Having full mobility is considered one of the prerequisites of a healthy and happy life. Everyday tasks can become much more difficult, if not impossible, if your mobility is severely restricted and pain in your back can be a major problem for this. Back pain is an affliction that most people will experience at some time during their life and it can be caused by a number of factors, most of which can be managed with some care and attention.

A common factor causing this debilitating condition for older people can be osteoporosis, which weakens the bones making them more at risk of fracturing and also affecting posture. Both of these can lead to pain in your back, which tends to be a fairly common complaint for osteoporosis sufferers. Aging itself can be a contributory factor to back pain as muscles weaken and good posture is lost. Younger people can also experience back pain, however and it is not just confined to the older members of the population.

Many people these days work on computers and sitting in a poorly aligned chair for hours on end can affect your back. Poor posture and slouching can strain the muscles in your back and this in turn can put pressure on the vertebrae leading to back pain. Other factors which may contribute to back pain include obesity, with the extra weight being carried putting stress on your back. Poor lifestyle choices such as lack of exercise may also have an impact, as it can lead to weakened muscles and back pain. The key to successfully treating back pain is understanding the factors which caused it.

Once this is established common therapies which are recommended include chiropractic and physical therapy, massage and even acupuncture which has been shown to help. Gentle exercise which can strengthen back muscles may be recommended and this can include light swimming and walking. For more severe cases medication may be prescribed, but this tends to mask the back aching rather than curing it and so should be used sparingly.

• Explain to patients that two investigational pain relievers caused less gastrointestinal ulceration compared with conventional pain relievers.
• Explain that neither drug is currently available.
• Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered preliminary until published in a peer-reviewed journal.

SAN DIEGO — Two investigational pain relievers demonstrated superior gastroprotection when compared with a conventional nonsteroidal anti-inflammatory drug (NSAID) in clinical trials reported here.

A fixed-dose combination of naproxen and the proton pump inhibitor (PPI) esomeprazole reduced the incidence of gastric ulcers by as much as 82% compared with enteric-coated naproxen during six months of treatment. The combination drug significantly reduced the frequency and severity of dyspepsia as assessed by two different standardized scales.

“PN 400 [Vimovo] significantly reduced the incidence of NSAID-associated gastric ulcers in at-risk patients,” Jay Goldstein, MD, of the University of Illinois in Chicago, said at the American College of Gastroenterology meeting.

“This fixed-dose combination drug was associated with fewer upper gastrointestinal symptoms and improved upper GI tolerability,” he added. “Our data suggest that optimizing adherence to gastroprotection may improve NSAID tolerability and may result in sustained use.”

The fixed-dose combination consists of 20 mg of immediate-release esomeprazole and 500 mg of enteric-coated naproxen. The drug design leads to sequential delivery of the two drugs, said Goldstein.

PN 400 was compared with enteric-coated naproxen in two Phase III clinical trials involving patients at risk of ulcers from chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs). The two trials included 434 and 420 patients, who were randomized to BID treatment with PN 400 or enteric-coated naproxen.

Eligible patients had osteoarthritis, rheumatoid arthritis, or another condition requiring chronic NSAID therapy. They were free of ulcers (gastric and duodenal) at baseline. Enrollment included patients ages 50 and older with no history of ulcer and patients ages 18 to 49 who had a history of gastric or duodenal ulcer within the previous five years.

The primary endpoint of both trials was the cumulative incidence of endoscopically proven gastric ulcers at six months. Secondary endpoints included patient-reported outcomes on the Severity of Dyspepsia Assessment (SODA) and Overall Treatment Evaluation of Dyspepsia (OTE-DP).

After six months, the incidence of gastric ulcers in the two trials was 23.1% and 24.3% with enteric-coated naproxen compared with 4.1% and 7.1% for the fixed-dose combination. The differences translated into reductions in ulcer incidence of 82% and 71% with the combination therapy (P<0.001 for both comparisons).

Patient-reported outcomes showed significant advantages for PN 400 with respect to pain intensity, nonpain symptoms, and overall improvement and satisfaction with therapy (P=0.017 to P<0.001).

Rates of adverse events were similar between treatment groups in both trials. The most common adverse events (erosive gastritis, erosive duodenitis, gastritis, and dyspepsia) all occurred less frequently with PN 400. Withdrawal due to adverse events occurred less often with PN 400 (14 and 24 versus 24 and 30 in the two trials).

In response to a question from the audience, Goldstein acknowledged that use of nonprescription formulations of naproxen and a PPI would cost less, but he said adherence and persistence with therapy could be more problematic.

In a separate presentation at the ACG meeting, Goldstein described a cyclooxygenase (COX)-inactive prodrug of naproxen that demonstrated pharmacokinetic equivalence to naproxen with significantly less gastric ulceration in a one-week randomized trial.

He said the prodrug, LT-NS001, reflects an approach to gastroprotection that combines three common strategies: preventing inhibition of COX-1, enteric coating, and acid suppression.

“As a prodrug of naproxen, LT-NS001 has no COX-1 inhibition, minimal COX-2 inhibition, and is readily metabolized to naproxen after systemic absorption,” he said.

“Animal studies suggest the agent is associated with less upper GI mucosal injury.”

Goldstein reported findings from a Phase I-II proof-of-concept study involving 120 healthy volunteers, who received randomized, blinded therapy for 7.5 days in the form of 1200 mg of LT-NS001 or 500 mg of naproxen, each drug administered once daily. The doses chosen represented pharmacokinetic equivalence between the drugs, he said.

The primary efficacy endpoint was the day seven modified Lanza score of upper gastrointestinal mucosal injury. The Lanza scoring system ranges from 0 (no visible lesions) to 7 (ulcer >3 mm in diameter with unequivocal depth).

Mucosal injury was assessed by endoscopy at baseline and day seven, and the Lanza score was determined for gastric and duodenal injury, as well as combined gastroduodenal injury. Baseline Lanza score averaged about 1.0 in both groups.

Endoscopic findings at the end of the study resulted in a mean combined Lanza score 3.5 for naproxen and 2.8 for LT-NS001 (P=0.031). Study participants who received the investigational agent also had fewer gastric ulcers (P=0.020), fewer Lanza scores ≥5 (P=0.012), lower total gastric Lanza score (P=0.005), and fewer gastroduodenal ulcers (P=0.020).

“In this first human proof-of-concept study, the prodrug LT-NS001 was associated with less gastroduodenal mucosal injury than naproxen when dosed to provide equivalent exposure,” Goldstein concluded. “These findings need to be validated further in endoscopic trials of longer duration.”