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

ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-randomized-multicentre-double-blind-placebo-controlled-trial-of-anti-tnf-alpha-adalimumab-in-refractory-hand-osteoarthritis-the-dora-study/