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LONG BEACH, CALIF. — A higher rate of adverse events in older patients with knee osteoarthritis treated topically for 12 weeks with an NSAID, compared with placebo, was caused mainly by application-site reactions but included one serious cardiovascular event that might have been related to the drug treatment, a post hoc analysis of data on 538 patients found.
The investigators analyzed data on people aged 65 years and older with symptomatic knee osteoarthritis (433 had comorbid hypertension, diabetes, or cardiovascular disease). Their source was three larger randomized, double-blind trials—two unpublished—that had looked at broader populations. Patients applied 4 g/day of either diclofenac sodium 1% gel (Voltaren) or the drug's vehicle to one painful knee.
One 80-year-old woman with hypertension and diabetes, among the 274 patients on diclofenac sodium 1% gel, developed deep vein thrombosis and pulmonary embolism that possibly was related to treatment, Dr. H. Richard Barthel and his associates reported in a poster presentation.
Overall, 56% of patients on diclofenac gel developed adverse events, compared with 44% of 264 patients treated with placebo gel, added Dr. Barthel, a rheumatologist in Santa Barbara, Calif.
NSAIDs are known to increase risk for cardiovascular or renal problems in a dose-related fashion, especially in older patients and people with hypertension, diabetes, or cardiovascular disease. Topical formulations may reduce this risk by reducing systemic exposure to NSAIDs compared with oral formulations. The ad hoc analysis compared the gel only to placebo, not to oral therapy, and found higher rates of adverse events for the drug vs. placebo.
Application-site reactions occurred in 8.8% on diclofenac gel and 1.1% on placebo. Serious adverse events occurred in 2.6% on diclofenac and 1.1% on placebo. Adverse cardiovascular events were seen in 2.6% on diclofenac and 1.1% on placebo. Adverse renal events were seen in 1.1% on diclofenac and 0.4% on placebo.
Among more common adverse events, 11% of subjects on diclofenac and 10% on placebo reported headache, 8% on diclofenac and 7% on placebo reported arthralgia, and 8% on diclofenac and 6% on placebo reported back pain.
The analysis included 307 patients with hypertension, 84 with diabetes, and 42 with cardiovascular disease. In the hypertension subgroup, adverse events were seen in 54% of 159 people randomized to diclofenac gel, compared with 45% of 148 people using placebo. In the diabetes subgroup, adverse events occurred in 19 (51%) of 37 patients treated with diclofenac and in 21 (48%) of 47 treated with placebo. In the subgroup with cardiovascular disease, adverse events occurred in 15 (56%) of 27 on diclofenac and in 2 (13%) of 15 on placebo, though none developed an adverse cardiovascular event.
Dr. Barthel conducted the study under a research contract for Novartis, which makes Voltaren. His associates in the study were employees of Novartis or of Endo Pharmaceuticals, which markets the drug.
The therapy of osteoarthritis remains insufficient in many patients.
It is particularly problematic in the elderly where there are often
concomitant diseases that limit our options for several of the oral
medications, particularly NSAIDs and potent analgesics. The recent Food
and Drug Administration approval of diclofenac has changed the
therapeutic paradigm. Diclofenac gel 1% has been approved for
osteoarthritis of the knee, hand, and other superficial joints, and
Pennsaid has been approved for osteoarthritis of the knee.
In this posthoc pooled analysis of 538 patients over 65 years of age
treated for 3 months with the diclofenac gel 1% for osteoarthritis of
the knee, we see an increase in irritation at the site of application,
but a minimal increase in adverse events involving blood pressure, renal
function, hepatic dysfunction, and gastrointestinal ulcer disease.
Pharmacokinetic studies have shown that systemic absorption of the
topical diclofenac is 40 times less than oral diclofenac. This improved
safety allows us to provide therapy to patients otherwise unable to
receive anti-inflammatory drugs.
It will be no surprise if the guidelines for therapy of
osteoarthritis from the United States will soon approximate those from
Europe, where topical NSAIDs are part of the therapeutic algorithm for
osteoarthritis.
ROY D. ALTMAN, M.D., is professor of medicine in the division of
rheumatology and immunology at the University of California, Los
Angeles. He has been a consultant to Novartis, Eli Lilly, Ferring
Pharmaceuticals, and Rottapharm/Madaus.
The therapy of osteoarthritis remains insufficient in many patients.
It is particularly problematic in the elderly where there are often
concomitant diseases that limit our options for several of the oral
medications, particularly NSAIDs and potent analgesics. The recent Food
and Drug Administration approval of diclofenac has changed the
therapeutic paradigm. Diclofenac gel 1% has been approved for
osteoarthritis of the knee, hand, and other superficial joints, and
Pennsaid has been approved for osteoarthritis of the knee.
In this posthoc pooled analysis of 538 patients over 65 years of age
treated for 3 months with the diclofenac gel 1% for osteoarthritis of
the knee, we see an increase in irritation at the site of application,
but a minimal increase in adverse events involving blood pressure, renal
function, hepatic dysfunction, and gastrointestinal ulcer disease.
Pharmacokinetic studies have shown that systemic absorption of the
topical diclofenac is 40 times less than oral diclofenac. This improved
safety allows us to provide therapy to patients otherwise unable to
receive anti-inflammatory drugs.
It will be no surprise if the guidelines for therapy of
osteoarthritis from the United States will soon approximate those from
Europe, where topical NSAIDs are part of the therapeutic algorithm for
osteoarthritis.
ROY D. ALTMAN, M.D., is professor of medicine in the division of
rheumatology and immunology at the University of California, Los
Angeles. He has been a consultant to Novartis, Eli Lilly, Ferring
Pharmaceuticals, and Rottapharm/Madaus.
The therapy of osteoarthritis remains insufficient in many patients.
It is particularly problematic in the elderly where there are often
concomitant diseases that limit our options for several of the oral
medications, particularly NSAIDs and potent analgesics. The recent Food
and Drug Administration approval of diclofenac has changed the
therapeutic paradigm. Diclofenac gel 1% has been approved for
osteoarthritis of the knee, hand, and other superficial joints, and
Pennsaid has been approved for osteoarthritis of the knee.
In this posthoc pooled analysis of 538 patients over 65 years of age
treated for 3 months with the diclofenac gel 1% for osteoarthritis of
the knee, we see an increase in irritation at the site of application,
but a minimal increase in adverse events involving blood pressure, renal
function, hepatic dysfunction, and gastrointestinal ulcer disease.
Pharmacokinetic studies have shown that systemic absorption of the
topical diclofenac is 40 times less than oral diclofenac. This improved
safety allows us to provide therapy to patients otherwise unable to
receive anti-inflammatory drugs.
It will be no surprise if the guidelines for therapy of
osteoarthritis from the United States will soon approximate those from
Europe, where topical NSAIDs are part of the therapeutic algorithm for
osteoarthritis.
ROY D. ALTMAN, M.D., is professor of medicine in the division of
rheumatology and immunology at the University of California, Los
Angeles. He has been a consultant to Novartis, Eli Lilly, Ferring
Pharmaceuticals, and Rottapharm/Madaus.
LONG BEACH, CALIF. — A higher rate of adverse events in older patients with knee osteoarthritis treated topically for 12 weeks with an NSAID, compared with placebo, was caused mainly by application-site reactions but included one serious cardiovascular event that might have been related to the drug treatment, a post hoc analysis of data on 538 patients found.
The investigators analyzed data on people aged 65 years and older with symptomatic knee osteoarthritis (433 had comorbid hypertension, diabetes, or cardiovascular disease). Their source was three larger randomized, double-blind trials—two unpublished—that had looked at broader populations. Patients applied 4 g/day of either diclofenac sodium 1% gel (Voltaren) or the drug's vehicle to one painful knee.
One 80-year-old woman with hypertension and diabetes, among the 274 patients on diclofenac sodium 1% gel, developed deep vein thrombosis and pulmonary embolism that possibly was related to treatment, Dr. H. Richard Barthel and his associates reported in a poster presentation.
Overall, 56% of patients on diclofenac gel developed adverse events, compared with 44% of 264 patients treated with placebo gel, added Dr. Barthel, a rheumatologist in Santa Barbara, Calif.
NSAIDs are known to increase risk for cardiovascular or renal problems in a dose-related fashion, especially in older patients and people with hypertension, diabetes, or cardiovascular disease. Topical formulations may reduce this risk by reducing systemic exposure to NSAIDs compared with oral formulations. The ad hoc analysis compared the gel only to placebo, not to oral therapy, and found higher rates of adverse events for the drug vs. placebo.
Application-site reactions occurred in 8.8% on diclofenac gel and 1.1% on placebo. Serious adverse events occurred in 2.6% on diclofenac and 1.1% on placebo. Adverse cardiovascular events were seen in 2.6% on diclofenac and 1.1% on placebo. Adverse renal events were seen in 1.1% on diclofenac and 0.4% on placebo.
Among more common adverse events, 11% of subjects on diclofenac and 10% on placebo reported headache, 8% on diclofenac and 7% on placebo reported arthralgia, and 8% on diclofenac and 6% on placebo reported back pain.
The analysis included 307 patients with hypertension, 84 with diabetes, and 42 with cardiovascular disease. In the hypertension subgroup, adverse events were seen in 54% of 159 people randomized to diclofenac gel, compared with 45% of 148 people using placebo. In the diabetes subgroup, adverse events occurred in 19 (51%) of 37 patients treated with diclofenac and in 21 (48%) of 47 treated with placebo. In the subgroup with cardiovascular disease, adverse events occurred in 15 (56%) of 27 on diclofenac and in 2 (13%) of 15 on placebo, though none developed an adverse cardiovascular event.
Dr. Barthel conducted the study under a research contract for Novartis, which makes Voltaren. His associates in the study were employees of Novartis or of Endo Pharmaceuticals, which markets the drug.
LONG BEACH, CALIF. — A higher rate of adverse events in older patients with knee osteoarthritis treated topically for 12 weeks with an NSAID, compared with placebo, was caused mainly by application-site reactions but included one serious cardiovascular event that might have been related to the drug treatment, a post hoc analysis of data on 538 patients found.
The investigators analyzed data on people aged 65 years and older with symptomatic knee osteoarthritis (433 had comorbid hypertension, diabetes, or cardiovascular disease). Their source was three larger randomized, double-blind trials—two unpublished—that had looked at broader populations. Patients applied 4 g/day of either diclofenac sodium 1% gel (Voltaren) or the drug's vehicle to one painful knee.
One 80-year-old woman with hypertension and diabetes, among the 274 patients on diclofenac sodium 1% gel, developed deep vein thrombosis and pulmonary embolism that possibly was related to treatment, Dr. H. Richard Barthel and his associates reported in a poster presentation.
Overall, 56% of patients on diclofenac gel developed adverse events, compared with 44% of 264 patients treated with placebo gel, added Dr. Barthel, a rheumatologist in Santa Barbara, Calif.
NSAIDs are known to increase risk for cardiovascular or renal problems in a dose-related fashion, especially in older patients and people with hypertension, diabetes, or cardiovascular disease. Topical formulations may reduce this risk by reducing systemic exposure to NSAIDs compared with oral formulations. The ad hoc analysis compared the gel only to placebo, not to oral therapy, and found higher rates of adverse events for the drug vs. placebo.
Application-site reactions occurred in 8.8% on diclofenac gel and 1.1% on placebo. Serious adverse events occurred in 2.6% on diclofenac and 1.1% on placebo. Adverse cardiovascular events were seen in 2.6% on diclofenac and 1.1% on placebo. Adverse renal events were seen in 1.1% on diclofenac and 0.4% on placebo.
Among more common adverse events, 11% of subjects on diclofenac and 10% on placebo reported headache, 8% on diclofenac and 7% on placebo reported arthralgia, and 8% on diclofenac and 6% on placebo reported back pain.
The analysis included 307 patients with hypertension, 84 with diabetes, and 42 with cardiovascular disease. In the hypertension subgroup, adverse events were seen in 54% of 159 people randomized to diclofenac gel, compared with 45% of 148 people using placebo. In the diabetes subgroup, adverse events occurred in 19 (51%) of 37 patients treated with diclofenac and in 21 (48%) of 47 treated with placebo. In the subgroup with cardiovascular disease, adverse events occurred in 15 (56%) of 27 on diclofenac and in 2 (13%) of 15 on placebo, though none developed an adverse cardiovascular event.
Dr. Barthel conducted the study under a research contract for Novartis, which makes Voltaren. His associates in the study were employees of Novartis or of Endo Pharmaceuticals, which markets the drug.