For Osteoarthritis, NSAIDs Linked to Negative Clinical Outcomes and Higher Costs

Clinical Pain Medicine


NOVEMBER 12, 2020

For Osteoarthritis, NSAIDs Linked to Negative Clinical Outcomes and Higher Costs

Patients with osteoarthritis of the hip and/or knee who were prescribed oral nonsteroidal anti-inflammatory drugs (NSAIDs) experienced an increase in negative clinical outcomes and costs, according to a retrospective study presented at the recent 2020 PAINWeek Virtual Conference.

“It is important to understand the benefits and harms of a standard therapy for osteoarthritis that is recommended in both national and international guidelines,” said principal investigator Stuart Silverman, MD, a clinical professor of medicine and rheumatology at Cedars-Sinai Medical Center, in Los Angeles.

Silverman noted that most clinicians are aware of the increase in gastrointestinal (GI) side effects with the NSAID class, but may be less aware of potential cardiovascular and renal effects.

The study, which is among the first to provide estimates of both the substantial clinical and economic burden of patients with osteoarthritis who have initiated oral NSAID therapy, identified patients from the administrative claims records of Optum Healthcare Solutions, a database containing health care and prescription drug utilization records for approximately 19 million privately insured lives from nearly 100 self-insured companies in the United States.

Adult patient records spanned January 2012 to March 2017, with inclusion criteria for at least two diagnoses of hip and/or knee osteoarthritis and at least a 90-day supply of oral NSAIDs, including COX-2 inhibitors, during the three-year period from first prescription after a patient’s first osteoarthritis diagnosis.

Negative clinical outcomes after initiation of an oral NSAID that were associated with GI conditions increased by 393%, driven by a 667% increase in acute GI hemorrhage. Iron deficiency anemia also increased by 400%.

Furthermore, negative clinical outcomes linked to cardiovascular events increased by 74%, largely due to a 600% increase in acute myocardial infarction. Hypertension increased by 74%.

Lastly, negative clinical outcomes related to renal toxicity increased by 433%, with a 740% increase in acute renal failure being the most prominent.

From the baseline period to follow-up period, the number of patients with at least one inpatient or emergency department visit increased by 293% and 236%, respectively.

All-cause total health care costs increased by 32% (from $32,682 to $43,024), with prescription costs rising by 205% (from $3,306 to $10,093) and hospitalization costs by 21% ($12,330 to $14,916).

In addition, all-cause inpatient admissions increased 293% (from 13.7% to 53.9%) and emergency department visits increased 236% (from 14.8% to 49.7%).

“We need closer monitoring of our patients whom we start on NSAIDs,” said Silverman, who maintains a private rheumatology practice in Beverly Hills. “We need to be aware that GI events in our older patients may be clinically silent. We also need to monitor blood pressures and renal function in our patients that we place on NSAIDs.”

More studies are required to better identify risk factors associated with these negative clinical outcomes, according to Silverman. “The negative outcomes suggest that we need better clinical alternatives to NSAIDs in our management of osteoarthritis patients, particularly the elderly and those at risk of GI, cardiovascular and renal events.”

One of the study authors, Rebecca Robinson, a senior research advisor for Eli Lilly, acknowledged the need for alternatives to NSAIDs, particularly in older individuals in whom GI events, such as peptic ulcer, are silent and in individuals with a risk for GI or cardiovascular conditions.

Joseph V. Pergolizzi Jr., MD, who is the chief operating officer of drug developer NEMA Research, in Naples, Fla., was not surprised by the study results because “long-term use and high doses of these agents are associated with potentially higher rates of side effects.”

Pergolizzi, a Pain Medicine News editorial advisory board member who is not one of the study authors, noted that viable options are needed for these patients. “Currently, there is no ideal analgesic,” he said. “But new modalities are being developed that might enhance analgesia and improve tolerance.”

To better define and understand the true utility of treatment regimens, he said, long-term analgesic safety trials and creating improved patient-reported outcome measurement tools are required.

—Bob Kronemyer

Daniel Nelson MD

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