Anybody use NSAIDS, in particular cox-2 inhibitors?

[TLJ-1]

Use of NSAIDS is strongly discouraged for those of us using an anticoagulant due to the small risk of gastrointestinal bleeding that NSAIDS pose. Using an anticoagulant poses its own risk of GI bleeding, but we still use the anticoagulant since we regard the risk as lower than the risk of blood clot formation if we don’t use the anticoagulant. However, in reading papers reporting large scale studies (some meta-analyses) of NSAID risk, it appears that at least the cox-2 inhibitors (e.g., Celebrex) pose no higher risk than the common anticoagulants. Sure, doubling the risk of GI bleed doesn’t seem like a good idea by taking both, but I wonder if the benefits of reduction in pain and fatigue caused by the cytokines we experience in myelofibrosis (personal experience), ET or PV might weigh against that risk. So, finally, my question: have any of you been taking an NSAID and unequivocally experienced a reduction in fatigue and/or pain while you are being treated for an MPN? I expect pain reduction, but I really wish to know if there is a potential benefit in fatigue reduction.

[hunter5582]

I have only ever used aspirin as an antiplatelet medication. While on aspirin, I have been on high dose ibuprofen, Meloxicam, and Lyrica to control the pain associated with osteoarthritis. None of these meds worked for me and the NSAIDs did exacerbate the bleeding tendency that aspirin causes.

I am very fortunate that my rheumatologist suggested that I try a curcumin supplement, Curcumin works better for me than any NSAID I ever used. It makes a huge difference in my pain and level of function from the osteoarthritis. While there are warnings about curcumin potentiating the blood thinning effect of aspirin, I have not seen any difference.

I now consult with an Integrative Medicine doctor about the use of complementary health approaches. She confirms that systemic inflammation is a real and very important issue to mange for those of us with MPNs. She also recommends curcumin. In addition, she added L-Glutathione (related to N-Acetylcysteine) and SPM Active (a proresolving mediator) to help control systemic inflammation. These supplements have not caused any excess bleeding for me with the aspirin. My MPN Specialist and hematologist are aware of my use of these supplements in addition to aspirin. They do not have a problem with it. Note that I always let my entire care team know about everything I take.

I believe that most anything that is anti-inflammatory also tends to be blood thinning and will potentiate an anticoagulant to some degree. Some agents more than others. I can only speak from my own experience which is that curcumin works better and has less bleeding risk than NSAIDs.

We always have to weigh the risk/benefit profile of anything we choose to take. I do not know if there would be any benefit in terms of fatigue, but I know for certain about the pain reduction. Reducing pain and staying functional is worth some degree of risk. These risks should be calculated with expert consultation. Most doctors are not familiar with many complementary health interventions. That is why consultation with an Integrative or Functional Medicine doctor is so important if you want to consider anything like this.

All the best moving forward.

[TLJ-1 in reply to hunter5582]

I really appreciate you sharing your experience. It appears that you have found something that helps you with your pain – that is wonderful. It is interesting that you have found curcumin to be useful. It must behave radically differently in individuals. I had seen that some people were using it, but then I found a 2017 review in a journal I know to be reputable that cited 120 clinical studies that found no medical utility for curcumin [J. Med. Chem. 60, 1620–1637 (2017)]. The table reported in RM Scherber et al, Blood 131 (Suppl. 1), 2193-5, (2017), which doesn't list curcumin, does list N-acetylcysteine as the only supplement to reduce MPN symptoms. Of course, that supports your use of glutathione. I started using NAC but found no improvement after taking 600 mg/day for 10 weeks. A week ago, I increased that to 600 mg twice/day. Since I've already had my 24 hr in the ICU with numerous small pulmonary thrombi, I was put on Xarelto (rivaroxaban). What I really want to discover is something that will help with the knock-down fatigue that occurs in the middle of the day. The pain is not good (I have ankylosing spondylitis already), but fatigue is ruining my life.

[hunter5582 in reply to TLJ-1]

The fatigue issue is difficult. I am fortunate that I only experienced mild fatigue when I was too iron deficient from the phlebotomies. Some people have reported an improvement in fatigue with the meds used to treat MPNs, but others find the fatigue worse due to the same meds. I expect you have already seen the lifestyle change interventions listed on the MPN Voice and other sites. About the only thing I could suggest would be a thorough nutritional analysis. Various nutritional deficiencies can contribute signifcantly to fatigue.

mympnteam.com/resources/man...

patientpower.info/myeloprol...

mpnvoice.org.uk/living-with...

Angela Fleishmann address the issue of research into supplements in one of her recent presentation. The core issue is that there simply is not sufficient funding to pay for the research needed to validate the use of supplements like curcumin. In short, Big Pharma is not going to fund research where they cannot make any money.

The core issue is that curcumin is not readily bioavailable. It needs help to enter the bloodstream. Some formulations are much better than others. Some are essentially worthless. Some help, but with specific type of inflammation. Here is one example of that type of data.

ncbi.nlm.nih.gov/pmc/articl...

There is the one study on curcumin and MPNs that is of interest.

ncbi.nlm.nih.gov/pmc/articl....

The truth is that I did not research curcumin thoroughly when I decided to try it. The rheumatologist suggsted I try it since Lyrica and the NSAIDs were not working for me. I am fortunate that the first formulation I tried was bioavailable and worked for me. Coincidentally, it is the same formulation my Integrative Medicine doc recommends. While I have since seen some supporting research, the truth is that it is my personal (and subjective) experience with it that guides my continued use.

All the best to you and I hope you find a solution for the fatigue.

[TLJ-1 in reply to hunter5582]

Thanks very much for your thorough (and helpful) response, Hunter. I'll check out some of those links you provided. Just maybe the right curcumin might be found for me too.

[PhysAssist]

Hi TLJ-1,

I have at least a few areas where [osteo] arthritis cause me a lot of trouble- e.g., I have already had 1 knee replaced, and the other appears to be moving along that path as well.

I have been taking Nabumetone for my arthritis symptoms for several decades now, as it is the only NSAID that doesn't also cause my GERD [heartburn] to flare up- including the COX-2 selective NSAIDs that are not supposed to do so.

I had to stop taking it for about a week prior to my knee replacement in 2010 [at which time, in retrospect, my HCT and Hgb were already elevated, although not enough to be used as a diagnostic for an MPN], and I was miserable the whole time- achy, fatigued, brain-fogged, etc.

All of those symptoms resolved within a week or so of re-starting Nabumetone.

Nabumetone is a unique medication, because it is what is termed a "pro-drug", meaning that it is completely biologically inactive [and specifically is non-acidic] when taken internally- to reiterate it has literally NO effect on the tissues it comes in contact with in its original form [whether it is in solid form or dissolved in stomach acid, etc.].

However, when it passes into the liver from the portal vein [which runs from the digestive tract to the liver and is responsible for transport of everything ingested [and digested] getting to the liver for processing], the liver transforms it into an active anti-inflammatory agent- which has some, but not complete COX2 selectivity.

Gastrointestinal safety profile of nabumetone: a meta-analysis

Abstract

Individual comparative studies suggest that nabumetone has a gastrointestinal (GI) safety profile superior to comparator NSAIDs but lack power to show a statistical difference. The aim of this study was to evaluate systematically the difference in GI adverse events--especially the rate of perforations, ulcers, and bleeds (PUBs)-- between studies, meta-analyses of comparative trials of nabumetone and conventional NSAIDs, and post-marketing, open-label studies of nabumetone meeting predefined inclusion and exclusion criteria. A fully recursive literature search identified 13 studies consisting of 29 treatment arms and 49,501 patients that met the predefined criteria. Tests for heterogeneity found no significant difference between studies of each subgroup. Overall, the dyspeptic symptoms flatulence, constipation, and diarrhea were the most commonly reported adverse events accounting for 98.6% of the total GI adverse events. Significantly more patients treated with a comparator NSAID experienced GI adverse events than did those taking nabumetone (P = 0.007). After adjustment for patient-exposure years, PUBs were 10 to 36 times more likely to develop in patients treated with a comparator NSAID than with nabumetone. This was consistently seen in patients in nonendoscopic (n = 7,468) and endoscopic studies (n = 244). In the analysis of postmarketing or open-label studies of nabumetone, only one PUB was reported per 500 patient-exposure years over 17,502 treatment years (n = 39,389). GI adverse event-related dropouts and hospitalizations were increased by 1.3- and 3.7-fold if patients were treated with a comparator NSAID than with nabumetone. Significantly fewer treatment-related GI adverse events, especially PUBs, are seen in patients treated with nabumetone than with a comparator NSAID. Nabumetone is very safe for the GI tract.

pubmed.ncbi.nlm.nih.gov/106...

This is important, because when we talk about increased bleeding risk from NSAIDs [and especially with them in combination with anticoagulants] we are primarily referring to GI [stomach or duodenal] bleeding.

Also:

pubmed.ncbi.nlm.nih.gov/106...

pubmed.ncbi.nlm.nih.gov/108...

pubmed.ncbi.nlm.nih.gov/107...

pubmed.ncbi.nlm.nih.gov/184...

pubmed.ncbi.nlm.nih.gov/154...

I hope these are helpful for your thought process. The last article link gives the recommended dosing information as well as supporting its safety.

Best,

PA