The 1995 Kloppenburg Study (New Presentation)

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The 1995 Kloppenburg Study

Kloppenburg, M, Mattie, H, Douwes, N, Dijkmans, BAC, Breedveld, FC,

Minocycline in the Treatment of Rheumatoid Arthritis: Relationship of

Serum Concentrations to Efficacy, Journal of Rheumatology, 1995, 22:4,

611-616.

Objective:

To determine the relationship between blood serum concentrations of

Minocycline and both the clinical efficacy and the incidence of toxicity

when Minocycline is used for the treatment of patients with Rheumatoid

Arthritis.

Results:

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

72.5% of the patients completed the 26 weeks of the trial with no dose

reduction.

15% of the patients had a dose reduction to 100 mg daily because of

adverse effects.

12.5% of the patients withdrew from the trial during the first 4 weeks

due to adverse effects.

Higher blood concentrations of Minocycline lead to better results.

The blood concentrations of Minocycline are different for each person.

No individual difference can explain the variations in the blood

concentrations of Minocycline, although this is in contrast with earlier

studies that have described a correlation with body size or sex.

Description:

80 patients who had definite or classical Rheumatoid Arthritis,

according to the 1958 criteria of the American Rheumatism Association,

were admitted to the 26-week prospective, double blind, placebo

controlled trial if they had an active disease and were being or had

been treated with at least one Disease Modifying Anti Rheumatic Drug

(DMARD).

Minocycline (100 mg twice a day) or placebo was given as adjuvant

therapy. The concomitant dose of DMARD or corticosteroids had to be

stable for at least 3 months. No alteration was allowed in the use of

corticosteroids and DMARD during the trial. In case of serious adverse

effects, as judged by 2 physicians, the daily dosage was reduced to 100

mg; if dosage reduction did not lead to a decrease in severity of the

gastro-intestinal adverse effects, including nausea, to a level that was

tolerated by the patient or did not lead to a total disappearance of the

vestibular adverse effects (dizziness, vertigo, postural unsteadiness),

the study medication was discontinued.

40 patients with active RA were administered minocycline. 29 patients

(72.5%) completed the 26 weeks of the trial at a dose of 100 mg

minocycline twice a day. 6 patients (15%) had a dose reduction to 100 mg

daily because of adverse effects; the dose reduction led to a reduction

in the adverse effects. There were 5 premature discontinuations (12.5%)

during the first 4 weeks of the trial due to adverse effects.

At page 613, the Kloppenburg study states:

" Correlation between estimated concentrations and patient

characteristics: To analyse the possible causes of the variations

between the minocycline concentrations explained by the patient effect,

we analysed several patient characteristics, including sex, age,

duration of RA, body weight, creatinine clearance and the use of another

DMARD simultaneously with minocycline. In a multivariate ANOVA these

characteristics were analysed separately for each characteristic. No

statistically significant contribution to the variation could be

demonstrated for any of these characteristics. "

At page 614, the Kloppenburg study adds:

" Moreover, as expected the variations in the serum concentrations of

minocycline between the patients were significant, as were the effects

of dose and time. In our study there were no patient characteristics

that could explain the variation in the serum concentrations. This is in

contrast with earlier studies that have described a correlation with

body size or sex. "

At page 615, the Kloppenburg study concludes:

" Our results suggest a relationship between the level of serum

concentrations of minocycline and the clinical response, as expressed by

the Ritchie articular index and the number of swollen joints. No

relationship was found between the serum concentrations of minocycline

and the incidence of toxicity. "

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