几十年来用于治疗炎症性关节炎的两种药物也可能对一些手部骨关节炎(OA)患者有益。That’s according to two new studies presented at the 2019 American College of Rheumatology (ACR) annual meeting in early November in Atlanta.
According to the Centers for Disease Control and Prevention, about 40 percent of people will develop hand OA at some point in their lives, but contrary to popular belief that onset comes at an older age, it often starts in mid-life. Stiff, painful fingers can make it hard to engage in the most common activities of daily living, such as typing, using a cellphone, buttoning a shirt or opening a jar.
OAhas long been considered a degenerative disease caused by the degradation of cartilage due to so-called “wear and tear,” not inflammation. Medical treatments include non-narcotic pain relievers (such as acetaminophen and nonsteroidal anti-inflammatories), which may not always be effective and don’t stop the disease from progressing.
Recent evidence shows that at least some people with OA also have inflammation, including in the joint lining (synovitis). So researchers started looking to see if drugs used for inflammatory arthritis might work for OA, too.
Until now, the results have generally been disappointing. A 2018 analysis of 11 randomized controlled trials of different drugs commonly used to treat rheumatoid arthritis (RA) found they were no better than placebo for OA symptoms. But the two new studies presented at the conference had different results.
Study 1: Corticosteroids
In this study, patients with signs of synovitis were randomized to receive either a six-week course of 10 mg daily of thecorticosteroid prednisoloneor a placebo. At the end of the trial, the corticosteroid group’s finger pain decreased significantly compared to the placebo group’s (by an average of 21 points vs. 5 points, respectively, measured using the visual analog scale (VAS). The prednisolone group also fared better on other measures, including decreased inflammation as seen on imaging tests. The problem is that long-term corticosteroid use can cause a host of serious side effects, including osteoporosis, glaucoma and diabetes.
The study’s lead author, Féline Kroon, is a PhD student at Leiden University Medical Center in the Netherlands. She explains that symptoms of hand OA can fluctuate over time, with periods of increased pain and swelling. Her group wanted to see if prednisolone, a powerful anti-inflammatory, would be effective in controlling pain during flares. It’s not intended for long-term use, she says, noting that “in light of the risk of complications, prescription of prednisolone for prolonged periods of time in patients with hand osteoarthritis should be discouraged.”
Still, she says the results of the study show that corticosteroids may be an effective short-term treatment option when nothing else works. Short-term also describes the durability of the benefits: the patients’ pain returned when they were weaned off the drug.
David Pisetsky, MD, a rheumatologist at Duke University School of Medicine in Durham, North Carolina, who was not involved in the study, is somewhat ambivalent about the results.
“They’re important because they suggest that some patients with OA can be treated with prednisolone or prednisone,” he says. “But given the side effects, many more studies are needed to determine the patients who would benefit from such an approach, the dose and duration of therapy, and the potential side effects in this patient population.”
Study 2: Methotrexate
In the second study, French researchers followed patients with erosive hand OA for a year. Erosive OA mainly affects older women and causes severe flares and bone loss. One group in the study received a weekly dose of 10 mg ofmethotrexate是治疗类风湿性关节炎最常用的处方药。另一组则服用安慰剂。我们的期望是甲氨蝶呤可以通过控制炎症来缓解疼痛和减缓关节损伤，就像它在类风湿性关节炎中的作用一样。
As it turned out, the drug didn’t control pain any better than placebo. But it did slow joint erosion and even led to some bone healing (remodeling).
Lead study author Christian Roux, MD, head of the joint unit in the rheumatology department at Cote D’Azur University, says the lack of pain relief is probably due to the “multifactorial origin of pain in hand osteoarthritis – that is, it’s caused by both inflammation and mechanical damage – unlike RA, where pain is due to inflammation only.”
他还说，如果患者在损伤发生之前及早治疗，甲氨蝶呤可能会更有效地控制疼痛。他解释说:“如果治疗太晚，疼痛的机械来源可能会成为主要原因，因此甲氨蝶呤将不会有效。”“需要一项关于早期治疗的新研究来帮助证明这一点。”
He says many more studies on the use of methotrexate for hand OA are needed overall. Still, Dr. Roux says it may offer hope for a disease with no real treatment.
Dr. Pisetsky says it makes sense to try proven therapies like methotrexate for inflammatory forms of OA. But he points out that the lack of effectiveness for pain are consistent with what doctors have seen with their own patients. —琳达RATH
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