The O'Dell Study (New Presentation)

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The O'Dell Study

O'Dell, JR, Haire, CE, Palmer, W, Drymalski, W, Wees, S, Blakely, K,

Churchill, M, Eckhoff, PJ, Weaver, A, Doud, D, son, N, Dietz, F,

Olson, R, Maloley, P, Klassen, LW, , GF, Treatment of Early

Rheumatoid Arthritis with Minocycline or Placebo: Results of a

Randomized, Double-Blind, Placebo-Controlled Trial, Arthritis &

Rheumatism, 1997, 40:5, 842-848.

Objective:

To determine if Minocycline is an effective therapy for Rheumatoid

Arthritis patients who are RF positive when used within the first year

of the disease.

Results:

The patients took 100 mg of Minocin, twice a day, every day.

No patient withdrew from the study due to toxicity.

No patient reported dizziness that precluded continuation of the

protocol.

65% of the patients improved their symptoms by at least 50% within 3

months.

22% of the patients achieved a remission within 1 year and no longer

received any therapy.

Description:

46 patients with Rheumatoid Arthritis of less than one year in duration

were enrolled in the study. 23 patients were treated with minocycline,

whereas 23 received a matching placebo. The dosage of minocycline was

100 mg twice per day and was constant throughout the study. Patients in

both groups continued their pre-study NSAID treatment at stable doses.

15 of the 23 patients (65%) treated with minocycline and 3 of the 23

patients (13%) treated with placebo improved by at least 50% within 3

months. Within 1 year, 5 of the 23 patients (22%) treated with

minocycline were in remission and no longer received any therapy,

whereas only 1 of the 23 patients (4%) taking a placebo was in remission

and no longer received any therapy.

None of the minocycline-treated patients withdrew due to toxicity. None

of the patients reported dizziness that precluded continuation of the

protocol.

At pages 845-846, the O'Dell study states:

" We believe that several key points about our study design are worth

emphasizing: we enrolled only patients with early disease (these

patients have been shown by many to have the best response to therapy),

we enrolled only patients who were RF positive and thus we were studying

a relatively homogeneous patient population and a group of patients who

were destined to have a low spontaneous remission rate, and finally, we

chose to define success as 50% improvement of symptoms instead of the

20% that is often used.

We believe our results are even more remarkable because our study design

almost certainly decreased the chances of finding a positive effect.

Since we were conducting a placebo-controlled trial, we required 50%

improvement at 3 months as a criterion for continuation in the study. We

did not want to continue placebo treatment for more than 3 months in

patients with active RA. Data from our study and others suggest that

maximum benefit of minocycline does not occur until after 1 year of

therapy. Therefore, we almost certainly lost patients before they had a

maximal response to minocycline. "

At page 846, the O'Dell study adds:

" Minocycline has been shown to have antiinflammatory, immunomodulatory,

and chondroprotective effects in addition to its antibacterial activity.

Tetracyclines, particularly minocycline and doxycycline, are potent

inhibitors of metalloproteinases, including collagenase and gelatinase.

Metalloproteinases are almost certainly active in RA joint destruction,

and studies in animal models of arthritis (both RA and osteoarthritis)

have shown benefit with minocycline or doxycycline treatment. Modified

derivatives of minocycline that retain their ability to inhibit

metalloproteinases but do not have antibacterial effects remain

effective in some of these models. Finally, there has been much recent

enthusiasm for, and some evidence to support the use of, agents with

activity against tumor necrosis factor a [alpha] in the treatment of RA.

Interestingly, tetracyclines, especially minocycline and doxycycline,

inhibit the production of tumor necrosis factor. "

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