4 ms·

Regarding the rejection, ask about low-dose methotrexate! It helps prevent your body from building up a resistance against those sweet, sweet monoclonal antibod

Regarding the rejection, ask about low-dose methotrexate! It helps prevent your body from building up a resistance against those sweet, sweet monoclonal antibodies. I was hesitant at first thanks to how many MTX horror stories I've heard, but those dose is so small that I thankfully haven't experienced any side effects. Just 7.5mg once a week.

atombender 3y ago
The evidence here is actually very slim. There are some studies that show a mildly positive effect on drug survival, but of these, the longest studies have typically been only a year or less. A recent Dutch single-blind RCT (van der Kraaij et al. 2023 [1]) on adalilumab on psoriasis with/without methotrexate reported very favorable results after one year. However, when they their third-year update basically concluded that the effect was not real. As a counterpoint, many of their patients exited the study by the end of the third year (sometimes due to adverse events), and so at the end they had just 8 patients left in total. They use some statistical techniques to account for this, but I'm not a statistician and don't know if they make sense. Some commentary here [2]. As an aside, it's interesting that most studies typically look at ADA (anti-drug antibody) serum levels and not actually at clinical efficacy. A few studies do look at both. I'm inclined to think that it's better to be safe than sorry, but that's in spite of the evidence. Regarding MTX horror stories, there are some things one can do to prevent/alleviate side effects [3]. One thing that's not known by most doctors is that a lot of people (maybe as many as 40% of the U.S. population) have a genetic mutation that impacts the body's ability to activate folate. The MTHFR 667CT genotype reduces folate activity by about 35-40%, while having two copies of the mutation (677TT) reduces it by about 70-80%. Since MTX is a folate antagonist and folic acid is taken to counteract this, it means that for many people, the folic acid doesn't do its job. There are two alternatives (folinic acid and L-methylfolate), both widely available by prescription, that don't have this problem, and some rheumatologists swear by them. A formulation called Rheumate (L-methylfolate plus curcumin) was developed specifically for use with methotrexate. [1] https://pubmed.ncbi.nlm.nih.gov/37014287/ https://pubmed.ncbi.nlm.nih.gov/37014287/ [2] https://onlinelibrary.wiley.com/doi/10.1111/jdv.19282 https://onlinelibrary.wiley.com/doi/10.1111/jdv.19282 [3] https://rheumnow.com/content/dsb-managing-methotrexate-toxicity https://rheumnow.com/content/dsb-managing-methotrexate-toxic...
- spondylosaurus 3y ago
  Oh, interesting; thanks for the links! One thing you might find notable is that my gastro wasn't the one who put me on MTX, even though he's the one who put me on infliximab—a rheumatologist suggested it. Although that rheumatologist didn't have me on MTX when I'd previously been taking adalimumab under his care. Not sure why he suggested it for one TNFi and not the other! And yeah, I'm also inclined to think "better safe than sorry" here, especially with how cheap generic MTX is :P Re. the folic activity: this does seem like it could explain a lotttt of negative experiences I've heard! It doesn't seem like I'm one of the 40%, but my dose just might be too low to tell. If I ever need to up my dose, I'll definitely ask my rheumatologist about Rheumate :)

atombender 3y ago

The evidence here is actually very slim. There are some studies that show a mildly positive effect on drug survival, but of these, the longest studies have typically been only a year or less. A recent Dutch single-blind RCT (van der Kraaij et al. 2023 [1]) on adalilumab on psoriasis with/without methotrexate reported very favorable results after one year. However, when they their third-year update basically concluded that the effect was not real. As a counterpoint, many of their patients exited the study by the end of the third year (sometimes due to adverse events), and so at the end they had just 8 patients left in total. They use some statistical techniques to account for this, but I'm not a statistician and don't know if they make sense. Some commentary here [2]. As an aside, it's interesting that most studies typically look at ADA (anti-drug antibody) serum levels and not actually at clinical efficacy. A few studies do look at both. I'm inclined to think that it's better to be safe than sorry, but that's in spite of the evidence. Regarding MTX horror stories, there are some things one can do to prevent/alleviate side effects [3]. One thing that's not known by most doctors is that a lot of people (maybe as many as 40% of the U.S. population) have a genetic mutation that impacts the body's ability to activate folate. The MTHFR 667CT genotype reduces folate activity by about 35-40%, while having two copies of the mutation (677TT) reduces it by about 70-80%. Since MTX is a folate antagonist and folic acid is taken to counteract this, it means that for many people, the folic acid doesn't do its job. There are two alternatives (folinic acid and L-methylfolate), both widely available by prescription, that don't have this problem, and some rheumatologists swear by them. A formulation called Rheumate (L-methylfolate plus curcumin) was developed specifically for use with methotrexate. [1] https://pubmed.ncbi.nlm.nih.gov/37014287/ https://pubmed.ncbi.nlm.nih.gov/37014287/ [2] https://onlinelibrary.wiley.com/doi/10.1111/jdv.19282 https://onlinelibrary.wiley.com/doi/10.1111/jdv.19282 [3] https://rheumnow.com/content/dsb-managing-methotrexate-toxicity https://rheumnow.com/content/dsb-managing-methotrexate-toxic...

spondylosaurus 3y ago
Oh, interesting; thanks for the links! One thing you might find notable is that my gastro wasn't the one who put me on MTX, even though he's the one who put me on infliximab—a rheumatologist suggested it. Although that rheumatologist didn't have me on MTX when I'd previously been taking adalimumab under his care. Not sure why he suggested it for one TNFi and not the other! And yeah, I'm also inclined to think "better safe than sorry" here, especially with how cheap generic MTX is :P Re. the folic activity: this does seem like it could explain a lotttt of negative experiences I've heard! It doesn't seem like I'm one of the 40%, but my dose just might be too low to tell. If I ever need to up my dose, I'll definitely ask my rheumatologist about Rheumate :)