A randomized, double-blinded, placebo-controlled clinical trial of LY333013, a selective inhibitor of group II secretory phospholipase A2, in the treatment of rheumatoid arthritis.
OBJECTIVE
To evaluate the efficacy and safety of a selective inhibitor of secretory phospholipase (sPLA2), LY333013, in the treatment of rheumatoid arthritis (RA).


METHODS
Two hundred and fifty-one patients with active RA despite treatment with one or more disease modifying antirheumatic drugs (DMARD) received oral doses of LY333013 (50, 250, and 1000 mg) or placebo once daily for 12 weeks. Concomitant low-dose glucocorticoids (< or = 10 mg/day prednisone equivalent) were allowed. Clinical improvement was assessed using the response criteria of the American College of Rheumatology (ACR20), and safety was evaluated with respect to adverse events and laboratory test abnormalities.


RESULTS
The demographic characteristics of the treatment groups were similar. Dose-response relationships were found for ACR20 responses (p = 0.058) and reductions in C-reactive protein (p = 0.058) at week 1. The proportions of patients with an ACR20 response subsequently increased in all study groups including the placebo group at weeks 4 and 8, and the initial treatment benefit was lost. Adverse events were generally mild in severity and not associated with treatment.


CONCLUSIONS
Treatment with LY333013 for 12 weeks was well tolerated but ineffective as an adjunct to DMARD treatment of active RA.
Bradley
John D
JD
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA. bradleyjd@lilly.com
Dmitrienko
Alexei A
AA
Kivitz
Alan J
AJ
Gluck
Oscar S
OS
Weaver
Arthur L
AL
Wiesenhutter
Craig
C
Myers
Stephen L
SL
Sides
Gregory D
GD
D000085:Acetates / Q000009:adverse effects / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use*; D007651:Keto Acids; D008875:Middle Aged; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D010919:Placebos
D000085:Acetates; D018501:Antirheumatic Agents; D004791:Enzyme Inhibitors; D007211:Indoles; D007651:Keto Acids; D010919:Placebos; C117948:varespladib; D010741:Phospholipases A; D054467:Phospholipases A2