AT OARSI 2015
SEATTLE (FRONTLINE MEDICAL NEWS) – Hydroxychloroquine is not efficacious for treating primary hand osteoarthritis, according to results from the first randomized trial to test the disease-modifying antirheumatic drug in this patient population.
Findings reported at the World Congress on Osteoarthritis showed that after 24 weeks of treatment, scores for pain and hand function budged little from baseline whether patients took hydroxychloroquine (Plaquenil) or a placebo. And although the drug was generally well tolerated, patients in that group more commonly had allergic reactions and developed rashes.
“The results of our study do not support the prescription of hydroxychloroquine in patients with hand osteoarthritis,” concluded lead investigator WeiChing Lee, Pharm.D., hospital pharmacist at the Maasstad Hospital Rotterdam in the Netherlands.
During a question and answer period, however, session attendees pointed out some study limitations that may still leave the door open for hydroxychloroquine in this setting.
“Thank you for doing this trial. I’ve always wanted to see a randomized, controlled trial looking at this. I’m a little depressed that it’s negative,” commented session attendee Dr. Grace Lo of the Baylor College of Medicine in Houston. An older case series did suggest a benefit of hydroxychloroquine in patients with more severe disease, “so I was wondering why you specifically excluded those people from this study.”
“We believed that patients with very severe disease are not likely to benefit from hydroxychloroquine because it is in the end stage,” Dr. Lee replied.
Dr. Lo further wondered if outcomes had been assessed separately among patients with different anatomic types of hand osteoarthritis, such as carpometacarpal osteoarthritis versus osteoarthritis of the proximal and distal interphalangeal joints. The investigators have not performed those analyses, according to Dr. Lee. “You just need to see if there is a difference,” Dr. Lo recommended.
Another attendee noted that pain scores at baseline suggested some patients had little to no pain. “Did you do a subgroup analysis looking at higher pain scores at baseline versus lower pain scores?” he asked.
“Yes, we did a subanalysis of patients with a pain score of 60 mm or more versus less [on a 100-mm scale], and we saw it improved with more severe pain symptoms; there was a decrease of 15 mm in the pain scores in both the placebo and hydroxychloroquine groups,” Dr. Lee replied, and still no difference between groups.
“Were you surprised there was no placebo response?” that attendee further asked.
“Yes, we were. That was the reason why we did the subanalysis,” Dr. Lee said; results showed a placebo effect in the group with more severe pain but not in the group with less severe pain.
A third attendee asked, “Do you have any data on how much inflammation these patients actually had at baseline? Could the lack of effect be due to low inflammation at baseline?”
The investigators have not looked at inflammatory markers, Dr. Lee replied.
In an interview, Dr. Xavier Chevalier, session comoderator and head of the department of rheumatology at the Henri Mondor Hospital, University Paris XII, in Créteil, France, agreed with the attendees’ points. “Unfortunately, this is a negative trial, but I’m afraid that the level of pain was not really well defined at the beginning of the study,” he said. “And it’s a little bit of a shame that they didn’t include patients with a very high level of pain.”
Introducing the study, Dr. Lee noted, “The cause and pathophysiology of hand osteoarthritis have not been clarified yet, but it is clear that inflammation plays an important tole. So it is believed that anti-inflammatory drugs might be effective in treating hand osteoarthritis.”
“Hydroxychloroquine is an anti-inflammatory drug that has been used successfully in other rheumatic diseases. It is prescribed commonly in hand osteoarthritis, but this indication is off label and not well investigated,” she said.
The investigators recruited to the trial 202 patients who met American College of Rheumatology criteria for primary hand osteoarthritis from outpatient rheumatology clinics in the Netherlands.
The patients had had pain from their arthritis for at least 1 year and had nodules or Kellgren-Lawrence grade 1, 2, or 3 changes in at least two symptomatic joints; those with grade 4 changes were excluded. They were randomized evenly to treatment with hydroxychloroquine (400 mg daily) or placebo.
Pain at baseline averaged about 44 mm on the 100-mm Visual Analog Scale (VAS) pain scale in each group, according to data reported at the meeting sponsored by the Osteoarthritis Research Society International.
Intention-to-treat analyses showed that at 24 weeks, the VAS score had increased by 0.10 mm in the placebo group and decreased by 1.3 mm in the hydroxychloroquine group, but the difference was not significant, reported Dr. Lee, who disclosed that she had no relevant conflicts of interest.
The groups were likewise statistically indistinguishable with respect to the change from baseline in the Australian/Canadian Osteoarthritis Hand Index (AUSCAN) scores and in total scores on the short form of the Arthritis Impact Measurement Scales 2 (AIMS2-SF).
About a fifth of patients in each group experienced adverse events. The hydroxychloroquine group had more allergic reactions (three vs. none) and cases of rash/pruritus (eight vs. three).
Dr. Lee disclosed that she had no relevant conflicts of interest.