Prolonged administration of doxycycline in patients with small asymptomatic abdominal aortic aneurysms: report of a prospective (Phase II) multicenter study.
BACKGROUND
The primary purpose of this study was to evaluate compliance, side effects, and safety associated with prolonged administration of doxycycline in patients with small asymptomatic abdominal aortic aneurysms (AAAs). A secondary goal was to determine how treatment with doxycycline influences circulating levels of matrix metalloproteinase-9 (MMP-9) in this patient population.


METHODS
Thirty-six patients with AAAs (30 men and 6 women; mean age, 69 +/- 1 years) were enrolled into a 6-month phase II study to evaluate treatment with doxycycline (100 mg orally twice a day). Aneurysm size was measured before and after treatment, and compliance and side effects were monitored. Plasma levels of doxycycline were measured midway through the study, and plasma MMP-9 concentrations were measured at baseline, 3 months, and 6 months.


RESULTS
Thirty-three of the 36 patients (92%) completed 6 months of doxycycline treatment. Significant treatment-related side effects occurred in five patients (13.9%), including three with cutaneous photosensitivity reactions (8.3%), one with tooth discoloration (2.8%), and one with yeast infection (2.8%). A high rate of compliance with treatment was seen, despite minor but frequent side effects, including nonspecific gastrointestinal symptoms (25%), easily managed episodes of photosensitivity (22.2%), and reversible tooth discoloration (5.5%). The mean plasma doxycycline level after 3 months was 4.62 +/- 0.68 ug/mL (median, 3.64 microg/mL; range, 1.31 to 14.39 microg/mL; n = 23 patients). No significant change was seen in AAA diameter (42.7 +/- 1.3 mm at 6 months versus 41.0 +/- 0.9 mm at baseline), and the overall rate of AAA expansion was 0.63% +/- 0.25% per month. The mean plasma MMP-9 level (n = 19 patients) was elevated at baseline (118.9 +/- 37.9 ng/mL; upper limit of normal, 85 ng/mL) but subsequently decreased to 83.8 +/- 32.9 ng/mL at 3 months (not significant versus baseline) and to 66.4 +/- 24.2 ng/mL at 6 months (P =.022 versus baseline). Only 21% of patients had an elevated level of plasma MMP-9 after 6 months of treatment compared with 47% at baseline (P <.05).


CONCLUSIONS
Prolonged administration of doxycycline is safe and well tolerated by patients with small asymptomatic AAAs and is associated with a gradual reduction in plasma MMP-9 levels. Further studies are needed to evaluate the long-term effects of doxycycline on the rate and extent of aneurysm growth and the potential use of plasma MMP-9 levels as a biomarker of aneurysm disease progression.
Baxter
B Timothy
BT
Department of Surgery, University of Nebraska Medical Center, Omaha, USA.
Pearce
William H
WH
Waltke
Eugene A
EA
Littooy
Fred N
FN
Hallett
John W
JW
Kent
K Craig
KC
Upchurch
Gilbert R
GR
Chaikof
Elliot L
EL
Mills
Joseph L
JL
Fleckten
Beverly
B
Longo
G Matt
GM
Lee
Jason K
JK
Thompson
Robert W
RW
D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D017544:Aortic Aneurysm, Abdominal / Q000188:drug therapy*; D015415:Biomarkers / Q000097:blood; D018450:Disease Progression; D004318:Doxycycline / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood / Q000187:drug effects; D008875:Middle Aged; D010349:Patient Compliance; D011446:Prospective Studies; D013223:Statistics as Topic; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D015415:Biomarkers; D020780:Matrix Metalloproteinase 9; D004318:Doxycycline