DIACEREIN AS THE DRUG OF CHOICE IN THE THERAPY OF KNEE OSTEOARTHRITIS WITH SECONDARY RECURRENT SYNOVITIS

Objective: to evaluate the efficacy and tolerability of diacerein in the therapy of primary knee osteoarthritis (OA) with secondary recurrent synovitis.

Subjects and methods. The 3-month open-label randomized controlled trial enrolled 133 patients with OA. Group 1 consisted of 68 subjects (42 women and 26 men; mean age 54.22±4.29 years) who took diacerein 100 mg/day for 3 months. Group 2 (a control group) included 65 subjects (45 women and 20 men; mean age 53.50±3.27 years) who received chondroitin sulfate 1000 mg/day + glucosamine sulfate 1000 mg/day and meloxicam 7.5 mg/day for 3 months too.

Results and discussion. After a therapy cycle, Group 1 patients displayed a statistically significant decrease in the Lequesne index from 13.92±2.16 to 5.95±0.92 (p=0.00005); in Group 2, this index significantly reduced from 16.72±1.78 to 10.76±1.54 (p=0.001). Pain intensity on the visual analogue scale decreased significantly from 70.88±7.06 to 22.05±6.36 mm (p<0.00001) in Group 1 and from 72.46±7.02 to 39.84±6.67 mm (p<0.0004) in Group 2. A persistent analgesic effect was achieved at weeks 6 and 7 in Groups 1 and 2, respectively. The therapeutic effect was estimated as very good and good by 48 and 52% of the patients, respectively, in Group 1 and as good and moderate by 43 and 57% in Group 2. Three months after a therapy cycle effusion in the affected knee substantially increased (from 21.70±6.29 to 29.16±3.63 ml; p<0.001) in Group 2 and slightly increased (from 5.86±3.10 to 6.12±1.09 ml; p>0.05) in Group 1, which confirms the steady-state effect of diacerein. The results of the performed open-label randomized clinical trial showed marked analgesic and anti-inflammatory effect of diacerein and allow to recommend it as the drug of choice to treat knee OA with secondary recurrent synovitis.

1. Brandt KD, Doherty M, Lohmander LS, editors. Osteoarthritis. Oxford: Oxford University Press; 1998. Vol. 13. Р. 22.

2. Hill CL, Hunter DJ, Niu J, et al. Changes in synovitis are associated with changes in pain in knee osteoarthritis. Digest for ours. Osteoarthritis. 2006;(1):3.

3. Цурко ВВ. Остеоартроз: гериатрическая проблема. Русский медицинский журнал. 2005;13(24):1627–31 [Tsurko VV. Osteoarthritis: geriatric problem. Russkii meditsinskii zhurnal. 2005;13(24):1627–31 (In Russ.)].

4. Benito MJ. Sinovial tissue inflammation in early and late osteoarthritis. Ann Rheum Dis. 2005;64(9):1263–7. doi: 10.1136/ard.2004.025270

5. Маколкин ВИ. Остеоартроз коленного сустава. Терапевтический архив. 2005;77(5):83–6 [Makolkin VI. Osteoarthritis of the knee. Terapevticheskii arkhiv. 2005;77(5):83–6 (In Russ.)].

6. Haywood L, McWilliams DF. Inflammation and angiogenesis in osteoarthritis. Arthritis Rheum. 2003;48:2173–7. doi: 10.1002/art.11094

7. Раскина ТА, Летаева МВ. Новый взгляд на проблему терапии остеоартроза. Современная ревматология. 2012;6(4):86–9 [Raskina TA, Letaeva MV. A new view of the therapy of osteoarthrosis. Sovremennaya Revmatologiya = ModernRheumatology Journal. 2012;6(4):86–9 (In Russ.)].

8. Петров АВ, Романец ВН. Динамика сонографических изменений синовиальной оболочки коленных суставов у больных остеоартрозом. Украинский ревматологический журнал. 2011;(4):1–4 [Petrov AV, Romanets VN. Dynamics of sonographic changes in the synovial membrane of the knee in patients with osteoarthritis. Ukrainskii revmatologicheskii zhurnal. 2011;(4):1–4 (In Russ.)].

9. Абдуллаев РЯ, Дзяк ГВ, Дудник ТА, Федько АА. Ультрасонография коленного сустава. Учебное пособие. Харьков; 2010. С. 50. [Abdullaev RYa, Dzyak GV, Dudnik TA, Fed'ko AA. Ul'trasonografiya kolennogo sustava. Uchebnoe posobie [Ultrasonography knee. Textbook]. Khar'kov; 2010. P. 50.].

10. Хитров НА. Остеоартроз – болезнь с воспалительными и катаболическими процессами в суставах. Трудный пациент. 2012;10(1):41–5 [Khitrov NA. Osteoarthritis – a disease with inflammatory and catabolic processes in the joints. Trudnyi patsient. 2012;10(1):41–5 (In Russ.)].

11. Балабанова РМ. Роль интерлейкина 1 при остеоартрозе и возможности его блокирования. Современная ревматология. 2011;5(1):58–62 [Balabanova RM. Role of interleukin-1 in osteoarthrosis and possibilities of its arrest. Sovremennaya Revmatologiya = ModernRheumatology Journal. 2011;5(1):58–62 (In Russ.)].

12. Mastbergen SC, Bijlsman JW, Lafeber FP. Synthesis and release of human cartilage matrix proteoglicans are differently regulated by nitric oxide and prostaglandin E2. Ann Rheum Dis. 2008;67:52–8. doi: 10.1136/ard.2006.065946

13. Ren K, Torres R. Role of IL-1 beta during pain and inflammation. Brain Res Rev. 2009;60:57–64. doi: 10.1016/j.brainresrev. 2008.12.020

14. Mendes A, Caramona MM, de Carvalho AP, et al. Diacerhein and Rhein reduce the ICE-induced IL-1b-induced nuclear factorkappa B activation by inhibiting the degradation of inhibitor kappa B-alfa. Pharmacol Toxicol. 2002;91:22–8. doi: 10.1034/j.1600-0773.2002.910104.x

15. Балабанова РМ. Новый подход к лечению остеоартроза как хронического воспалительного заболевания. Современная ревматология. 2013;7(2):95–8 [Balabanova RM. A novel approach to treating osteoarthrosis as a chronic inflammatory disease. Sovremennaya Revmatologiya = ModernRheumatology Journal. 2013;7(2):95–8 (In Russ.)].

16. Балабанова РМ. Роль иммунного воспаления в патогенезе остеоартроза, возможности коррекции иммунных нарушений. Современная ревматология. 2011;5(4):74–8 [Balabanova RM. Role of immune inflammation in the pathogenesis of osteoarthrosis and possibilities of correction of immune impairments. Sovremennaya Revmatologiya = Modern Rheumatology Journal. 2011;5(4):74–8 (In Russ.)].

17. Дадашева МН. Патогенетические предпосылки терапии дегенеративно-дистрофических заболеваний. Эффективная фармакотерапия. Неврология и Психиатрия. 2013;(1):22–4 [Dadasheva MN. Pathogenic background therapy of degenerative diseases. Effektivnaya farmakoterapiya. Nevrologiya i Psikhiatriya. 2013;(1):22–4 (In Russ.)].

18. Заигрова НК. Оценка эффективности препарата Артрокер® при остеоартрозе коленных суставов. Современная ревматология. 2013;7(4):23–5 [Zaigrova NK. Evaluation of the efficacy of Arthrocare® for knee osteoarthrosis. Sovremennaya Revmatologiya = Modern Rheumatology Journal. 2013;7(4):23–5 (In Russ.)]. doi: 10.14412/1996-7012-2013-2434

19. Kellgren JH, Lawrence JS. Radiografhic assessment of osteoarthritis. Ann Rheum Dis. 1957;16(4):494–501. doi: 10.1136/ard.16.4.494

20. Altman RD, Hochberg MC, Brandt KD, et al. Guidelines for the medical management of osteoarthritis. Part II. Osteoarthritis of the knee. American College of Rheumatology. Arthritis Rheum. 1995;38:1541–6.

21. Нуднов НВ, Николаева МВ. Ультразвуковые признаки воспалительного процесса в различных отделах коленного сустава. Вестник Российского научного центра рентгенорадиологии Минздрава России. 2013;13(1):6 [Nudnov NV, Nikolaeva MV. Ultrasonic signs of inflammation in various parts of the knee joint. Vestnik Rossiiskogo nauchnogo tsentra rentgenoradiologii Minzdrava Rossii. 2013;13(1):6 (In Russ.)].

22. Lang TA, Secic M, editors. How to report statistics in medicine. Annotated guidelines for authors, editors, and reviewers, 2nd ed. Philadelphia: American College of Physicians; 2006.

23. Каратеев АЕ. Достоинства и недостатки диацереина. Современная ревматология. 2014;8(4):90–5 [Karateev AE. Diacerein: Advantages and disadvantages. Modern Rheumatology Journal. 2014;8(4):90–5 (In Russ.)]. doi: 10.14412/2074-2711-2014-4-90-95

24. PRAC recommends suspension of diacerein containing medicines. Committee cites concerns over gastro-intestinal side effects and liver toxicity. 6 December 2013 EMA/679264/2013/rev.2.

25. Fidelix TSA, Macedo CR, Maxwell LJ, et al. Diacerein for osteoarthritis. Cochrane Database of Systematic Reviews. 2014;(2):CD 005117. doi: 10.1002/14651858.CD 005117. pub3.

26. Panova E, Jones G. Benefit-risk assessment of diacerein in the treatment of osteoarthritis. Drug Safety. 2015;38(3):245–52. doi: 10.1007/s40264-015-0266-z