Treatment of Early Seropositive Rheumatoid Arthritis with Minocycline
Four-Year Followup of a Double Blind, Placebo-Controlled Trial

Authors:
James R. O'Dell, Gail Paulsen, Claire E. Haire, Kent Blakely, William Palmer,
Steven Wees, P. James Eckhoff, Lynell W. Klassen, Melvin Churchill,
Deborah Doud, Arthur Weaver, And Gerald F. Moore

The Case for Prescribing Minocycline as a
First Line Therapy for Newly Diagnosed RA Patients

• The newest minocycline/RA paper from the RAIN group (James O'Dell, et al) opens with this statement:
• Rheumatoid arthritis (RA) causes substantial morbidity and mortality and current treatments are suboptimal."
• In light of this statement, the results of this 4 year followup to the original study are startling to all but advocates of antibiotic therapy.

Criteria for the original study:

46 patients with seropositive RA of <1 yr duration: 23 in minocycline group (100 mg. bid); 23 in placebo group for 3-6 months.

• none of the patients had previous DMARD or steroid therapy
• 50% improvement criteria had to be met by 6 mos. or treatment was deemed a failure.

Results:

• 65% of minocycline group met a 50% improvement criteria
• 13% of placebo met a 50% improvement criteria

Of interest:

• In seropositive RA patients, remissions are rare.
• All patients respond best when treated early.
• The study group was destined to have ongoing, aggressive disease with a low rate of spontaneous remission if traditional therapies were used.
• Those in the minocycline group had more frequent remissions and needed fewer DMARDs than those treated with conventional therapies.

This fact adds weight to the case for prescribing antibiotics at diagnosis rather than starting with more traditional DMARDS like MTX and gold with their high potential for toxicity.

"Even though patients who did not see the 50% improvement at 6 months were originally considered failures, followup studies have shown maximal improvement did not occur until at least 9 months and continued to improve as treatment progresses showing even greater improvement at one year...At 4 years of followup, superior (in some cases dramatic) results were observed in the minocycline group."

50% of the minocycline patients never required DMARDs or steroids and 40% fulfilled remission criteria without DMARDs or steroids.

According to Figure 1 in the study, the # of swollen, tender joints averaged 31.5 joints at the start of the study and <5 joints after 18 months of minocycline.

Conclusions of 4 year followup:

1) Maximum benefit from minocycline does not occur until after 1 year of treatment; therefore the original 6 month study results are even more remarkable.

2) Patients with early disease respond better to most therapies. However, there may be a window of opportunity early in RA in which minocycline can produce dramatic benefit.

3) Minocycline may need to be continued indefinitely to remain effective.

4) Few side effects and no episodes of dizziness were observed.

5) Regarding minocycline's mechanism of action, "It is clearly possible that an infectious agent will be shown to play a role in the pathogenesis of RA... whether antibacterial effects (of the drug) are important is unclear, but we certainly cannot rule out this possibility."

• minocycline: 8 out of 20 (40%)
• placebo: 1 out of 18 ( 6%)

• minocycline: 10 out of 20 (50%)
• placebo: 16 out of 18 (89%)