Methotrexate treatment - experiences?

[swedishskoda]

I've been diagonesed with Giant Cell Arteritis. Initial treatment is large doses of cortisone which may cause trouble, so my rheumatologist wants to add methotrexate to the cocktail, thus being able to reduce the cortisone dosage.

It seems to be a fairly potent drug, so I wonder about unwanted/unpleasant adverse effects.

Anyone having been treated with low doses of methotrexate for autoimmune diseases, e.g. rheumatic diseases?

[Clunkclick]

I've not had it, but have heard of it in the context of Blood cancer and Lymphoma - medicos shorthand is MTX.  I think they use it to suppress the recipients immune system when they do a stem-cell transplant, which is sort of a last-ditch therapy for Lymphoma.

 

According to my copy of the BMA guide to medicines and drugs (8th Ed, 2011, page 313), its part of the anti-cancer group of meds, has a high risk of overdose, low dependency rating, requires a prescription and is available as a generic.

 

Apparently, it is used for solid cancers such as breast, bladder, head and neck as wells as inflammatory conditions such as severe uncontrolled psoriasis, rheumatoid arthritis and Crohn's disease.

 

Under  the section "How taken/used" , subsection " Adult dosage range" it says Rheumatoid arthritis 7.5 - 20mg weekly, subsection "Onset of effect", 30-60 minutes, subsection " Duration of action" , short-term effects up to 24 hours.

 

Under "Possible adverse effects - common", are Dry cough/chest pain, nausea/vomiting, diahorrea, mouth/gum ulceration/inflammation - that's fairly common to the Lympho Chemo I've just completed.

 

Under "Possible adverse effects - rare", are Mood changes/confusion, rash, jaundice, sore throat/fever, easy bruising/bleeding, breathlessness.

 

**If its anything like the chemo I've just completed the menu of effects is highly specific to each individual and can vary over the course of treatment.**

 

Under "Interactions" it says that NSAIDS, diuretics, ciclosporin, phenytoin, and probenecid may increase blood levels and toxicity of methotrexate.

 

Also, Co-trimoxazole, trimethoprim and certain anti-malarial drugs may enhance the effects of methotrexate.

 

Under "Prolonged use" it says

 

" Long-term treatment may be needed for rheumatoid arthritis.Once the condition is controlled, the drug is reduced as much as possible to the lowest effective dose. Long-term methotrexate treatment may occasionally lead to breathing problems due to scarring of the lungs or, rarely, unusual respiratory infections, such as pneumocystis pneumonia."

 

Under "Monitoring" it says "Full Blood Counts and kidney and liver function tests will be performed before treatment starts and at intervals during treatment".

 

**Sounds like a right little mother**

 

Under  "Special Precautions" it says under "over 60" , increased likelihood of adverse effects. Reduce dose necessary and under "Alcohol" it says avoid - alcohol may increase the adverse effects of methotrexate.

 

** As an aside, in my copy of the Oxford Handbook of Clinical Haematology" (4th edition, 2015, p 424) there's a table for dose reduction applicable to its prophylaxtic use in Graft-versus-host disease arising from a Haematopoietic stem cell transplant i.e. in layman's language a stem-cell transplant from another person. This table identifies certain levels of Creatinine and Bilrubin in the blood as warranting a dose reduction, so that for Creatinine < 145 (Micromol/L) 100% MTX is sustainable, whereas at  > 180 (MM/L) it says the dose should be omitted (There are 50% and 25% dosage levels in between the max and the min dose at the  respective ranges 145-165 (MM/L) and 166-180(MM/L) ).  As for Bilrubin < 35 (Micromol/L)  is Ok for a 100% dose, whereas at  >85 (MM/L) it says omit dose ( Respective ranges for 50% and 25% dose are 36-50(MM/L) and 51-85(MM/L))**

 

Hope this helps.

 

 

My understanding is that most of the these current Chemo therapies are indiscrimatory and relatively unguided i.e. they hit good cells as well as bad and rely on the starting position ratios of good to bad cells to deliver their therapeutic effect over multiple cycles of application. Occasionally, where the therapies employ monoclonal antibodies and the like, such as Ritaximab, used in the R-CHOP therapy that I had, then a modicum of guidance may be utilised  by the immune system in the direction of the chemo "missile". Otherwise its a numbers game (What the medicos call a reductionist therapy rather than elimination) which progressively widens the gap between the number of good cells and bad cells after each cycle of  treatment, basically amplifying the starting ratio, till you get to the point where the small number of bad cells remaining are undetectable or deemed statistically insignificant as regards progression of disease process. Meanwhile, these type of meds randomly wipe, like a wet blackboard-rubber, your bodies chronologically built  database of immunity, leaving some bits untouched, other bits in fragments or corrupted and other bits eliminated.

 

All good stuff !

 

Roll-on full genetic therapies.

 

Nick

Edited 15 December, 2015 by Clunkclick

[moley]

I was given a course of methotrexate in the late '70's along with a course of radiation. The methotrexate made we feel sick for the first few days, but that passed and I don't recall any other problems.

[skomaz]

I've not had it personally but e more in law has for a similar arthritis issue. She took it for quite a while but was closely monitored by e consultant IIRC with regular blood tests etc. However, from. What I recall she did not suffer any signicant side effects and the treatment was largely successful.

Edited 16 December, 2015 by skomaz

[Clunkclick]

The entry for Giant Cell Arteris in my copy of the Oxford Handbook of Clinical Medicine ( 8th Edition, 2010, p558) states that they should start giving you steroids (They refer to oral prednisolone @ 40-60mg per day) as soon as they suspect GCA (Because of the risk of loss of vision) and that, typically, it runs a 2 -year course, before complete remission. Apparently the steroid dose can, dependent on symptoms,  be reduced after 5-7 days, and, if necessary increased again if there's a flare-up. It also refers to gastric and bone protection (Whilst on steroids, Proton Pump Inhibitor and Alendronate).

 

Two years is a long-time to be on a chemo agent like MTX - my therapy was 18 weeks.

 

 

Nick

[swedishskoda]

Thanks, everyone!

 

As Clunkclick said, steroids (or cortisone in daily Swedish parlance) is the standard treatment for GCA, with high initial dosage (I started on 80 mg/day, now on 60), to be reduced successively (to 5 mg/day after 4-5 months and then continued treatment for another 18 months or so).

 

And as  Clunkclick also points out, treatment with steroids, as well as with chemotherapy drugs, is a bit like using a shotgun, targeting the good with the bad. Which is, of course, why my rheumatologist wants to reduce the steroid dose ASAP.

 

As I understand it, MTX is given in much smaller dosage (7-10 mg/week) against autoimmune diseases (psoriasis, rheumatoid diseases) than in cancer therapy. There's a risk for liver damage and other things, but this must be weighed against the risks of steroid treatment.

 

I will be carefully monitored with regular blood tests, not worried about that part. All in all I've been impressed by our Swedish NHS system. The A&E on a Sunday was the only negative experience - the first checks by nurses were done quickly, but I had to wait for seven hours to meet a doctor. After that, however, care was excellent. I got a bed and spent 10 days in hospital, all kinds of examinations (three CT scans, biopsies, bone marrow samples, eye check) in order to get a proper diagnosis. And constant follow-up after my returning home.

 

And being on sick leave for the rest of the year is quite pleasant for a change. Daily walks, time to configure my new PC and practicing a bit on my vintage archtop guitar. And of course enjoying Briskoda.

Edited 16 December, 2015 by swedishskoda

[Clunkclick]

The issue of GCA rings familial bells with me 'cause my dad had this back in the late '90's.

 

It manifested itself with temporal  inflammation and pain at first. I think he attended the GP but, I suspect,  wasn't given any treatment - he was in his mid 70's at the time (Don't you luv UK health policy, and its macro-economic centricity ?).

 

Despite getting additional symptoms, including partial temporary vision field loss and visual  "Floaters" he lived with it for the next year before having a sub-arachnoid haemorrage.

 

Again we were deeply impressed by the way the local hospital he was admitted to (In fact the same one I am currently attending)  treated him - he was just dumped on a sparesly occupied Geriatric ward and left to usual treatment that is so often reported in the UK press - no water, no food. At least they were consistent, because two years earlier they had declared a false negative on a prostate bioposy and had told him, when they subsequently did a case review 18 months later,  that the result should have been reported as a positive  and that it had metasised to the bones !. Outstanding !

 

Since that date, in my "Off" moments, I've always referred to the NHS as the National Death Service.

 

Anyway, family rescued him  from there and he was  transferred to  the UK's Neurological "Centre of Excellence" in London, where it was touch-and-go for a few weeks but unfortunately, after a "Cure" (A lot of drilling of the skull) had been effected he was then re-admitted to another provincial hospital, noted for its neurological proficiency,  where it was learned that the re-occurrence had most likely happened because the "National Centre of Excellence" hadn't followed "Best practice" in the recovery phase and had failed to maintain a tilted bed platform. When they applied that regime, he was OK and went on despite multiple conditions, cardiac, metasised prostate cancer and GCA for a further six years.

 

That aside, glad to see the Swedish Health Care system is on the ball and unconstrained by any of the  hidden agendas which restrict available treatment in the UK . . . for whatever reason.

 

You've probably been given the SP on all of this, but for what its worth, here's the info on GCA from my copy of the Oxford Handbook of Immunolgy and Allergy ( 3rd edition, 2013, P 322).

 

Apparently its exclusively a Caucasian disease, mainly associated with the elderly (Peak incidence in the over '70s).  Female predominance 3:1. Rare in Blacks |( Is it because ize white ?) Incidence  170 per million, with a known association with HLA- DR4 (Presume that's a gene). Cause unknown, but may be associated with Myleoid Leukaemia and HTLV-1 infection. "Limited clonality of T cells suggests localised antigenic stimulus" and "Macrophages produce high levels of IL-1 and IL-6" (Not too sure about the full meaning of those two phrases !)

 

It states that typical presentation of GCA is with headache, fever, and anaemia. Temporal arteries are often swollen, red and tender. Other features include, jaw/tongue claudication (Due to the arteries becoming blocked/narrow), sudden blindness (Due to retinal artery occlusion or cortical blindness), extra ocular muscle palsies (Muscle twitch round the eyes), ischaemic symptoms in arms or legs ( Watch it if you travel by air), stroke, myocardial infarction, inflammatory aneuryisms of the aorta and large branches, pyrexia (Getting hot and bothered) of unknown origin.

 

The text distinguishes GCA from Temporal arteritis on the grounds that the former is a systemic vasculitis whereas the latter is localised.

 

It also mentions Polmyaglia Rheumatica and says symptoms of this include limb girdle pain (?), marked morning stiffness and mild synovitis (Without erosive disease - thank goodness for that !)

 

Again, sounds like a real MoFo of a disease of the elderly.

 

Diagnosis:

No specific immunological tests !

Temporal artery biopsy backs-up diagnosis.

Apparently the presence of Pan-arteritis (??), infiltrate of T-Cells  (PredominantlyCD4 T cells - wrecking ball of the immune system ?) and macrophages (The cells that gobble-up foreign bodies once spotted by the immune system) with giant cells.

Pre-treatment, for up to a week, with steroids will not abolish typical apperances (Their words !).

Scanning (MRI) and  angiography (MRA) may be required to delineate the extent of the disease in the major vessels (Aorta and branches).

Acute-phase response (C- Reactive protein(CRP) and erythrocyte sedimentation rate (ESR)) is marked - **Both of those parameters are available through blood-test** - apparently, occasional patients lack an acute phase response, despite evidence of disease in biopsy.

 

Normochronic normocytic anaemia is usual (Euh ?)

Immunoglobulins and complement are normal.

 

 

Treatment:

 

For GCA, high-dose steroids (60-100mg/day, initially), which are reduced rapidly to maintenance levels (7.5-10mg daily) and continued for 18-24 months - **My R-CHOP therapy included steroids @ 100mg daily for the first five days of each cycle, and I hated the ****** things with a venegance usually reserved for beta-blockers. Kept on getting momentary hallucinations **.

 

The minimum required to keep the disease suppressed is used, as determined by the acute-phase response.

CRP is more useful for monitoring that ESR.

 

Apparently, if steroids fail to control the disease then they employ cytotoxic agents such as azathioprine or Cyclophosphamide ( Used as the principal wrecking ball in my R-CHOP therapy, a chemical relative of mustard gas).

 

Treatment of PMY in the absence of GCA requires lower dose steroids <20mg day.

 

The disease usually burns out  (if they use Cyclophosphamide, that would be "Is burned out" !) over several years and treatment can be withdrawn - although some cases grumble on for longer periods.

 

 

 

Nick

Edited 16 December, 2015 by Clunkclick

[swedishskoda]

@Clunkclick: Thanks for sharing your father's story and the information.

 

I wish I could say that Swedish health care was "unconstrained by any of the  hidden agendas which restrict available treatment". It's not - we have our share of cheeseparing politicians and administrators. But there are still quite a few doctors around that put the patient first and order examinations and lab tests without bothering about the price tag.

 

For me it started with headache, a temperature, and a bit of muscle pain - resembling a common flu. Then a bit of pleural effusion, indicating a bacterial infection. Then I lost vision on my left eye for five minutes, as if someone had poured milk into the eye globe. Scary, and what took me to the A&E. But I should count myself lucky that it was temporary, permanent damage is not uncommon.

 

Their first step was to check for (and rule out) signs of a stroke or haemorrage in the brain. Second hypothesis (CRP level and pleural effusion): bacterial infection, so I got three daliy shots of antibiotics but CRP remained high. Then they switched to steroids and started on the GCA/TA track. Symptoms disappeared, although slowly. A temporal artery biopsy didn't show anything, but it can only confirm TA (if traces found), not rule out. So right now the case is "since medication seems to work, we're probably on the right track".

 

As you say, it's treatable/curable even if it takes some time, and with regular checks and blood tests I'll hopefully avoid the more sinister complications.

 

Your mentioning of the tilted bed platform was interesting. At the hospital I found it comfortable to sleep with ,y head raised, and I've continued to do so back home (the missus and I got ourself adjustable beds a few years ago). Maybe a good thing?

 

I do hope your own chemotherapy has been efficient. Cancer sucks. I'm on regular checks for bladder tumours, having had two removed surgically. Thankfully of the least aggressive kind, so surgery alone has been enough. But they tend to recur.

Edited 16 December, 2015 by swedishskoda

[Clunkclick]

Over here Dave's lot introduced a time standard for the treatment of cancer - basically a maximum of two months from the issue of the GP referral letter to cancer treatment starting. Even though Non-Hodgkin's Diffuse Large B-cell Lymphoma (What I've got) is supposed to be moderately aggressive, the start of my treatment  just about crept in within this time limit.

 

Out of interest what was the time-line for your treatment ?

 

I'm scheduled to have the closing CT/PET scan tomorrow and I'm feeling like pants at the moment.

 

Very much hope your therapy takes you to the pleasant uplands of rude health, asap.

 

 

Nick

 

 

[swedishskoda]

Time limit - you mean for my cancer treatment?

Swedish time standards for health care are:

contact with your primary healt care unit: same day

meeting your GP: within a week

first contact with specialist clinic if needed: within 90 days

specialist treatment/surgery within another 90 days

 

So in theory you can have to wait for 6 months, and if you're unlucky even longer due to shortage of staff/beds and so on.

I was lucky back in 2013 when a bladder tumour was first diagnosed. Noticed blood clots in the urine by the end of June, met my  GP within a week, surgery last week in August. But a TURB (trans-uretral resection of bladder tumour) is a small surgery, takes less than an hour and you can be back home the same day.

 

I'll keep my fingers crossed  for you tomorrow.

Edited 16 December, 2015 by swedishskoda

[Bigeater]

I started taking methotrexate in September last year, after other attempts to help me with psoriasis failed.

I haven't had any side effects, but I do have to go for regular blood tests to make sure I haven't got liver damage.

So good so far. A great combat against it, but i'm constantly advised to avoid sunlight and alcohol.

I'm on 12.5mg a week, or should I say I was, because my wife was diagnosed with the c19 virus in march.

It was at this point that my dermatologist at the hospital told me I should stop taking the drug because it suppresses your immune system.

My employer also sent me home to isolate for 2 weeks, so I'm working from home.

I've been off methotrexate for about 6 weeks now, and the psoriasis has come back with a vengeance.

5 weeks or so ago, I was doing some diy and I accidentally chopped a finger off. It's been reattached but the injury to my hand isn't healing as well.

The psoriasis has real 'got' to that hand, and the skin in the palm of my hand has gone rock hard and so have my fingers. I can't bend them.

My gp has prescribed anti biotics, but they haven't worked.

I have sent pictures of my hand to my dermatologist, and she says they wont put me back on methotrexate until the infection goes away.

So now i'm going round in circles with the NHS. I've got a doctor giving me antibiotics for an infection that wont go away, and another specialist saying they wont see me until the infection has gone. FFS.

I'm going back to the hand hospital today to have my bandages changed and then some physio for my hand.

That'll be a waste of time because my fingers don't bend. Im hoping they insist that dermatology sort me out, and put me back on methotrexate so I can get on with my life.

I've got car projects to do, and cant do them with one hand

 

[moley]

I was on Methotrexate in the late '70's to treat psoriasis and it made me quite ill for the first few days. The psoriasis is in my finger nails and the Methotrexate didn't make them any better. 

[Ttaskmaster]

Wow, necroposts...

 

I used to work in the rheumatology dept at Northwick Park, though not a medical professional my own self.

MTX was a very common addition to all the various steroids, NSAIDs and biological therapies (Anti-TNFα) that patients were on. Some were fine, some had a few issues, some suffered horrifically. It seemed to be just a roll of the dice as to how it affected you personally, really... Our youngest patient was a nurse herself and was just 21, but had serious degredation and she really suffered. Patients with ankylosing spondylitis seemed to fare a bit better, though.

 

 

[Bigeater]

I've been back on the mtxate for a few weeks now, and it's working a treat with no ill feeling.

I've also been and hand my hand peeled like a potato to get rid of the hard skin. It feels so much better.

Thankyou NHS.