https://t.co/g7s4EUHeCW
Mike Putman EBRheum ( View Tweet)
SMART study - MTX split into morning and evening once weekly vs all together. 253 patients. Split dosing better efficacy (DAS28 4.1 vs 4.5, p=0.03), more LFT elevation but less neutropenia. Abstr#1583 #ACR23 @RheumNow https://t.co/tkrds4uqQP
Richard Conway ( View Tweet)
Split dose oral MTX (15/10mg) versus single dose (25mg) in RA RCT 250pts
EULAR good resp
16wks 22 vs 10% (sig)
24wks 37 vs 28% (ns)
50% more addition of 2nd csDMARD in single dose
#ACRBest @RheumNow #ACR23
ABST1583
For more thoughts, have a read https://t.co/urA6X4rY0D 👇🏼
Aurelie Najm ( View Tweet)
SMART on MTX
Ab#1583 @RheumNow #ACR23
Single dose MTX 25 mg v Split dose (same day 15/10 mg). FA 5 mg 2x/wk. 16w can add csDMARD
Split 29% vs 22% - EULAR response improve - not signif. Better DAS28
Split: 35% added 2nd csDMARD vs. 54.5% in single dose
No stat diff in sAE
#ACRBest
Eric Dein ( View Tweet)
Should Methotrexate be prescribed as split dosing?
Multi-center, RCT of RA pts showed split dosing of 25mg MTX resulted in higher efficacy + reduced need for additional DMARDs, compared to single dose MTX
@RheumNow #ACR23 Abs#1583 https://t.co/zjjnzWUl5E
Robert B Chao, MD ( View Tweet)
SMART study #ACR23 Plenary abs #1583: po split-dose MTX (vs single dose) once weekly in RA pts had ^^ efficacy & reduced need for add'l DMARDs. No major AE, but slight increase in frequency of persistent transaminitis in split-dose group. https://t.co/wHzjpSnfuA @rheumnow https://t.co/0hNTMGbt47
Dr. Rachel Tate ( View Tweet)
The SMART study by Dhir et al: once-weekly, oral split-dose MTX (10mg/15mg) in RA pts had⬆️efficacy & ⬇️need for addtl DMARDs vs. once-weekly, single-dose MTX
Reassuring.
. . .
In my practice, pts tolerate MTX split dosing better esp w/⬆️doses
#ACR23 ABST1583 @RheumNow https://t.co/F8p2aKmmH4
sheila ( View Tweet)
Does NSAID use = CKD?
Large Korean study on CKD in ankylosing spondylitis pts showed risk of CKD associated with comorbidities.
Long term NSAID use not associated with increased risk of CKD.
@RheumNow #ACR23 Abs#1394 https://t.co/m3kYI30gBc
Robert B Chao, MD ( View Tweet)
Risk of CKD in AS patients was associated with comorbidities, not NSAID use. #ACR23 Abs #1394 https://t.co/cbOPvjOCyq @rheumnow https://t.co/O0rhbMFiOX
Dr. Rachel Tate ( View Tweet)
To remind us. Glory be! GLORIA a #RCT in elderly active #RA: MTX+10 mg daily #prednisolone which was better than MTX alone. But more infections and no comparison of inexpensive Rx such as adding #HCQ. Still debated as to benefit vs risk of this strategy @RheumNow #ACR23 @ACRheum https://t.co/slOmESbIOW
Janet Pope ( View Tweet)
Interesting abstract re:dx trajectories, I have a counter-intuitive take
I expect pts w/high dx activity to respond BETTER than pts w/LDA at diagnosis
More autoimmunity + less fibro = higher chance to respond to DMARD?
Anyone else feel that way?
@RheumNow #ACR23 Abstr1426 https://t.co/D6GU7tMcY6
Mike Putman EBRheum ( View Tweet)
Towards Personalised Care in RA
Since the millennium, we have seen an expansion in the number of advanced treatments both biologic and targeted synthetic disease modifying anti-rheumatic drugs (DMARDs) for rheumatoid arthritis (RA). #ACR23
https://t.co/SjyfMyPyGw https://t.co/uzG72vKSpd
Dr. John Cush RheumNow ( View Tweet)
