Motor cortex stimulation for the treatment of refractory peripheral neuropathic pain.

Epidural motor cortex stimulation (MCS) has been proposed as a treatment for chronic, drug-resistant neuropathic pain of various origins. Regarding pain syndromes due to peripheral nerve lesion, only case series have previously been reported. We present the results of the first randomized controlled trial using chronic MCS in this indication. Sixteen patients were included with pain origin as follows: trigeminal neuralgia (n = 4), brachial plexus lesion (n = 4), neurofibromatosis type-1 (n = 3), upper limb amputation (n = 2), herpes zoster ophthalmicus (n = 1), atypical orofacial pain secondary to dental extraction (n = 1) and traumatic nerve trunk transection in a lower limb (n = 1). A quadripolar lead was implanted, under radiological and electrophysiological guidance, for epidural cortical stimulation. A randomized crossover trial was performed between 1 and 3 months postoperative, during which the stimulator was alternatively switched 'on' and 'off' for 1 month, followed by an open phase during which the stimulator was switched 'on' in all patients. Clinical assessment was performed up to 1 year after implantation and was based on the following evaluations: visual analogue scale (VAS), brief pain inventory, McGill Pain questionnaire, sickness impact profile and medication quantification scale. The crossover trial included 13 patients and showed a reduction of the McGill Pain questionnaire-pain rating index (P = 0.0166, Wilcoxon test) and McGill Pain questionnaire sensory subscore (P = 0.01) when the stimulator was switched 'on' compared to the 'off-stimulation' condition. However, these differences did not persist after adjustment for multiple comparisons. In the 12 patients who completed the open study, the VAS and sickness impact profile scores varied significantly in the follow-up and were reduced at 9-12 months postoperative, compared to the preoperative baseline. At final examination, the mean rate of pain relief on VAS scores was 48% (individual results ranging from 0% to 95%) and MCS efficacy was considered as good or satisfactory in 60% of the patients. Pain relief after 1 year tended to correlate with pain scores at 1 month postoperative, but not with age, pain duration or location, preoperative pain scores or sensory-motor status. Although the results of the crossover trial were slightly negative, which may have been due to carry-over effects from the operative and immediate postoperative phases, observations made during the open trial were in favour of a real efficacy of MCS in peripheral neuropathic pain. Analgesic effects were obtained on the sensory-discriminative rather than on the affective aspect of pain. These results suggest that the indication of MCS might be extended to various types of refractory, chronic peripheral pain beyond trigeminal neuropathic pain.

Lack of efficacy of abatacept in axial spondylarthropathies refractory to tumor-necrosis-factor inhibition.

OBJECTIVE: To assess the efficacy of abatacept in patients with axial spondyloarthropathies who had failed TNFα antagonist therapy. METHODS: Consecutive patients fulfilling criteria for active axial spondyloarthropathy, despite at least two previous TNFα antagonists, were treated with abatacept (10mg/kg) given on days 1, 15, and 29, then every 28 days until week 24. Clinical and laboratory outcome criteria were assessed monthly for 6 months. RESULTS: Seven patients were treated and followed, all women (median age, 39 years; median disease duration, 12 years), five with ankylosing spondylitis and two with undifferentiated spondyloarthropathy. After 6 months of abatacept therapy, no patient had an at least 50% decrease in the BASDAI; a single patient had an at least 2 cm decrease in the BASDAI (-3.8 cm; -49.3%). No significant changes were observed in pain or patient global assessment scores. Inflammatory back pain persisted in all seven patients. When present, enthesitis improved in most patients. Improvements in spinal mobility measures occurred in two patients. There were no clinically significant adverse events. CONCLUSION: A 6-month regimen of abatacept did not meaningfully improve disease activity, function, or other disease parameters in seven patients with axial spondyloarthropathies. These preliminary results do not suggest a strong efficacy of abatacept in axial forms of spondyloarthropathies.

Is IL-6 an appropriate target to treat spondyloarthritis patients refractory to anti-TNF therapy? A multicentre retrospective observational study.

INTRODUCTION: The aim of this study was to evaluate, under real-life conditions, the safety and efficacy of tocilizumab in patients having failed anti-TNFα therapy for spondyloarthritis. METHODS: French rheumatologists and internal-medicine practitioners registered on the Club Rhumatismes et Inflammations website were asked to report on patients given tocilizumab (4 or 8 mg/kg) to treat active disease meeting Assessment of SpondyloArthritis International Society (ASAS) criteria for axial or peripheral spondyloarthritis, after anti-TNFα treatment failure. Safety and efficacy after 3 and 6 months were assessed retrospectively using standardised questionnaires. RESULTS: Data were obtained for 21 patients, 13 with axial spondyloarthritis (46% men; median age, 42 years; disease duration, 11 years; HLA-B27-positive, 92.3%) and eight with peripheral spondyloarthritis (25% men; median age, 40 years; disease duration, 10 years; HLA-B27-positive, 62.5%). No patients with axial disease had at least a 20 mm decrease in the BASDAI, nor a BASDAI50 response or major ASAS-endorsed disease activity score improvements after 3 or 6 months; an ASAS-endorsed disease activity score clinically important improvement was noted at month 3 in five of 13 patients and at month 6 in one of four patients. A good DAS28 response was achieved in four patients with peripheral disease, including one in EULAR remission at month 3. Four patients were still taking tocilizumab at month 6, including one in EULAR remission and one with a good DAS28 response. Tocilizumab was well tolerated, with no serious adverse events. Initially elevated acute-phase reactants declined during tocilizumab therapy. CONCLUSION: In patients having failed anti-TNFα therapy, tocilizumab decreased acute-phase reactants but failed to substantially improve axial spondyloarthritis and was inconsistently effective in peripheral spondyloarthritis.