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Depo-medrol Injections for the treatment of PMR

In early July, 2016, while vacationing in the Adirondacks of New York, I began to suffer from significant night pains in my shoulders and hips that completely resolved during the day. When the night pain became widespread, and began to continue during the day, I called my primary care physician and made an appointment to see him on August 2. I then began to search the literature for the cause of my problem.

Based on symptoms, I learned that I was likely suffering from PMR and the treatment would include long term-high dose steroids; which I knew were associated with a significantly increased incidence of bone loss and fractures. Concerned that this treatment might further compromise a colossal spinal injury I suffered in 1995, I searched for treatments that would reduce the cumulative total steroid use

As a consequence of my search, I located a 12 month pilot study and a 96 week controlled trial (Dasgupta, 1991,1998) that compared 120mg injections of depo-methylprednisolone (depo-medrol), every three weeks, with oral prednisolone for the treatment of PMR.

Subsequently, my physician diagnosed my disease as PMR and agreed to try the treatment outlined in the trial. Regrettably, I flared on the seventh and fourteenth days, and was almost crippled with pain by the end of the third week. As a consequence, my wife and I graphed the release profile of depo-medrol and used my previous flare points as a guideline to determine that 80mg weekly injections should be the minimum dose necessary to control my symptoms.

We also determined the daily doses (from day one to seven) would be approximately: 20mg, 15.3mg, 13.7mg, 10.3mg, 8.4mg, 6.4mg, and 5.9mg. Moreover, I would have to wait for the residual from the first two injections (that was released into the blood after the seventh day) to combine with the third injection, before I received the amounts listed above. Once again, my very considerate physician agreed to give this treatment a try.

While this regimen doubled the steroid use outlined in the aforementioned trial, it still averaged just 11.4mg of methylprednisolone per day; which is significantly less than the 20mg oral dose of prednisone my doctor determined was appropriate for my weight.

On the fourth day following the first injection, I experienced a flare that resolved fairly quickly, but by the end of the second week all of my symptoms were controlled. Subsequently, on the occasional week, I experience mild to moderate hand and shoulder pain on the sixth and/or seventh nights, when the drug cycle is at the lowest levels.

Interestingly, I went to bed with hand and shoulder pain on one of these occasions, and thirty minutes later it suddenly resolved. Simultaneously, I experienced what I believe was a cortisol induced euphoria. The implication being, that due to the pulse dynamic of the depo-medrol, the hypothalamus-pituitary-adrenal axis (HPA) had remained intact over the previous ten weeks (just as occurred in the aforementioned trial) and produced more than enough cortisol to offset the inflammation that was causing the pain.

It is now apparent (if the HPA continues to remain intact), that when my physician begins to taper the dose, my adrenal system should readily take over and spare me much of the difficulties experienced by patients who have lost all of their adrenal function.

Has anyone else received a similar treatment? Am I correct in assuming that because this regimen reduces the cumulative total steroid use, and appears to spare the HPA, that it may be a superior alternative to oral prednisone? Unfortunately, receiving weekly injections is inconvenient, (and includes some minor pain discomfort), but the benefits may more than offset these issues.

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Hello Admiral06, greetings from the UK!

Your post makes for fascinating reading and you have obviously done a significant amount of research into this alternative treatment for PMR - thank you.

Although I am not a medic, and with all respect to the immense wisdom and support from other expert contributors here, your experience does suggest that there might be a more efficacious and medically precise treatment for PMR symptoms than the almost universally prescribed oral corticosteroids (typically Prednisolone) which, in themselves, come with a host of nasty side effects - as so many report.

My experience is that, although oral Prednisolone is the drug of choice in the management of PMR symptoms (perhaps due to its low cost?), it really is a massive trade-off in terms of the patient then having to deal with the rather imprecise process of managing both sets of symptoms simultaneously: i.e. balancing the pain, stiffness, fatigue etc presented by either the PMR and / or the steroid reduction at once. From the many accounts I have read from others here, this seems to be a rather arbitrary process even with the 'best' of steroid tapering plans.

From what you say, there is probably far more to solving this medical conundrum than patients simply relying on a commercially 'cheap' and accessible drug to manage PMR symptoms and eventually (via tapering by whatever method) to 'wake-up the sleepy adrenals' (sic) - and your mention of investigations into the functioning (or otherwise) of the HPA axis must be relevant here.

It also seems that, as some here have said, solving the mysteries of effectively treating underlying PMR symptoms is as much (or more than?) one for Endocrinologists as Rheumatologists - let alone GPs / family doctors who often have little knowledge either of the illness itself, nor any reliable treatment regimen for the symptoms.

That said, I realise that the financial constraints that public health services in many countries have just don't allow the luxury of funding more in-depth / specialist analysis for patients with chronic illnesses where there is no life-threatening element.

Either way, I, for one, will be interested to know your progress and look forward to following your posts and others' responses to it.

Best wishes

Mark B.


I know at least one lady in the UK who is managed with depot Medrol injections because she cannot take oral pred. She however does not have weekly injections, they started at about once a month, became more spread out until she had a GCA flare when they were put back to 3-weekly and then she lengthened the interval again. I don't know what stage she is at at present though.

The concept of Depot-Medrol injections is now included in the 2015 Recommendations:

See Recommendation 5

However - while it is possible that a low dose such as 80mg/week may not come with significant side effects if higher doses are needed then the potential for side effects and poor recovery of adrenal function remains. My granddaughter was managed with Medrol injections for her asthma because the consultant did not believe she was compliant with medication (she was, her nurse mother worked on the chest ward). Her side effects on the injections were far worse than will oral pred - particularly the mood swings immediately after the shots was administered.

There are very many patients who have few problems with oral pred, getting to the lowest dose that manages the symptoms without flares is a significant point in management and done carefully that is not that difficult with oral pred. You do not stay at 20mg - that is rarely necessary and probably a sign this may not be PMR, and most patients will be down to 10mg within a few months if they go about it sensibly. However, I have come across US patients who have been told to remain at 20mg for a year - that really is totally OTT for PMR. Originally I started on 15mg and reduced to 10mg after 2 weeks - I was fine. Unfortunately the rheumatologist used the pred poorly and stopped it after 6 weeks and I had a major flare - it took a long time to get down to 10mg the next time but 10mg was more than comfortable.

Forgive a tad of scepticism but I'm sure weekly injections are very attractive within some medical systems. If I couldn't administer my own I wouldn't be enthusiastic to be honest - a weekly appointment with a doctor is a pain in the anatomy! I know that from personal experience. And a weekly injection isn't something many patients would be too keen on - many would never manage to administer it without a trip to the GP. I know it does require access to a nice large bit of muscle - so shots in the rear are not an option if you want to DIY!


Thanks for your 2 cents. That was looking very attractive.


I think it is quite attractive - but not on weekly injections. I'm not entirely convinced it is BETTER - I think it is an alternative.


I managed PMR on injections because I couldn't take the tablet form of Pred. OK, I wasn't always completely pain-free (but what I had was generally manageable), but the lack of some of the side effects of the tablets - moon face, weight gain, disturbed sleep, mood swings - made it less awful to deal with the condition. Jabs didn't lessen the bone loss though.

I started on fortnightly jabs of 120 mg and then over time stretched out the jabs - but then my Rheumy observed that I was better on smaller, but more frequent doses and reduced the dose (can't now remember the titration rate, but can look it up if you're interested) and kept to jabs about every three weeks. Eventually, due to the bone loss issues, I was put on Methotrexate as well, which did help me to get off the steriod more quickly, but have to say didn't do much for the pain management unless I was prepared to keep going and 'punch' through the pain to find I actually had more movement there.

Overall I would say I probably had slightly less steriod than I would have had, as the jabs seemed to be good at maintaining a more constant drip-feed of the drug to my body so I didn't have to go up and down on numbers of tablets to keep control - and I didn't flare and thus reduced the dose well - and then the 'Meths' helped me over the last months. All in all I had drugs for just under two years and have had no relapses and am utterly delighted to say I'm free of the wretched condition. Hope you will be too, in the not too distant future!


You can't really equate injections to no side effects on the basis of a study of one.

I have been on 3 oral forms of steroid. With one I had next to no side effects, with Medrol in oral form it was awful - weight gain and moon face, beard - and with the third I have lost all the weight and am perfectly back to normal. I have had no bone density problems on any of the oral forms . About 25% of patients with PMR get off steroids in about 2 years anyway whether they take mtx or not. With the third version I reduced with no flares - the flare I had has been while on a stable dose. Whatever you take an increase in autoimmune disorder activity is possible. I haven't had to "go up and down on numbers of tablets to keep control" nor have many others.

It is horses for courses - and everyone is different. It really isn't possible to say that because someone else did well, you will too. It is an alternative.


Hi PMRpro. thanks for the reply. While I found three studies (one PMR, one MS, and one kidney transplant) that favorably compared depo-medrol to oral prednisone, I am merely trying to equate cumulative total steroid use to side effects; which has been well documented.

It is interesting to note, however, that the goal of steroid pulsing (whether it be oral, intramuscular, or iv) is to achieve rapid immunosuppression and antimlammatory effect, while reducing toxicity. Interestingly, depo medrol is commonly used in steroid pulse therapies.

With reference to different forms of steroids, prednisone is converted to prednisolone by the liver, but side effects may result from the metabolic process. Methylprednisolone is nothing more than prednisolone with a metyl side chain added that increases the activity of the drug by approximately 20%. Injectable drugs do not have to go through the digestive system, which may be an advantage, but as you say, each can produce its own side effects.

I have a friend who is a pharmacist and a specialist in pharmaceutical quality control who calls steroids the "Devils's Drugs"

PS I read and enjoyed your posts before I joined the group and you are the main reason I joined.

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He may call it the Devil's drug - but I'll bet he has never had a condition where it is the only way to achieve a reasonable quality of life. Until they find something better - I'll sell my soul to the devil...

Yes, there are long term cumulative side effects - but the ones that seem to cause most problems for patients are the ongoing variety. Pulse therapy does have its advantages, not arguing about that, but it also can have downsides in PMR where allowing even minor flares to occur on a repeated basis by yoyoing the dose seems to make the long term reduction more difficult. In some people PMR dies out in 2 or 3 years, in others it takes longer, and it is impossible to say in advance whether you will be a 2-year person or a 6-year person. This makes it very difficult to say then whether a given regimen encourages an early remission - I have my doubts there is anything much that would "encourage" an early remission. It will take its time and go when it wants.

Thank you


PMRpro, Thanks for your reply. My plan is to ask my physician to run an ACTH blood test before the final tapering occurs; to see if my adrenal system has been preserved. If it has, I hope problems associated with tapering should be minimal. If not, the following chart I created demonstrates how depo-medrol performs during tapering. Please remember that oral pred peaks two hours after ingestion and then falls to near zero over the following 24 hours. This presents the HPA with a continuously changing level every minute of the day. Also remember the pulse dynamic of this drug was designed by Upjohn to preserve adrenal function if a single dose is administered.

Each value on the following chart, is the approximate level which will remain nearly constant over a 24 hour period as the bolus in the gluteal muscle releases methylprednisolone directly into the blood stream at a constant but diminishing rate. I could be wrong, but I believe these gradual steps should be easier for the HPA to track than a moving target that drops from peak levels to zero over each 24 hour period.

I attempted to find research on tapering with depo-medrol, following long term use, but could not find anything. All I have is the Dasgupta document that showed adrenal function was preserved in 30 participants who received depo medrol injections in his 96 week trial.

I also attempted to copy and paste a complete chart from 80mg down to 10mg over a three week period, but it would not fit on this page.

DAY 40mg 30mg 20mg 10mg

1 10.2 7.6 5.1 2.6

2 7.8 5.9 3.9 2.0

3 7.0 5.3 3.5 1.8

4 5.2 3.9 2.6 1.3

5 4.2 3.2 2.1 1.1

6 3.2 2.4 1.6 0.8

7 3.0 2.2 1.5 0.7


PMRpro, On second review, the oral pred may provide a moving target for the HPA, but the daily average dose remains constant. For example, a 5mg tablet provides an average of approximately 2.5 mg per day which continues to repeat every day; whereas the amount from the depo-medrol continues to change. GOT IT! Unfortunately, the best alternative would be a long acting drug that produces a constant serum level for multiple days. I believe an example of this is depo-prevera. There are also 24 hour antihistamines.


I honestly don't think it makes a significant difference overall - a pilot of 30 patients is VERY small and I'd bet you could choose 30 patients on oral pred who all had no problems reducing to zero in terms of adrenal function - the vast majority do as long as they go slowly enough. There are many patients who have few pred problems too.

Obviously Dasgupta's evidence wasn't felt to be particularly powerful or the most recent recommendations might have been rather more in favour of using depot medrol injections:

"The reasons why the panel did not endorse a

strong recommendation for the use of i.m. methylprednisolone are the following:

1) the efficacy of i.m. methylprednisolone is supported by a single randomized controlled trial and confirmation of these data is still necessary (23,36);

2) this trial was neither designed nor powered as a non-inferiority trial and therefore, a difference between the efficacy of i.m. and oral GC cannot be excluded;

3) the trial failed to demonstrate a reduction in GC-related adverse events except for weight gain;

4) the long-term benefit of this preparation is unknown (particularly with respect to a possible reduction in GC side effects); and

5) i.m. methylprednisolone is not available in all countries."

He was part of the committee after all!


Hello Green_girl, and thanks for the comprehensive reply. I'm sorry to hear about your problem with osteoporosis as this is one of my greatest concerns.

For this reason, I did some comprehensive research on calcium supplementation so I could maintain healthy bones, muscles, and nerves during and after this hellacious treatment. I hope the following will help you and others on HealthUnlocked:

With respect to calcium supplements, the four most commonly available sources are listed below. As you can see, the percentage of each that can be assimilated by the digestive system and incorporated into the bone is highly variable. Moreover, while insufficient calcium intake is a serious problem, recent research indicates an overload of calcium caused by drinking too much milk, along with taking calcium supplements or antacids, can cause a host of serious side effects. These include: hypercalcemia, (a shift in the body's acid/base balance towards alkaline), calcinosis and nephrocalcinosis, (calcium deposits in the tissues and kidneys), kidney stones, plaque in the arteries, and an increased risk of heart attack, stroke, and kidney disease.

• Calcium carbonate (40 percent elemental calcium)

• Calcium citrate (21 percent elemental calcium)

• Calcium gluconate (9 percent elemental calcium)

• Calcium lactate (13 percent elemental calcium)

The recommended daily allowance (RDA) of calcium for an adult, published by the Food and Nutrition Board (FNB) at the Institute of Medicine of the National Academies, is 1000–1200 mg and based on the latest research, it seems best to get as much calcium as possible from natural food sources while minimizing supplemental calcium; especially calcium carbonate. Interestingly, the number the RDA is based on, (the number that really matters), is how much calcium you absorb, not how much you eat. The average adult needs 300-400mg of calcium that can be readily metabolized and used to satisfy the body’s calcium requirements.

The following is a very short list of the high calcium food items that have been tested for bioavailability. I chose to leave out the minor sources, as well as fortified foods (such as calcium fortified orange juice, calcium set tofu, calcium fortified soy beverage, etc.), as they include nothing more than supplemental calcium added to each of these food items.

Food Serving Size Calcium absorbed per serving

Collard greens 1 cup cooked 173mg

Canned salmon (6 oz with bones) 1 6-ounce serving 114mg

Turnip greens 1 cup cooked 102mg

Milk, Lactaid, yogurt 1 cup 96mg

Cheese (hard such as cheddar) 1 ½ oz 97mg

Sardines (with bones) 1 can (3.75oz) 95mg

Bok choi 1 cup cooked 69mg

Broccoli 1 cup cooked 57mg

Kale 1 cup cooked 46mg

Mineral water 20oz bottle 41mg

Mustard greens 1 cup cooked 42mg

Chinese spinach ½ cup 29mg

Almonds 1/4 cup 22mg

Beans (white) 4 oz 25mg

Beans (pinto) 4 oz 15mg

Beans (red) 4 oz 10mg

Whole wheat bread 1 slice 17mg

A glance at this list makes it immediately apparent that without milk and milk products it is very difficult to meet the daily requirement for bioavailable calcium without relying heavily on supplements. This, however, is complicated by the fact that approximately 25% of Americans are lactose intolerant. Fortunately, Lactaid can be substituted for milk, and many lactose intolerant people, myself included, can eat small portions of hard cheeses without a problem. The reason for this is much of the lactose in cheese is converted to lactic acid when the milk and cream are cultured, and more drains off with the whey during the aging process.

Additional little known facts are that green leafy vegetables, which are very rich in calcium, often contain phytates and/or oxylates. These “antinutrients” bind to the calcium in the cells of each plant and block its bioavailability. A good example is spinach, which contains 115mg of calcium per ½ cup, but only provides 6mg that can be metabolized and used to meet the body’s calcium requirements. Furthermore, when these foods are included with a meal, the phytates and oxylates they contain bind with the calcium in other food items you eat and block its absorption as well. So much for “Johnny eat your spinach”, and Popeye the sailor man.

Vegetables high in oxylates include: carrots, spinach, okra, kale, chard, beet greens, rhubarb, collard greens, broccoli rabe, turnip greens, and Brussels sprouts. From the above chart, however, it is obvious that collard greens and turnip greens are so high in calcium that the negative impact of the oxylates on other food items may be more than offset by their high bioavailable calcium content.

Foods high in phytates include: whole grains, nuts, seeds, beans, and legumes; with beans being the biggest concern. Fortunately, the phytates in whole wheat bread are removed during leavening, so this staple remains both a healthy food and a good source of calcium.

Lastly, it has been shown that vitamin D3, magnesium, and vitamin K2 work either synergistically with calcium, or contribute to its absorption.

Based on the aforementioned research, my daily calcium intake now includes what I believe to be a nutritious diet, plus the following supplementation:

1 cup of Lactaid 96mg

2 ounces of low fat hard cheese 129mg

1 can of sardines, 1 serving salmon, or a third dairy 95mg

600mg of calcium citrate (21% elemental calcium) 126mg

Total 446mg

Because this regimen satisfies my daily calcium requirement, we can continue to enjoy antinutrient containing green vegetables with our dinners and benefit from the fiber, vitamins, minerals, and disease fighting phytochemicals they contain.

Lastly, I take 2000mg vitamin D3, 200 mcg vitamin K2, and 500mg Magnesium to augment calcium absorption.

I hope everyone finds this helpful………and please stay well as you deal with this formidable disease.

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Let's cheer people up regarding kale, shall we?


But don't overdo the kale if you are on warfarin or similar...

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Ah yes, the Vitamin K1....


Hi Green_girl, I attempted to post a reply, in this box, but it showed farther down the page. Thanks for the information, this is helpful to me.


Your description of some of the effects of these injections is alarming to say the least. It will be interesting to hear more from you as your journey progresses. I think all of us would like to preserve our body's ability to produce its own chemicals efficiently, but I don't know why your adrenals would not be as affected by the injections as ours are by the pills. Is there some research on this?

PMR is not treated with long term high dose steroids. Long term, yes, (anything over three months is long term) but most of us do get to what is a low dose within a few months of starting with a moderate dose. The high dose is reserved for GCA in order to preserve sight. If moderate pred does not control pain quite quickly (within a few days) it may well be because it isn't PMR in the first place or, as is quite common, there are other issues going on. My case: prednisone at 15 mg in June 2015, tapered down to physiological level of 7 mg by January 2016, have been at 3 for about three months now (October). This is a little faster than some can manage, but I've tapered slowly and done everything I can think of to improve my health generally, including supplements and exercise (no meds) for the bones. At no point in this entire journey did I experience any of the ups and downs you describe from the injections. A few hiccups, yes, where I had to slow the taper and in the case of the most recent attempt reverse it, but nothing dramatic.

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HeronNS, The ups and downs I described, occurred while I was trying to find a maintenance dose; using a non-traditional therapy. There was nothing alarming about it. Also please divide 80mg weekly by seven, and you will find I am on a beginning regimen that averages just 11.4mg per day; which is not very high for someone who weighs 215 pounds. My physician wants me to stay at this level for 12 weeks, then we will find the second minimum maintenance dose. Re: Preserving adrenal function, look at the references I gave in my post and you will find that all participants successfully preserved their HPA because of the steroid pulse characteristics of depo-medrol. Furthermore go back and look at the daily numbers I calculated. The dose on the day of the injection is 20mg, and by the 7th day it is down to 5.9mg; which is below the level that the HPA normally maintains. This is what I refer to as a pulse, and this is how this drug attempts to preserve adrenal function.

Additionally, on this regimen, my sed rate dropped 46% and my CRP came down 82.6% in just four weeks. I suspect this is because Depo-medrol is released directly into the blood stream from a "bolus" in the gluteal muscle (bum on your side of the pond), at a constant but diminishing rate over 18 days, and the serum levels I quoted in my post are maintained for 24 hrs. In contrast, a 20 mg dose of oral pred reaches its peak 2 hrs. after it is ingested, than tapers to almost zero over a 24 hour period. This results is an average serum level of approximately 10 mg.

Please think of the anti-inflammatory effect of constant 24 hr. serum levels vs. a drug with a shorter half life that begins high, but falls to near zero each day. Please also consider that for four days each week, 80 mg of depo-medrol maintains serum levels that are higher (for a full 24 hours) than the average serum levels from a 20mg dose of oral pred; which is a 1.5 times larger. When the drug tapers, however, the levels are lower for the last three day, but a large anti-inflammatory event has just taken place, and the tapering is designed to preserve adrenal function. Nothing is perfect, and there are trade-offs that one must intellectualize. The final outcome of the regimen I am on in unknown, but so far I think it may be a winner.

I wish I were on your side of the pond, so we could sit over a brew, while we discuss my extensive research, and what I learned from a retired pharmacologist who once worked for Pfizer. (Pfizer is the manufacturer of depo-medrol)


You *are* on my side of the Pond - I'm in Canada! Sorry, I was just reading down the posts and when my questions occurred I didn't think to look back. However when I did go back just now I remembered I'd promptly dismissed the idea when I saw the dates of the study, the 1990s. Surely if it were that great, I think as I read on, we'd all be on some form of this treatment and not on our little pills.... it is an adventure isn't it? Of course when we start the pills they give us enough to knock the inflammation out and then it's up to us to wean down to a maintenance dose. I'm curious about the evidence that a constant dose of the medication via injection preserves the HPA axis as I'd heard the opposite - that having many hours without the medication in the bloodstream is a good thing! So I will follow your journey with great interest. Cheers!

BTW I think this is the article you referred to?



HeronNS, If you read "2015 Recommendations for the Management of Polymyagia Rheumatica" you will see the depo-medro therapy outlined in the 1998 trials remains a recommended treatment under certain conditions. Additionally, Dasgupta, who conducted the 1998 trial, wrote a paper two years back that recommended this therapy when bone loss is a significant concern. .

If you go back to the beginning of my post, you also will see that I suffered a colossal spinal injury in 1995; which I believe made me an appropriate candidate for this conditional recommendation; my physician agreed. Regrettably, 120mg injections every three weeks did not work for me, but I continued to believe that using a steroid pulse therapy to preserve adrenal function and minimize steroid induced side effects made a lot of sense. For this reason, I asked my physician to consider 80mg weekly injections as a second alternative.

You also said you were curious about the evidence that a constant dose of medication via injection preserves the HPA axis as you had heard the opposite. You must have missed the part (at least 3 times) about this being a steroid pulse, therapy; not a constant dose. Once again, I recommend you read the 1998 trials. They may be old, but Dasgupta remains a world renowned rheumatologist, who was part of the international committee that published the 2015 recommendations.

In answer to your comment that if it were that great we'd all be on some form of this treatment; I think the reason may be based on comfort, convenience, cost, or simply because a trial has never been conducted to determine it merits. markbenjamin57 seems to have an excellent grasp of this, and I recommend you read his post above.

Additionally, I did not advocate the regimen I am on when I posted. I listed what I thought were its advantages, and asked if anyone knew if it had been used before. I am, however, a retired bio-medical engineer and have downloaded and studied virtually every word that has been written about this formidable disease. And I did not reject any information because of its age, but rather used what I believed to be logical and correct as a tool to increase my knowledge.

Lastly, I am both educated and informed, but do not consider myself an expert by any measure. I am here to learn what I can, and be corrected by others (who are also educated and informed) if any of my logic, facts, or conclusions are incorrect. I am neither reckless, nor is this an "Adventure" as you insinuated. I spoke with doctors, pharmacologists and a former Pfizer employee before I decided to try these treatment options, and my motivation was to minimize systemic inflammation, with the lowest possible steroid use.

Incidentally, my Sed Rate dropped 48% and my C-Reactive protein dropped 82.6% just four weeks after this "Adventure" began. While I don't have enough experience to know if this is a good result, but my physician informs me that it is excellent!


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