Non-acidic NSAIDs in the Treatment of Post-traumatic Persistent Synovitis of the Knee Joint: Safety and Efficacy

Persistent inflammation is a long-term inflammatory process that persists even in the absence of overt clinical symptoms. Such inflammation can occur and persist in a joint with various types of injuries and especially in patients who have concomitant osteoarthritis with an inflammatory phenotype / endotype. The objective: to evaluate the efficacy and safety of nabumetone in the treatment of patients with persistent synovitis (lasting more than 3 weeks) in the setting of acute and degenerative knee meniscal injuries which were treated surgically. Materials and methods. The clinical study was designed as a randomized, prospective, comparative study. Two groups were formed: the main group – MG (n = 30 patients) and the comparison group – CG (n = 30 patients). The average age of the patients was 44.3 ± 2.7 years. There were 41 female patients (68%), 19 male (32%) patients. During the X-ray examination with functional load, signs of early stages of osteoarthritis from 1st to 2nd stages according to the Kellgren–Lawrence classification were determined in both groups. The study included patients with degenerative and acute injuries of the meniscus of the knee joint, which were treated surgically (arthroscopically), in whom persistent long-term synovitis was observed in the postoperative period after a standard course of postoperative drug therapy and rehabilitation, which was determined during clinical and ultrasound examinations within 3 weeks after surgery. In the MG, in order to eliminate inflammation, patients were prescribed nabumetone in a daily dose of 1000 mg (500 mg 2 times a day) for 10 days. Subsequently, in order to assess the effectiveness of treatment and the stability of the clinical effect, patients were prescribed the same nonsteroidal anti-inflammatory drug (NSAID) in a dose of 500 mg 1 time per day only “on demand” for a period of up to 1 month. In the CG, patients were prescribed the classic non-prescription NSAID ibuprofen in a dose of 400 mg 2 times a day for a similar period of time (10 days). Subsequently, similarly to the MG, the patients were prescribed the same NSAID in a dose of 400 mg 1 time per day “on demand” for 1 month. The analysis of efficacy and safety was performed before treatment, in 10 days and 1 month after its start based on the assessment of the following criteria and parameters: pain intensity according to visual analogue scale (VAS), functional status according to the Lisholm scale, periarticular edema according to the Doyle index, average weekly need for NSAIDs after a 10-day course of treatment, assessment of the safety and tolerability of the NSAIDs. Results. After 10 days in both groups a good analgesic effect was found, which was according to VAS 19.4 ± 0.7 vs 22.9 ± 0.4, with no difference between the groups (p = 0.089). In the next 3 weeks, patients in the MG had a stable analgesic effect and no need for nabumetone “on demand”. At the same time, in the CG, on the contrary, a tendency to a gradual increased pain intensity was determined 15.1 ± 0.1 vs 23.7 ± 0.3, the difference between the groups was significant (p = 0.012), and the need for ibuprofen “on demand” was 844.6 ± 15.2 mg per week (≈ 400 mg – 2 times a week). The Lisholm score showed a better functional outcome in the MG both after 10 days: 86.9 ± 0.8 vs 77.1 ± 0.3 (p = 0.029) and after 1 month: 94.8 ± 0.8 vs 78.9 ± 0.3 (p = 0.034). The Doyle index score also showed a statistical difference between the groups both after 10 days: 12.8 ± 0.6 vs 15.1 ± 0.4 (p = 0.048) and after 1 month: 8.6 ± 0.7 vs 16.3 ± 0.4 (p = 0.016). At the same time, patients in the CG continued to use NSAIDs (ibuprofen) in an average weekly dose of 844.6 ± 15.2 mg (at least 400 mg – 2 times a week), while the patients in the MG did not need to take NSAIDs “on demand”. There was no difference in the number of patients with undesirable side effects in the groups: 5 (16%) vs 7 (23%) (p > 0.05). However, in terms of the frequency of individual side effects, it was found that pain and discomfort in the epigastrium, as well as a feeling of nausea, occurred less often in the MG: 6% vs 23% and 6% vs 20% (p < 0.05). Conclusions. An important element of the treatment of patients with post-traumatic persistent synovitis on the background of osteoarthritis with an inflammatory endotype / phenotype is the rational choice of a synovial membrane-tropic, safe anti-inflammatory drug in an adequate dose and an effective course, which may be longer than the standard one. The non-acidic NSAID nabumetone meets these requirements.