Dr. response to O'Dell's follow-up

[Guest guest]

I was browsing alt.support.arthritis and noticed this and thought you might want

to see it. Response to it is from Dr. Hoch who hangs out there.

Mark

" This month's issue of Arthritis and Rheumatism carries the four year followup

of Jame's O'Dell's study of minocycline in the treatment of early seropositive

rheumatoid arthritid. I think this is an important article and hope that all of

us can appreciate what this article says and what it doesn't say without the

usual flames from the usual suspects.

Dr O'Dell and associates reported on their followup of the 46 patients who they

originally treated either with minocycline 100 mg twice a day or placebo for 3

to 6 months. In the original study, if the patients did not have 50%

improvement at 3 months, they were withdrawn from the blinded part of the study.

The patients that remained in the blinded portion were then reevaluated after

another 3 months. At that time the blinded portion of the study was stopped and

the patient's physician was free to treat the patient as he or she wished. If

the patient had been on minocycline and had a good response (15 of 23 patients)

minocycline was restarted in most cases.

This open followup study then went on for the next 3 and 1/2 years. In this

paper, they report what happened to these patients. They went back and found 20

of the original minocycline patients and 18 of the original 23 placebo patients.

During the blinded period, no one receiving minocycline withdrew because of

toxicity. One placebo patient withdrew because of a GI bleed. In the open

phase, 3 of the minocycline patients discontinued minocycline because of

hyperpigmentation skin changes and

1 reported mild hyperpigmentation but continued the drug. In the three patients

who stopped, the pigmentation disappeared over time.

The mean years of followup for the minocycline patients (20 patients) was 3.8

years. It was 4 years for the 18 placebo patients.

For purposes of this study, minocycline was not considered a DMARD although as

you will see this study suggests it is. There was a significant difference in

the number of patients in remission in the minocycline for 6 months versus the

placebo group for 6 months. Only 1 of 18 placebo patients was in remission

without the usual DMARDs.

This gives a figure of about a 6% chance of a spontaneous remission for early

RA. That is interesting because we always use a 5% figure to tell patients what

their chance of a spontaneous remission in early disease is. In comparison, 8

of the 20 minocycline patients were in remission at the time of evaluation

without other DMARDs or steroids.

The converse was also true. Only 10 of 20 patients (50%) who received

minocycline required other DMARDs at 4 years as compared to 16 of 18 (89%)

placebo patients. With regard to prednisone use 9 of 20 minocycline patients

were on prednisone (45%) as compared to 11 of 18 placebo patients (65%). At the

end of the 3 and 1/2 year open label study, 11 of 20 minocycline patients

remained on minocycline and 4 of the placebo group were now on minocycline.

When they looked at the time course of response, while significant response had

occured by 3 months, maximal response did not occur until at least 9 months.

In their discussion, the authors point out that their results differ

dramatically from the MIRA and Netherland trials. One possible reason may be

that their disease duration was less than 5 months on the average whereas

Netherlands was a mean of 8.6 years and MIRA 13 years.

They also discuss that they have not data on the mechanism of action of

minocycline but speculate that it may inhibit metalloproteinases rather than

being antibacterial.

They also stated that because of the side effect of hyperpigmentation, they have

switched some of their patients to doxycycline (for which there is no data on

efficacy but it does cause less hyperpigmentation.

Now, what's the take home in my opinion.

This study certainly suggests that minocycline is a reasonable option for

patients with early rheumatoid arthritis. Unfortunately we do not have any

early data to directly compare it to other DMARDs but it is certainly preferable

to just giving a patient NSAIDs or Prednisone as some physicians appear still to

be doing. Certainly, at the least, in my opinion, a patient with early RA

should be offered an NSAID AND minocycline unless there is some contraindication

like pregnancy or allergy.

This study does not consider xray change over time.

No conclusion can be made as to the infectious cause of rheumatoid arthritis

from this study.

No statement can be made that minocycline cures RA from this study.

No comparison with other DMARDs or combinations can be made.

II should remind you that, despite minocycline, 45% of the patients still

required steroids and 50% required an additional DMARD.

These are no large numbers.

Nevertheless, I believe it is an important study and should alter how physicians

view early rheumatoid arthritis