Abstract
This 6- week study was conducted to test the efficacy, safety, and tolerability of rofecoxib (a selective COX- 2 inhibitor) compared to nabumetone (a non- selective NSAID) and placebo in osteoarthritis (OA) patients aged 80 and older. Three hundred forty- one patients, mean age 83 years, were randomized. Allocations were made in an approximately 1:2:1:2 ratio (placebo: 12.5 mg rofecoxib: 25 mg rofecoxib: 1500 mg nabumetone). Least square mean changes from baseline in the primary efficacy endpoint, Patient Global Assessment of Disease Status, were as follows (with negative numbers indicating improvement): - 14.85 mm for placebo; - 25.34 mm for 12.5 mg rofecoxib; - 25.40 mm for 25 mg of rofecoxib; and - 25.95 mm for nabumetone ( p<0.001 for all active treatments vs placebo.) Results from secondary end- points, including the 3 WOMAC sub- scales (pain, stiffness, and disability) and the Investigator Global Assessment of Disease Status, were consistent with those for the primary endpoint. No significant between- group differences were observed in the proportions of patients who discontinued treatment due to either clinical or laboratory adverse experiences. Renal safety (edema and hypertension adverse experiences) was similar for rofecoxib and nabumetone. No gastroduodenal ulcers occurred; however, the demonstration of gastrointestinal risk with rofecoxib or nabumetone was beyond the scope of this trial. We conclude that in patients 80 years and older, rofecoxib, 12.5 mg and 25 mg once daily, demonstrated clinical efficacy for the treatment for OA as did 1500 mg of nabumetone. Rofecoxib and nabumetone were generally well tolerated in this elderly population.
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References
Flynn B.: Rheumatoid arthritis and osteoarthritis. Current and future therapies. Am. Pharm. NS34: 31–42, 1994.
Baum C., Kennedy D.L., Forbes M.B.: Utilization of non steroidal antiinflammatory drugs. Arthritis Rheum. 28: 686–692, 1985.
Murray M.D., Brater D.C.: Nonsteroidal anti-inflammatory drugs. Clin. Geriatr. Med. 6: 365–441, 1990.
Wolfe M.M., Lichtenstein D.R., Gurkirpal S.: Medical progress - Gastrointestinal toxicity of nonsteroidal antiinflammatory drugs. N. Engl. J. Med. 340: 1888–1897, 1999.
Phillips A.C., Polisson R.P., Simon L.S.: NSAIDs and the elderly: toxicity and economic implications. Drugs & Aging 10: 119–129, 1997.
Cannon G.W., Caldwell J.R., Holt P., McLean B., Seidenberg B., Bolognese J., Ehrich E., Mukhopadhyay S., Daniels B., for the Rofecoxib Phase III Protocol 035 Study Group: Rofecoxib, a specific inhibitor of cyclooxygenase 2, with clinical efficacy comparable with that of diclofenac: Results of a one-year, randomized, clinical trial in patients with osteoarthritis of the knee and hip. Arthritis Rheum. 43: 978–987, 2000.
Day R., Morrison B., Luza A., Casteneda O., Strusberg A., Nahir M., Helgetveit K.B., Kress B., Daniels B., Bolognese J., Krupa D., Seidenberg B., Elliot E., for the Rofecoxib/Ibuprofen Comparator Study Group:. A Randomized Trial of the Efficacy and Tolerability of the COX-2 Inhibitor Rofecoxib vs Ibuprofen in Patients with Osteoarthritis. Arch. Intern. Med. 160: 1781–1787, 2000.
Lanza F.L., Rack M.L., Simon T.J., Quan H., Bolognese J.A., Hoover M.E.: Specific inhibition of cyclooxygenase-2 with MK-0966 is associated with less gastroduodenal damage than either aspirin or ibuprofen. Aliment. Pharmacol. Ther. 13: 761–767, 1999.
Laine L., Harper S., Simon T., Bath R., Johanson J., Schwartz H., Stern S., Quan H., Bolognese J., for the Rofecoxib Osteoarthritis Endoscopy Study Group: A randomized trial comparing the effect of rofecoxib, a COX-2 specific inhibitor, to ibuprofen on the gastroduodenal mucosa of osteoarthritis patients. Gastroenterology 117: 776–783, 1999.
Langman M.J., Jensen D.M., Watson D.J., Harper S.E., Zhao P.L., Quan H., Bolognese J.A., Simaon T.J.: Incidence of Upper Gastrointestinal Perforations, Symptomatic Ulcers, Bleeding (PUBs). Rofecoxib Compared to NSAIDs.JAMA 282: 1929–1933, 1999.
Hawkey C., Laine L., Simon T., Beaulieu A., Maldonado-Cocco J., Acevedo E., Shahane A., Quan H., Bolognese J., Mortensen E., for the Rofecoxib Osteoarthritis Endoscopy Multinational Study Group: Comparison of the effect of rofecoxib (a cyclooxygenase 2 inhibitor), ibuprofen, and placebo on the gastroduodenal mucosa of patients with osteoarthritis. A randomized, controlled, double-blind, placebo-controlled trial. Arthritis Rheum. 43: 370–377, 2000.
Sigthorsson G., Crane R., Simon T., Hoover M., Quan H., Bolognese J., Bjarnason I.: COX-2 inhibition with rofecoxib does not increase intestinal permeability in healthy subjects: a double blind crossover study comparing rofecoxib with placebo and indomethacin. Gut 47: 527–532, 2000.
Hunt R.H., Bowen B., Mortensen E.R., Simon T.J., James C., Cagliola A., Quan H., Bolognese J.A.:A randomized trial measuring fecal blood loss after treatment with rofecoxib, ibuprofen, or placebo in healthy subjects. Am. J. Med. 109: 201–206, 2000.
Bombardier C., Laine L., Reicin A., Shapiro D., Burgos-Vargas R., Davis B., Day R., Ferraz M.B., Hawkey C.J., Hochberg M.C., Kvien T.K., Schnitzer T.J., for the VIGOR Study Group: Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. N. Engl. J. Med. 343: 1520–1528, 2000.
Folstein M.F.: Mini-Mental State: A practical method for grading the cognitive state of patients for the clinician. J. Psychiatr. Res. 12: 189–198, 1975.
Bellamy N., Buchanan W.W., Goldsmith C.H., Campbell J., Stitt L.: Validation study of WOMAC: A health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J. Rheumatol. 15: 1833–1840, 1988.
Morgan G.J., Poland M., DeLapp R.E.: Efficacy and safety of nabumetone versus diclofenac, naproxen, ibuprofen, and piroxicam in the elderly. Am. J. Med. 95: 19S–27S, 1993.
Munzel P., Lemmel E.E.: Efficacy and safety of nabumetone in 4,541 elderly patients from a drug monitoring study. Drugs 40 (Suppl. 5): 62–64, 1990.
Roth S.H., Tindall E.A., Jain A.K., McMahon G., April P.A., Bockow B.I., Cohen S.B., Fleishmann R.M.:A controlled study comparing the effects of nabumetone, ibuprofen, and ibuprofen plus misoprostol on the upper gastrointestinal tract mucosa. Arch. Intern. Med. 153: 2565–2571, 1993.
Rochon P.A., Fortin P.R., Dear K.B.G., Minaker K.L., Chalmers T.C.: Reporting of age data in clinical trials of arthritis. Deficiencies and solutions. Arch. Intern. Med. 153: 243–248, 1993.
Hamerman D.: Aging and the musculoskeletal system. Ann. Rheum. Dis. 56: 578–585, 1997.
Lipsky P.E., Brooks P., Crofford L.J., Du Bois R., Graham D., Simon L.S., van de Putte L.B., Abramson S.B.: Unresolved issuesinthe role of cyclooxygenase-2in normal physiologic processes and disease. Arch. Intern. Med. 160: 913–920, 2000.
Greenberg H.E., Gillen L.P., Dorval E.P., Huntington M., Wong P., Wildonger L., Larson P., Gottesdiener K.M., Waldman S.A.: MK-0966, a cyclooxygenase inhibitor, has no effect on the anti-platelet activities of low-dose aspirin, measured by serum thromboxane B2 and platelet aggregation. Clin. Pharm. Therapeut. 65: Abstract PII–66, 1999.
Whelton A., Hamilton C.W.: Nonsteroidal anti-inflammatory drugs: effects on kidney function. J. Clin. Pharmacol. 31: 588–598, 1991.
Ruiz J.G., Lowenthal D.T.: NSAIDs and nephrotoxicity in the elderly. Geriatr. Nephrol. Urol. 7: 51–57, 1997.
de Leeuw P.W.: Nonsteroidal Anti-inflammatory Drugs and Hypertension - The Risks in Perspective. Drugs 51: 179–187, 1996.
Brater D.C.: Effects of Nonsteroidal Anti-inflammatory Drugs of Renal function: Focus of Cyclooxygenase-2-Selective Inhibition. Am. J. Med. 107: 65S–71S, 1999.
Johnson A.G., Nguyen T.V., Dayai R.O.: Do nonsteroidal antiinflammatory drugs affect blood pressure? Ann. Intern. Med. 121: 289–300, 1994.
Romero J.C., Dunlap C.L., Strong C.G.: The effect of indomethacin and other anti-inflammatory drugs on the reninangiotensin system. J. Clin. Invest. 58: 282–288, 1976.
Stillman M.T., Schlesinger P.A.: Nonsteroidal anti-inflammatory drug nephrotoxicity. Should we be concerned? Arch. Intern. Med. 150: 268–270, 1990.
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Information in this manuscript was presented in part at the 1999 Annual European Congress of Rheumatology (EULAR). Investigators and centers participating in this trial are listed in the Appendix.
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Truitt, K.E., Sperling, R.S., Ettinger, W.H. et al. A multicenter, randomized, controlled trial to evaluate the safety profile, tolerability, and efficacy of rofecoxib in advanced elderly patients with osteoarthritis. Aging Clin Exp Res 13, 112–121 (2001). https://doi.org/10.1007/BF03351533
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DOI: https://doi.org/10.1007/BF03351533