RESEARCH - Should tetracycline treatment be used more extensively for RA?

[Guest guest]

J Rheumatol. 2003 Oct;30(10):2112-22.Links

Comment in:

J Rheumatol. 2003 Oct;30(10):2085-7.

Should tetracycline treatment be used more extensively for rheumatoid

arthritis? Metaanalysis demonstrates clinical benefit with reduction

in disease activity.Stone M, Fortin PR, Pacheco-Tena C, Inman RD.

Division of Rheumatology, Department of Medicine, Toronto Western

Hospital, 399 Bathurst Street, Toronto, Ontario M5T 2S8, Canada.

OBJECTIVE: To compare the effectiveness of tetracycline antibiotics

versus control (placebo or conventional treatment) in rheumatoid

arthritis (RA) for the reduction of disease activity as defined by

American College of Rheumatology criteria. METHODS: We searched

Medline (1966-February 2002), Embase (1980-February 2002), and the

Cochrane Controlled Trials Register (Issue 1, 2002 Cochrane Library).

Reference lists of published trials were searched by hand for further

identification of published reports and presentations at scientific

meetings. Randomized controlled trials comparing tetracyclines to

control (placebo or conventional disease modifying antirheumatic

therapy) were selected for inclusion if at least one of the following

outcomes was reported: tender joint count (TJC), swollen joint count,

patient pain score by visual analog scale, patient global assessment

of disease activity, physician global assessment of disease activity,

eosinophil sedimentation rate (ESR) and C-reactive protein (CRP),

joint space narrowing and erosions, adverse events, and quality of

life as measured by the Health Assessment Questionnaire. Subjects were

required to have RA as defined by the 1987 ARA criteria. RESULTS: Ten

randomized controlled trials including 535 individuals were reviewed.

Only 3 trials were considered high quality; elements of bias could not

be excluded in the remainder. Tetracyclines, when administered for >

or = 3 months, were associated with a significant reduction in disease

activity in RA as follows: for TJC, standardized mean difference (SMD)

= -0.39, 95% CI -0.74, -0.05; and for acute phase reactants, ESR, SMD

= -8.96, 95% CI -14.51, -3.42. The treatment effect was more marked in

the subgroup of patients with disease duration < 1 year who were

seropositive. There was no absolute increased risk of adverse events

associated with tetracyclines: absolute risk difference = 0.10, 95%

confidence interval (CI) -0.01, 0.21. No beneficial effect was seen on

radiological progression of disease: for erosions, SMD = 0.17, 95% CI

-0.29, 0.64. In addition, subgroup analysis excluding trials with

doxycycline showed that minocycline alone had a greater effect on

reduction of disease activity: for TJC, SMD = -0.69, 95% CI -0.89,

-0.49; and for ESR, SMD = -10.14, 95% CI -14.72, -5.57. CONCLUSION:

Tetracyclines, in particular minocycline, were associated with a

clinically significant improvement in disease activity in RA with no

absolute increased risk of side effects. Unfortunately, the

information available was inadequate to allow a detailed analysis of

individual side effects in the studies. Further research is warranted

to compare these agents to newer disease modifying drugs for

comparable safety, efficacy, and cost-effectiveness.

PMID: 14528503

J Rheumatol. 2003 Oct;30(10):2112-22.Links

Comment in:

J Rheumatol. 2003 Oct;30(10):2085-7.

Should tetracycline treatment be used more extensively for rheumatoid

arthritis? Metaanalysis demonstrates clinical benefit with reduction

in disease activity.

Stone M, Fortin PR, Pacheco-Tena C, Inman RD.

Division of Rheumatology, Department of Medicine, Toronto Western

Hospital, 399 Bathurst Street, Toronto, Ontario M5T 2S8, Canada.

OBJECTIVE: To compare the effectiveness of tetracycline antibiotics

versus control (placebo or conventional treatment) in rheumatoid

arthritis (RA) for the reduction of disease activity as defined by

American College of Rheumatology criteria.

METHODS: We searched Medline (1966-February 2002), Embase

(1980-February 2002), and the Cochrane Controlled Trials Register

(Issue 1, 2002 Cochrane Library). Reference lists of published trials

were searched by hand for further identification of published reports

and presentations at scientific meetings. Randomized controlled trials

comparing tetracyclines to control (placebo or conventional disease

modifying antirheumatic therapy) were selected for inclusion if at

least one of the following outcomes was reported: tender joint count

(TJC), swollen joint count, patient pain score by visual analog scale,

patient global assessment of disease activity, physician global

assessment of disease activity, eosinophil sedimentation rate (ESR)

and C-reactive protein (CRP), joint space narrowing and erosions,

adverse events, and quality of life as measured by the Health

Assessment Questionnaire. Subjects were required to have RA as defined

by the 1987 ARA criteria.

RESULTS: Ten randomized controlled trials including 535 individuals

were reviewed. Only 3 trials were considered high quality; elements of

bias could not be excluded in the remainder. Tetracyclines, when

administered for > or = 3 months, were associated with a significant

reduction in disease activity in RA as follows: for TJC, standardized

mean difference (SMD) = -0.39, 95% CI -0.74, -0.05; and for acute

phase reactants, ESR, SMD = -8.96, 95% CI -14.51, -3.42. The treatment

effect was more marked in the subgroup of patients with disease

duration < 1 year who were seropositive. There was no absolute

increased risk of adverse events associated with tetracyclines:

absolute risk difference = 0.10, 95% confidence interval (CI) -0.01,

0.21. No beneficial effect was seen on radiological progression of

disease: for erosions, SMD = 0.17, 95% CI -0.29, 0.64. In addition,

subgroup analysis excluding trials with doxycycline showed that

minocycline alone had a greater effect on reduction of disease

activity: for TJC, SMD = -0.69, 95% CI -0.89, -0.49; and for ESR, SMD

= -10.14, 95% CI -14.72, -5.57.

CONCLUSION: Tetracyclines, in particular minocycline, were associated

with a clinically significant improvement in disease activity in RA

with no absolute increased risk of side effects. Unfortunately, the

information available was inadequate to allow a detailed analysis of

individual side effects in the studies. Further research is warranted

to compare these agents to newer disease modifying drugs for

comparable safety, efficacy, and cost-effectiveness.

PMID: 14528503

http://www.ncbi.nlm.nih.gov/pubmed/14528503

Not an MD

[Guest guest]

I'm just putting this here for those that ARE interested - you can do

your own research and from there decide what you feel is right for

you personally and what you can assess from the information at hand.

For anyone who wants to see clinical trials that found Tetracyclines

effective in the treatment of RA the Roadback.org foundation has

summaries of these or any google search will find them.

As you will notice these trials unfortunately are never funded by

drug companies as the drugs are now way past their patent period and

very very inexpensive so the supplying company (anyone can produce

them now) never make anything from them.

Also I'll make mention of these facts known to those who have been

successfully treated and those Professionals that continue to treat

patients with them;

The use of tetracyclines in most studies is not in the regime that

has been successful in actual treatment. ie success is by " pulsing "

the dose (ie not daily dose like in the studies) but " every other

day " ie Mon, Wed Fri etc

For long standing & severe disease it's a longer road than 3 months

before noticeable turnaround and often other things are required such

as killing off high ASO titres (from Strep), use of NSAIDS or

cortisone to reduce swelling so the drug can access the joint,

sometimes intravenous therapy is required, or mixing the different

types, this means actually having to look at each individual as just

that. Not just giving them a pill sending them away and hope that it

works on it's own. Treating 20 patients a day doesn't work with this

therapy. Most of us want instant results - a patient has to want to

go the extra mile.

In newer disease the results appear much more quickly and readily and

remission has even been achieved.

Many patients are fearful of the herxheimer effects as their symptoms

temporarily become worse before they get better - especially if

they're used to symptomatic relief or suppressive drugs that do just

that.

A lot of studies continue the use of methotrexate whilst adding the

tetracyline. This is totally against the antibiotic protocol and

actually works against all that it's known to do - due to it's

suppression of the immune system. You are expected to stop the MXT

well before begining.

All I can say is - just because it's not all over the media are all

these people who have had excellent results with it wrong? Why are

hospitals and labs still forking our their own resourcing to fund

these studies if it doesn't work, even if we don't really know the

full story why?

How many of you have taken this information to their Doc's / Rheumies

(even Pharmacistis) and they look at you dumbfounded? They've never

heard of it? How many drug companies send their reps to these

professionals to update them on this drug? None - they get no $$ for

it as it now can be produced by anyone with very marginal profit.

I just honestly wonder if 14 years ago I walked out of my 1st visit

to my Rheumy with Doxy instead of Gold and Voltaren where i'd

actually be now. I'd have liked to have been given that information

and choice instead of the massive headaches the Gold gave me.

We all deserve to be involved in our own treatment and choices.

That's my more than 20 cents worth!

>

> J Rheumatol. 2003 Oct;30(10):2112-22.Links

>

> Comment in:

> J Rheumatol. 2003 Oct;30(10):2085-7.

> Should tetracycline treatment be used more extensively for

rheumatoid

> arthritis? Metaanalysis demonstrates clinical benefit with reduction

> in disease activity.Stone M, Fortin PR, Pacheco-Tena C, Inman RD.

> Division of Rheumatology, Department of Medicine, Toronto Western

> Hospital, 399 Bathurst Street, Toronto, Ontario M5T 2S8, Canada.

>

> OBJECTIVE: To compare the effectiveness of tetracycline antibiotics

> versus control (placebo or conventional treatment) in rheumatoid

> arthritis (RA) for the reduction of disease activity as defined by

> American College of Rheumatology criteria. METHODS: We searched

> Medline (1966-February 2002), Embase (1980-February 2002), and the

> Cochrane Controlled Trials Register (Issue 1, 2002 Cochrane

Library).

> Reference lists of published trials were searched by hand for

further

> identification of published reports and presentations at scientific

> meetings. Randomized controlled trials comparing tetracyclines to

> control (placebo or conventional disease modifying antirheumatic

> therapy) were selected for inclusion if at least one of the

following

> outcomes was reported: tender joint count (TJC), swollen joint

count,

> patient pain score by visual analog scale, patient global assessment

> of disease activity, physician global assessment of disease

activity,

> eosinophil sedimentation rate (ESR) and C-reactive protein (CRP),

> joint space narrowing and erosions, adverse events, and quality of

> life as measured by the Health Assessment Questionnaire. Subjects

were

> required to have RA as defined by the 1987 ARA criteria. RESULTS:

Ten

> randomized controlled trials including 535 individuals were

reviewed.

> Only 3 trials were considered high quality; elements of bias could

not

> be excluded in the remainder. Tetracyclines, when administered for >

> or = 3 months, were associated with a significant reduction in

disease

> activity in RA as follows: for TJC, standardized mean difference

(SMD)

> = -0.39, 95% CI -0.74, -0.05; and for acute phase reactants, ESR,

SMD

> = -8.96, 95% CI -14.51, -3.42. The treatment effect was more marked

in

> the subgroup of patients with disease duration < 1 year who were

> seropositive. There was no absolute increased risk of adverse events

> associated with tetracyclines: absolute risk difference = 0.10, 95%

> confidence interval (CI) -0.01, 0.21. No beneficial effect was seen

on

> radiological progression of disease: for erosions, SMD = 0.17, 95%

CI

> -0.29, 0.64. In addition, subgroup analysis excluding trials with

> doxycycline showed that minocycline alone had a greater effect on

> reduction of disease activity: for TJC, SMD = -0.69, 95% CI -0.89,

> -0.49; and for ESR, SMD = -10.14, 95% CI -14.72, -5.57. CONCLUSION:

> Tetracyclines, in particular minocycline, were associated with a

> clinically significant improvement in disease activity in RA with no

> absolute increased risk of side effects. Unfortunately, the

> information available was inadequate to allow a detailed analysis of

> individual side effects in the studies. Further research is

warranted

> to compare these agents to newer disease modifying drugs for

> comparable safety, efficacy, and cost-effectiveness.

>

> PMID: 14528503

>

> J Rheumatol. 2003 Oct;30(10):2112-22.Links

>

> Comment in:

> J Rheumatol. 2003 Oct;30(10):2085-7.

>

>

> Should tetracycline treatment be used more extensively for

rheumatoid

> arthritis? Metaanalysis demonstrates clinical benefit with reduction

> in disease activity.

>

>

> Stone M, Fortin PR, Pacheco-Tena C, Inman RD.

> Division of Rheumatology, Department of Medicine, Toronto Western

> Hospital, 399 Bathurst Street, Toronto, Ontario M5T 2S8, Canada.

>

>

> OBJECTIVE: To compare the effectiveness of tetracycline antibiotics

> versus control (placebo or conventional treatment) in rheumatoid

> arthritis (RA) for the reduction of disease activity as defined by

> American College of Rheumatology criteria.

>

> METHODS: We searched Medline (1966-February 2002), Embase

> (1980-February 2002), and the Cochrane Controlled Trials Register

> (Issue 1, 2002 Cochrane Library). Reference lists of published

trials

> were searched by hand for further identification of published

reports

> and presentations at scientific meetings. Randomized controlled

trials

> comparing tetracyclines to control (placebo or conventional disease

> modifying antirheumatic therapy) were selected for inclusion if at

> least one of the following outcomes was reported: tender joint count

> (TJC), swollen joint count, patient pain score by visual analog

scale,

> patient global assessment of disease activity, physician global

> assessment of disease activity, eosinophil sedimentation rate (ESR)

> and C-reactive protein (CRP), joint space narrowing and erosions,

> adverse events, and quality of life as measured by the Health

> Assessment Questionnaire. Subjects were required to have RA as

defined

> by the 1987 ARA criteria.

>

> RESULTS: Ten randomized controlled trials including 535 individuals

> were reviewed. Only 3 trials were considered high quality; elements

of

> bias could not be excluded in the remainder. Tetracyclines, when

> administered for > or = 3 months, were associated with a significant

> reduction in disease activity in RA as follows: for TJC,

standardized

> mean difference (SMD) = -0.39, 95% CI -0.74, -0.05; and for acute

> phase reactants, ESR, SMD = -8.96, 95% CI -14.51, -3.42. The

treatment

> effect was more marked in the subgroup of patients with disease

> duration < 1 year who were seropositive. There was no absolute

> increased risk of adverse events associated with tetracyclines:

> absolute risk difference = 0.10, 95% confidence interval (CI) -0.01,

> 0.21. No beneficial effect was seen on radiological progression of

> disease: for erosions, SMD = 0.17, 95% CI -0.29, 0.64. In addition,

> subgroup analysis excluding trials with doxycycline showed that

> minocycline alone had a greater effect on reduction of disease

> activity: for TJC, SMD = -0.69, 95% CI -0.89, -0.49; and for ESR,

SMD

> = -10.14, 95% CI -14.72, -5.57.

>

> CONCLUSION: Tetracyclines, in particular minocycline, were

associated

> with a clinically significant improvement in disease activity in RA

> with no absolute increased risk of side effects. Unfortunately, the

> information available was inadequate to allow a detailed analysis of

> individual side effects in the studies. Further research is

warranted

> to compare these agents to newer disease modifying drugs for

> comparable safety, efficacy, and cost-effectiveness.

>

>

> PMID: 14528503

>

> http://www.ncbi.nlm.nih.gov/pubmed/14528503

>

>

>

> Not an MD

>