Predictors for patient satisfaction of a single intra-articular injection of crosslinked hyaluronic acid combined with mannitol (HANOX-M-XL) in patients with temporomandibular joint osteoarthritis. Results of a prospective open-label pilot study (HAPPYMINI-ARTEMIS trial)

Background Chronic pain and functional impairment interfere with the quality of life of subjects suffering from temporomandibular joint (TMJ) disorders. Intra-articular (IA) hyaluronic acid (HA) injections have been shown to alleviate pain and improve mandibular mobility in patients with TMJ osteoarthritis (OA). Objectives The primary aim of the study was to identify the prognostic factors of patient satisfaction for a single IA injection of a mannitol-modified crosslinked HA (HANOX-M-XL) in patients with TMJ-OA. The second goal was to obtain clinical data on effectiveness, safety and mandibular mobility throughout a six-month follow-up period. Patients and methods This was an observational single-arm prospective trial with a six-month follow-up. Inclusion criteria: patients with TMJ-OA which is not relieved by analgesics and/or non-steroidal-anti-inflammatory drugs and/or orthotics, with radiological evidence of TMJ-OA. All patients received a single IA injection of 1 ml HANOX-M-XL in the target TMJ. The primary endpoint was patient satisfaction on day 180. The main secondary outcome measures were pain variation on a 11-point numeric scale (0-11) between the date of injection and month six, the variation over time of the Maximum Inter-Incisal Opening Distance (MIIOD) and the patient's assessment of effectiveness. Predictive factors of success or failure were also studied. All adverse events were recorded. Results 36 subjects (mean age 55.3 years, mean disease duration 98 months), covering a total of 52 injected TMJs, were included. Between baseline and endpoint, the average pain while chewing decreased dramatically from 6.9 +/- 1.2 to 2.9 +/- 1.3 (p < 0.0001) and the MIIOD increased from 29 +/- 7 to 35 +/- 5 mm (p < 0.01). On day 180, all patients were satisfied with the treatment, with 34 patients (94%) rating it as highly effective or effective. Tolerability was good in all but one patient. In the multivariate analysis, patient satisfaction on day 180 was highly correlated with the pain while chewing score, pain on palpation score and the decrease of pain over time (all p < 0.0001) but not with MIIOD, gender, age, bruxism, articular noise and symptom duration. Previous viscosupplementation was also related to higher satisfaction (p = 0.01). Conclusion Despite a long history of pain, most of the patients with symptomatic TMJ-OA benefited from a single injection of HANOX-M-XL, as shown by the sustained (up to 6 months) decrease in pain and improvement in mandibular mobility, with no safety concerns.