This post hoc analysis was conducted following long-term treatment of patients with knee osteoarthritis to assess the tolerability of DSG treatment in patient subpopulations with an elevated risk of developing adverse events related to NSAID therapy. Subgroup analyses indicated that DSG was well tolerated in patients ≥ 65 years of age; in patients with comorbid hypertension, type 2 diabetes mellitus, or cerebrovascular or cardiovascular disease; and even in patients with diagnoses of all three comorbidities combined. The frequency of any adverse event was not increased in these subpopulations compared with patients < 65 years of age or patients without these comorbid conditions. However, application site dermatitis was more frequently reported among patients ≥ 65 years of age compared with patients < 65 years of age.
Knee osteoarthritis is a condition that occurs commonly among individuals aged ≥ 65 years25
and frequently requires medical intervention. Therapy for patients with osteoarthritis must balance pain relief and potential treatment-related side effects. This may be particularly challenging in patients who are predisposed to these adverse events, such as the elderly. Although NSAIDs are able to provide analgesia for osteoarthritis, the age-related risks of gastrointestinal,3
adverse events effectively limit the usefulness of this drug class. Cardiovascular disease26
as well as gastrointestinal disorders27
occur at a higher frequency in the elderly. Medications used to treat comorbid conditions in the elderly have the potential to interact with NSAIDs, further increasing the risk of adverse events.28
Topical NSAIDs, such as DSG, can provide local pain relief as effectively as oral NSAIDs,16
presumably with more limited systemic exposure, thus reducing the risk of adverse events.
An earlier analysis of pooled data from patients treated for 12 weeks with DSG indicated that the occurrence of most adverse events was similar in patients ≥ 65 years of age compared with patients < 65 years of age.22
In that analysis, a higher percentage of patients aged ≥ 65 years (8.8%) reported application site dermatitis, compared with patients aged < 65 years (5.6%).22
The percentage of patients experiencing adverse events who had hypertension, type 2 diabetes mellitus, or cerebrovascular or cardiovascular disease was similar compared with patients who did not have these comorbid conditions.22
The post hoc analysis reported here extends the results of that study and indicates that DSG may be safely used over a longer period to treat knee osteoarthritis in patients at higher risk for the development of adverse events.
The overall rate of adverse events was not increased in patients with hypertension, type 2 diabetes mellitus, or cerebrovascular or cardiovascular disease compared with patients without these comorbidities. Likewise, rates of gastrointestinal adverse events and application site dermatitis were not influenced by the presence of the comorbid conditions. The incidence of cardiovascular adverse events was somewhat higher in patients with these comorbidities, but this is not surprising considering the well known associations between hypertension, type 2 diabetes mellitus, and cerebrovascular or cardiovascular disease, and the risk of experiencing an adverse cardiovascular event. Given that the American Heart Association advises caution when using NSAIDs in patients with elevated cardiovascular risk,6
the favorable tolerability of DSG in patients with multiple comorbidities and associated elevated cardiovascular risk is of particular clinical relevance. It is especially important that DSG was well tolerated by the 15 patients with combined diagnoses of all three comorbid conditions. This triad of disorders would include patients with metabolic syndrome (a constellation of cardiovascular risk factors defined by World Health Organization as glucose intolerance, impaired glucose tolerance, and/or type 2 diabetes mellitus plus two of the following: central obesity, raised plasma triglycerides and/or low HDL-cholesterol, raised arterial pressure, insulin resistance, microalbuminuria, or impaired glucose regulation29
). The incidence of metabolic syndrome is increased in patients with osteoarthritis.30
This post hoc analysis was limited by the small sample size of a number of the subgroups, particularly patients with type 2 diabetes mellitus or cerebrovascular or cardiovascular disease and those in the multiple comorbidity group, thus precluding statistical testing of differences in tolerability between subgroups. Also, the protocol of the original study excluded patients with serious or unstable illness; thus, some patients seen in clinical practice with hypertension, type 2 diabetes mellitus, and cerebrovascular or cardiovascular disease may be more ill than those studied in this post hoc analysis. Further studies would be of value that specifically enroll patients with these comorbidities and do not exclude those with more serious illness. The patients in this study were treated for knee osteoarthritis, and the results cannot be extended to patients with osteoarthritis of the hand or other areas. Another limitation is the absence of comparator groups treated with placebo or an oral NSAID. Nevertheless, this study provides clinically relevant data that are important for patients with osteoarthritis of the knee and the physicians who treat them.