Evaluation of the efficiency and safety of combined therapy with a symptomatic sustained-release drug and hyaluronic acid versus monotherapy with hyaluronic acid in patients with knee osteoarthritis

Osteoarthritis (OA) is the most common joint disease. Searching for new treatment methods and regimens for OA is relevant.Objective: to evaluate the efficiency and safety of therapy with a symptomatic sustained-release drug (Alflutop) in combination with intra-articular hyaluronic acid (HA) injection versus monotherapy with HA in patients with knee OA in routine clinical practice.Patients and methods. A post-registration open-labeled prospective comparative randomized study was conducted to assess the results of treatment in 76 patients (31 men and 45 women; mean age, 49.3±8.5 years; body mass index, 28.4±0.8 kg/m2 ) in two clinical centers in Yekaterinburg and Perm. The patients were randomized into two equal groups, were homogeneous in terms of gender, the frequency of comorbidities, and vital signs (blood pressure, heart rate, and respiratory rate).Group 1 patients received Alflutop as 1-ml daily intramuscular injections (a total of 20 injections) + 2 ml of 1% intraarticular (IA) HA solution injections three times at 1-week intervals; Group 2 patients were given 2 ml of 1% intraarticular HA solution injections three times at 1-week intervals. As an additional therapy, the use of meloxicam 7.5–15 mg/day was permitted, and, if non-steroidal anti-inflammatory drugs were contraindicated, paracetamol 1–3 g/day might be used.Results and discussion. During treatment, both groups of patients showed improvement (compared to the baseline levels). At the same time, evaluating the intergroup values revealed clear differences: a more pronounced decrease in all WOMAC indicators in Group 1 patients: pain scores, 2 [1; 3] vs. 4 [2; 5] in Group 2 (p<0.001); stiffness, 1 [0; 2] vs. 2 [1; 4] (p<0.001); functional insufficiency, 8 [3; 12] vs. 15.5 [12; 20] (p<0.001); and total WOMAC scores, 12 [7; 13] vs. 21.5 [15; 28] (p<0.001). Pain-intensity assessment using the visual analogue scale also showed the more pronounced positive effect of the combination therapy in Group 1 (p<0.001).Alflutop used in combination with HA was shown to be more preferable than HA monotherapy, which was confirmed by the results achieved for all WOMAC indicators. At 6 months, by the last visit, there were pronounced positive changes in all the analyzed parameters in both groups. At the same time, the most significant changes were recorded in the Alflutop + HA group than in the HA group (p<0.001). Perhaps, the mechanism in exhibiting the found synergistic effect of these drugs lies in their different effect on the pathogenesis of the disease. However, further study of this issue is required in multicenter randomized controlled trials.The good safety of the drugs was confirmed: not a single adverse event was revealed.Conclusion. The patients receiving the combination therapy with Alflutop + HA had the best treatment results in all the parameters assessed