A multicenter, prospective, randomized trial of the efficacy and safety of Alflutop® in an alternating dosing regimen versus the standard one. Communication 2: Evaluation of the efficacy of the drug in different use regimens

Osteoarthritis (OA) belongs to diseases with high comorbidity and most frequently concurrent with obesity, diabetes mellitus (DM), hypertension, and other cardiovascular diseases (coronary heart disease, atherosclerosis), gastrointestinal tract diseases, and chronic diseases of the lung and kidney. Irrational treatment of OA in the presence of comorbidity and without considering characteristics of drug interactions leads to a pronounced increase in the number of adverse reactions (ARs) and to aggravation of the course of all concomitant diseases. From this point of view, therapy seems to be relevant when the latter involves drugs that have both symptom- and structure-modifying properties and have a high safety profile.

Objective: to compare the safety of alternating and standard treatment regimens with Alflutop® in patients with knee OA.

Patients and methods. 130 patients were enrolled in the trial who had Kellgren-Lawrence Grade II–III primary tibiofemoral knee OA with pain intensity on walking ≥40 mm on a visual analogue scale and who needed to take nonsteroidal anti-inflammatory drugs (≥30 days in the previous 3 months). The patients were randomized into two groups: Group 1 was prescribed Alflutop® 1.0 ml intramuscularly (IM) daily for 20 days (a standard regimen); Group 2 was given 2 ml IM every other day (a total of 10 injections) (an alternating regimen). The duration of follow-up was 14 weeks. The safety of Alflutop® was evaluated by the incidence of ARs and serious ARs (SARs) varying in severity according to medical records, laboratory tests, physical examination, assessment of a patient' vital signs, and electrocardiography (ECG). The patients were examined at the beginning, at the end, and 1 month after therapy.

Results and discussion. No SARs were recorded during the study period and follow-up. There were 10 ARs in the group of patients receiving Alflutop® in the standard regimen and 19 ARs in the other group (the alternating regimen). All ARs corresponded to mild and moderate severity, were unassociated with the test drug, and resolved by the end of the follow-up. 12-lead ECG identified only clinically insignificant abnormalities in the patients of both groups. Patients without DM displayed no clinically significant increase in glucose levels. Those with DM had no increased glycemia tendency. Biochemical studies in both groups revealed only clinically insignificant abnormalities, the frequency of which was insignificant.

Conclusion. This study has confirmed the comparable high safety of Alflutop® in both standard and alternative therapy regimens. It has also shown that the drug has a good safety profile and can be recommended for wide clinical application in any use regimen: 1 ml daily (a total of 20 injections) or 2 ml every other day (a total of 10 injections). 

1. Allen KD, Choong PF, Davis AM, et al. OA: Models for appropriate care across the disease continuum. Best Pract Res Clin Rheumatol. 2016 Jun;30(3):503-35. doi: 10.1016/j.berh.2016.09.003

2. Arden N, Nevit MC. Osteoarthritis: Epidemiology. Best Pract Res Clin Rheumatol. 2006;20(1):3-25. doi: 10.1016/j.berh.2005.09.007

3. Galushko EA. Mediko-sotsial'naya znachimost' revmaticheskikh zabolevanii [The medical and social significance of rheumatic diseases]: Abstract. diss. ... doctor. medical sciences. Moscow; 2011 (In Russ.).

4. Lila AM, Lila VA. Social significance and economic consequences of rheumatic diseases. Gigiena i Sanitariya. 2017;96(4):387-92 (In Russ.).

5. Neogi T, Zhang Y. Epidemiology of OA. Rheum Dis Clin North Am. 2013 Feb;39(1): 1-19. doi: 10.1016/j.rdc.2012.10.004

6. Feinstein AR. Pre-therapeutic classification of co-morbidity in chronic disease. J Chron Dis. 1970;23(7):455-68. doi: 10.1016/ 0021-9681(70)90054-8

7. Kraemer HC. Statistical issues in assessing comorbidity. Stat Med. 1995;14:721-3. doi: 10.1002/sim.4780140803

8. Van den Akker M, Buntinx F, Roos S, Knottnerus JA. Comorbidity or multimorbidity: what is in a name? A review of the literature. Eur J Gen Pract. 1996;2(2):65-70. doi: 10.3109/13814789609162146

9. Boureau F, Schneid H, Zeghari N, et al. The IPSO study: ibuprofen, paracetamol study in osteoarthritis. A randomized comparative clinical study comparing the efficacy and safety of ibuprofen and paracetamol analgesic treatment of osteoarthritis of knee or hip. Ann Rheum Dis. 2004;63:1028-35. doi: 10.1136/ard.2003.011403

10. Bruyere O, Cooper C, Pelletier JP, et al. An algorithm recommendation for the management of knee OA in Europe and internationally: a report from a task force of the European Society for Clinical and Economic Aspects of Osteoporosis and OA (ESCEO). Semin Arthritis Rheum. 2014;44:253-63. doi: 10.1016/j.semarthrit.2014.05.014

11. McAlindon TE, LaValley MP, Gulin JP, Felson DT. Glucosamine and chondroitin for treatment of osteoarthritis: a systematic quality assessment and meta-analysis. JAMA. 2000 Mar 15;283(11):1469-75. doi: 10.1001/jama. 283.11.1469

12. Henrotin Y, Marty M, Mobasheri A. What is the current status of chondroitin sulfate and glucosamine for the treatment of knee osteoarthritis? Maturitas. 2014;78:184-7. doi: 10.1016/j.maturitas.2014.04.015

13. Alekseeva LI, Sharapova EP, Taskina EA, et al. Multicenter double-blind randomized placebo-controlled trial of the symptom- and structure-modifying effect of alflutop in patients with knee osteoarthrosis. Report 1. Evaluation of the symptom-modifying effect of the drug. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2013;51(5):532-8. doi: 10.14412/1995-4484-2013-1545 (In Russ.).

14. Alekseeva LI, Sharapova EP, Taskina EA, et al. A multicenter, blind, randomized, placebo-controlled study of the symptomand structure-modifying effet of alflutop in patients with knee osteoarthritis. Report 2. The assessment of the structure-modifying effect of the drug. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2014;52(2):174-7. doi: 10.14412/1995-4484-2014-174-177 (In Russ.).

15. Alekseeva LI, Taskina EA, Lila AM, et al. A multicenter, prospective, randomized trial of the efficacy and safety of Alflutop® in an alternating dosing regimen versus the standard one. Communication 1: Evaluation of the efficacy of the drug in different treatment regimens. Sovremennaya Revmatologiya = Modern Rheumatology Journal. 2019;13(3): 51-9. doi: 10.14412/1996-7012-2019-3-51-59 (In Russ.).

16. Groppa L, Mynzatu I, Karasava M, et al. The effectiveness of alflutop in patients with deforming arthrosis. Klinicheskaya Revmatologiya. 1995;(3):20-2 (In Russ.).

17. Lukina GV, Sigidin YaA. Experience with the use of the drug alflutop in the treatment of osteoarthrosis. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 1996;34(4):40-3 (In Russ.).

18. Lukina GV, Sigidin YaA. Chondroprotective drug alflutop in the treatment of osteoarthritis. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2001; 39(2):51-3. doi: 10.14412/1995-4484-2001-400 (In Russ.).

19. Korshunov NI, Marasaev VV, Baranova EYa, et al. The role of inflammation and assessment of the chondroprotective effect of Alflutop in patients with osteoarthritis according to magnetic resonance imaging of the knee. Russkii Meditsinskii Zhurnal. 2003; 11(2):13-20 (In Russ.).

20. Chichasova NV, Imametdinova GR, Shevchenko OV. Injection therapy for osteoarthritis. Kachestvo Zhizni. Meditsina. Bolezni Kostno-Myshechnoy Sistemy. 2003; (3):69-72 (In Russ.).

21. Chichasova NV. The place of slowly acting drugs in the rational treatment of deforming osteoarthrosis. Consilium Medicum. 2005; 7(8):634-8 (In Russ.).

22. Svetlova MS, Ignat'eva VK. The use of alflutop in the treatment of patients with osteoarthrosis. Klinicheskaya Meditsina. 2004;(6):52-5 (In Russ.).

23. Drozdov VN, Kolomeets EV. The use of alflutop in patients with osteoarthrosis with gastropathy developed during treatment with NSAIDs. Farmateka. 2005;(20):125-8 (In Russ.).

24. Levin OS, Olyunin DYu, Golubeva LV. Alflutop efficacy in chronic vertebrogenous lumbar ischialgia. A double blind placebo controlled study. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2004;42(4):80-4. doi: 10.14412/1995-4484-2004-809 (In Russ.).

25. Levin OS, Maroseikin TV, Kazakova TV, et al. The effectiveness of alflutop in vertebrogenic cervicobrachialgia. Farmateka. 2008; (6):48-54 (In Russ.).