FROM ARTHRITIS RESEARCH & THERAPY
Ultrasound evaluation at the time of clinical remission could be a useful tool to select the most appropriate rheumatoid arthritis (RA) patients to undergo biologic therapy tapering and discontinuation, Italian researchers say.
In a study involving 42 RA patients in clinical remission who tapered their anti–tumor necrosis factor–alpha (anti-TNF-alpha) therapy according to ultrasound criteria, 69.1 % maintained remission at 12 weeks.
Furthermore, 26 of the patients (89.7 %) maintained disease remission after 6 months of follow-up, reported the research team led by Dr. Gianfranco Ferraccioli and Dr. Stefano Alivernini of the Institute of Rheumatology, Catholic University of the Sacred Heart, Rome (Arthritis Res Ther. 2016. doi: 10.1186/s13075-016-0927-z ).
The 30% of patients who relapsed (n = 13) were retreated and reached a good European League Against Rheumatism (EULAR) response within 3 months, results from the observational study showed.
According to the researchers, the daily management of patients receiving long-term biologic treatment remains a matter of debate, and it is currently unclear how to select the most appropriate patients for discontinuing biologic treatment.
People with RA, even when in remission, tend to have residual synovitis. Previous research had shown that patients with negative signaling detected on power Doppler (PD) ultrasound were less likely to have disease flares.
To determine if the detection of residual synovitis with PD signaling could help in selecting patients suitable for anti-TNF discontinuation, the researchers selected 42 RA patients with disease duration of more than 12 months who were in sustained remission (Disease Activity Score less than 1.6 at three visits 3 months apart) who were receiving anti-TNF-alpha treatment plus methotrexate.
Patients were first tapered on anti-TNF-alpha therapy (adalimumab 40 mg/4 weeks or etanercept 50 mg/2 weeks).
Each patient underwent ultrasound evaluation of synovial hypertrophy (SH) and PD signal presence in the second and third metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints, the wrist (radiocarpal-intercarpal), bilateral knee, and second to fifth metatarsophalangeal (MTP) joints.
After 3 months, patients with no power Doppler signaling on ultrasound discontinued anti-TNF-alpha therapy and were followed every 3 months while maintaining stable doses of methotrexate.
Disease flares after anti-TNF-alpha discontinuation occurred in the joints with higher SH scores that were clinically involved at disease onset, despite the fact that no SH cut-off discriminated patients who relapsed from those who did not.
In particular, the fifth MTP joint was informative (in both the tapering and discontinuation groups) and the second MCP joint was informative for the tapering group only.
“This finding suggests the possible utility of following US [ultrasound] with indices of joints initially involved at disease onset with higher likelihood of relapse,” the researchers said.
Results from subgroup of five patients who also underwent ultrasound-guided knee synovial tissue biopsy to assess histologic features of residual synovitis revealed that the absence of ultrasound activity was associated with almost normal findings at the synovial level, they reported.
Overall, the findings suggested there was a “meaningful, large patient population with established RA in remission for whom the anti-TNF-alpha dose can be decreased without clinical and functional worsening,” the researchers wrote.
They suggested the combination of PD-US evaluation and American College of Rheumatology/EULAR remission criteria could help identify patients on biologics who are likely to achieve drug-free remission.
Use of three sequential ultrasound evaluations might identify an even higher proportion of patients likely to reach persistent drug-free remission, compared with current clinical methods of disease activity assessment, they added.
