WASHINGTON – A new study presented this week at the American College of Rheumatology Annual Meeting in Washington D.C., suggests that anti-tumor necrosis factor drugs (also called anti-TNF) offer no relief to patients with chronic pain caused from hand osteoarthritis.

Osteoarthritis, or OA as it is commonly called, is the most common joint disease affecting middle-age and older people. It is characterized by progressive damage to the joint cartilage—the cushioning material at the end of long bones. It can causes changes in the structures around the joint including fluid accumulation, bony overgrowth, and weakness of muscles and tendons, all of which may limit movement and cause pain and swelling.

People with hand osteoarthritis often experience pain in multiple joints and previous studies have documented that the disease does not respond to several of the traditional therapies used in its treatment. However, anti-TNF medications may represent a real hope, because TNF is a molecule found to contribute to the destruction of cartilage and inflammation of joints. Researchers on behalf of the French National Section on OA (led by the Hopital Henri Mondor ) in France recently compared the effectiveness of TNF blockers (commonly called anti-TNFs) and nonsteroidal anti-inflammatory drugs (also called NSAIDs) in controlling pain in people with hand OA.

The digital osteoarthritis in refractory hand OA study (called DORA) included hand OA patients who did not respond to painkillers and NSAIDs. Patients also had to meet the American College of Rheumatology criteria for hand OA with significant pain, at least three painful inter phalangeal hand joints and a minimum of three involved joints identified by X-ray. The study was conducted at 16 different clinical sites. Eighty-five patients were randomly divided into two groups. One group received adalimumab (Humira®), and the other group received placebo. Neither the patients nor the researchers were told who was in which group. Patients were monitored for 26 weeks. Those in the adalimumab group received two injections of the therapy at the beginning and second week of the trial.

Researchers established that a change of more than 50 percent in improvement in pain score after six weeks would be considered therapeutic success. Additional signs of success after six weeks included fewer painful and swollen joints, decreased morning stiffness and improved patient and practitioner assessments. Researchers monitored use of painkillers (acetaminophen up to three grams daily was the only medication allowed until week six) and the progression of the disease using blood and urine tests.

Of the 85 patients (42 in the placebo group, 41 in the adalimumab group), 35 in the placebo group and 38 in the adalimumab group received the two injections. Seventy-eight patients with at least one injection were analyzed (37 placebo and 41 adalimumab). The mean age of the patients was 62.5 years; 85 percent were women. Mean pain level at study beginning was 65.4 millimeters on a zero to 100 mm scale; and patients had a mean of 11 painful joints, and 5.9 clinically inflamed digital joints.

After six weeks of receiving adalimumab and placebo, researchers measured only a 2.5 millimeter difference in the average change in pain score between the groups. At week six, there was no difference between groups on the main outcome – where they measured 50 percent improvement (35.1 percent in the adalimumab group versus 27.3 percent in the placebo group). The only difference recorded was a decrease in the number of swollen joints between week zero and week 26 in the adalimumab group. No other significant changes or concerns were reported.

“Our research found that two injections of anti-TNF failed to improve severe painful hand OA,” says Xavier Chevalier, MD, PhD, head of the department of rheumatology at Hopital Henri Mondor in France and lead investigator of the study. “New trials are needed to find the right target in painful hand OA because this is a disease where we have no real therapy and the patients develop the feeling of a neglected disease.”

Patients should talk to their rheumatologists to determine their best course of treatment.

This study was promoted by the APHP clinical research and osteoarthritis group of the French Society, and funding from Inserm pro A and a grant from ABBOTT laboratory.

The American College of Rheumatology is an international professional medical society that represents more than 9,000 rheumatologists and rheumatology health professionals around the world. Its mission is to advance rheumatology. The ACR/ARHP Annual Meeting is the premier meeting in rheumatology. For more information about the meeting, visit www.acrannualmeeting.org or join the conversation on Twitter by using the official hashtag: #ACR2012.

Editor’s Notes: Xavier Chevalier, MD, PhD, will present this research during the ACR Annual Meeting at the Walter E. Washington Convention Center at 3:45 PM on Tuesday, November 13 in Renaissance Washington - Grand Ballroom North. Dr. Chevalier will be available for media questions and briefing at 8:30 AM on Monday, November 12 in the on-site press conference room, Room 203 A–B.

Presentation Number: 2472

A Randomized, Multicentre, Double Blind, Placebo-Controlled Trial of Anti TNF Alpha (adalimumab) in Refractory Hand Osteoarthritis: The Dora Study

Xavier Chevalier (Department of Rheumatology Hopital Henri Mondor, UPEC Univ ParisXII)

P. Ravaud (Hôpital Hôtel Dieu, Centre d’Epidémiologie Clinique, Paris, France)E. Maheu (Department of Rheumatology, Hopital Saint Antoine University Paris VI, France)G. Baron (Hôpital Hôtel Dieu, Centre d’Epidémiologie Clinique, Paris, France)A. Rialland (Unité de Recherche Clinique, Hopital Henri Mondor, UPEC Paris, France) P. Vergnaud (Laboratoire Synarc, Lyon, France)C. Roux (Department of Rheumatology, Hopital de l’Archet, University Nice, France)Y. Maugars (Department of Rheumatology, University Nantes, France)D. Mulleman. Department of Rheumatology, Hopital Trousseau, University Tours, franceB. Combe (Department of Rheumatology, Hopital Lapeyronnie, University Montpellier, France)D. Wendling (Department of Rheumatology, Centre Hospitalier Universitaire de Besançon, France)P. Laforgue(Department of Rheumatology, Hopital de la Conception, University of Marseille, France)D. Loeuille (Department of Rheumatology, Hopital de la Conception, University of Marseille, France)V. Foltz (Department of Rheumatology, Hopital La Pitié, University Paris VI, France)P. Richette (Hôpital Lariboisière, Fédération de Rhumatologie, Paris, France)

Background/Purpose: Hand osteoarthritis (HOA) is a frequent painful polyarticular disease which often does not respond to any classical therapeutics. TNF a is involved in the osteoarthritic process both in disease progression and in pain perception.

Objective: To evaluate TNF blockers in patients with painful OA refractory to analgesics and NSAIDs. Methods: The digital osteoarthritis in refractory hand OA study (DORA), is a phase 3 randomized superiority, double-blind (patients and assessors of outcomes), parallel, placebo controlled, 26 weeks, multicenter trial (conducted in 16 French clinical sites), using TNF blocker adalimumab (2 sub cutaneous injections at week 0 and week 2). Patients meeting the American College of Rheumatology criteria for hand OA with pain above 40 mm on a 100 mm visual analogue scale (VAS), involving at least 3 painful interphalangeal joints and at least 3 OA joints at Kellgren Lawrence (KL) grade > 2 on a recent radiograph, who did not respond to analgesics and NSAIDs, were recruited. Randomization and allocation to trial group were carried out by a central computer system. The primary endpoint was change in pain score after 6 weeks. Secondary outcomes at 6 weeks were change in the number of spontaneous painful joints, in number of painful joints on pressure, in number of swollen joints, in morning stiffness, in patient’ and practitioner’ global assessments, in functional index for hand OA (FIHOA) and Cochin hand functional index. Consumption of analgesics was recorded (acetaminophen up to 3g/D was the only rescue medication allowed until week 6). Serum markers (COMP, PIIANP, HA, usCRP, cytokines level of TNF a, IL-6, IL-1) and urine level of CTX-II (corrected by creatinine) were measured at W0 and W6

Results: On the 99 patients selected, 85 were randomized (42 in the placebo group, 41 in the adalimumab group). 35 patients in the placebo group and 38 in the adalimumab group received the two injections. 78 patients with at least one injection were analyzed (37 placebo and 41 adalimumab) (mITT). Mean (SD) age was 62.5 (6.9), 85 % of women, mean (SD) level of pain was 65.4 (12.9) mm; mean (SD) number of painful IP joints: 11 (6), mean number of joints with clinical synovitis was 5.9(4.4), mean FIHOA score 15.6 (6.3). The difference in the mean change in pain score on VAS (0-100 mm) over 6 weeks between adalimumab and placebo (primary end point) was: -2.5 mm (95% CI, -14.0 to 9.0), p: 0.67, non significant. No statistically significant differences were found for any of the secondary outcomes, except for a decrease in the number of swollen joints between week 0 and week 26 which favoured adalimumab group: mean difference: -1.9 (95% CI, -3.2 to - 0.6), p: 0.006. Analgesics use was similar between groups. There were no safety concerns. There was none variations of any biological markers between the 2 groups. TNF alpha serum level was not correlated with clinical outcome in the group of patients treated with adalimumab. Conclusion: In a group of patients with refractory hand OA, TNFa blockers (adalimumab, 2 sc injections) failed to demonstrate any clinical improvement. Trial registrationclinicaltrials.gov Identifier: NCT00597623 Academic study sponsored by APHP clinical Research; supported by Osteoarthritis group of the French Society and INSERM Pro A. Grant from Abbot laboratory.

Disclosure: Xavier Chevalier, NoneP. Ravaud, NoneE. Maheu, None G. Baron, None A. Rialland, None P. Vergnaud, NoneC. Roux, NoneY. Maugars, NoneD. Mulleman, None B. Combe, None D. Wendling, NoneP. Laforgue, None D. Loeuille, NoneV. Foltz, NoneP. Richette