COURSE OF UVEITIS IN PATIENTS WITH ANKYLOSING SPONDYLITIS

Relapsing uveitis is a serious problem for patients with ankylosing spondylitis (AS). Tumor necrosis factor-α  inhibitors significantly reduce the frequency of uveitis attacks in AS patients, but they are not always available. In this connection, it is appropriate  to evaluate the effect of traditional  disease-modifying antirheumatic drugs on the course of uveitis in AS.

Objective: to compare the frequency of uveitis attacks in AS during combined therapy using sulfasalazine (SULF)  and nonsteroidal  anti-inflammatory drugs (NSAIDs)  versus monotherapy with NSAIDs.

Subjects and methods. A total of 111 patients with significant AS who had at least one uveitis attack during the disease were examined. 49 subjects received combined therapy including SULF 2 grams daily and NSAIDs for at least 1 year. Six of the 49 patients were noted to have frequently relapsing uveitis (above 3 episodes yearly); 43 had no more than 3 ones per year. The remaining 62 patients took NSAIDs only throughout  the follow-up period. Nine of them had an average of 3 uveitis attacks per year; 53 had no more than 3 ones per year. Out of the 49 patients receiving combined therapy with NSAIDs and SULF,  23 took NSAIDs only at least 1 year before SULF use; 10 of them were observed to have frequent relapses in that period and 13 had three or fewer episodes.

Results and discussion. The entire group showed an average of 2.06±2.04 uveitis attacks per year during monotherapy with NSAIDs and 1.41±1.83 attacks yearly during combined therapy with NSAIDs and SULF (p = 0.08). Among the patients with less than 3 uveitis attacks per year, the mean number of episodes was significantly fewer during combined therapy than during NSAID monotherapy: 0.99±0.87 and 1.37±0.91,  respectively (p = 0.04). Among those with frequently relapsing uveitis (more than 3 attacks per year), the mean number of episodes yearly was not significantly different during NSAID monotherapy and combined therapy: 5.7±2.5 and 5.5±2.7,  respectively (p = 0.9). In a subgroup of patients receiving sequentially NSAID monotherapy and combined therapy with NSADs and SULF,  13 patients with three or fewer baseline attacks per year displayed a significant reduction  in the frequency of episodes from 1.92±0.96 to 0.4±0.44 (p = 0.00003). During combined therapy versus monotherapy, 10 patients with frequently relapsing uveitis (over 3 episodes yearly) exhibited an insignificant reduction  in the number of relapses from 5.9±3.02 to 5.33±1.1 (p = 0.6).

Conclusion. Combined therapy with SULF and NSAIDs does not substantially affect the frequency of uveitis episodes in AS patients with frequently relapsing uveitis (above 3 attacks per year), but significantly reduces the number of episodes among patients with its mild course (less than 3 attacks yearly).

1. Годзенко АА, Бочкова АГ, Румянцева ОА и др. Течение и исходы увеита у больных анкилозирующим спондилитом. Научно-практическая ревматология. 2014;52(5):520-6 [Godzenko AA, Bochkova AG, Rumyantseva OA, et al. Progression and outcomes of uveitis in patients with ankylosing spondylitis. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2014;52(5):520-5 (In Russ.)]. doi: 10.14412/1995-4484-2014-520-525

2. Rudwaleit M, Rodevand E, Holck P. Adalimumab effectively reduces the rate of anterior uveitis flares in patients with active ankylosing spondylitis: results of a prospective open-label study. Ann Rheum Dis. 2009;68(5):696-701. doi: 10.1136/ard.2008.092585

3. Coates L, McGonagle D, Bennett A. Uveitis and tumour necrosis factor blockade in ankylosing spondylitis. Ann Rheum Dis. 2008;67:729-30. doi: 10.1136/ard.2007.077370

4. Guignard S, Gossec L, Salliot C. Efficacy of tumour necrosis factor blockers in reducing uveitis flares in patients with spondylarthropathy: a retrospective study. Ann Rheum Dis. 2006;65:1631-4. doi: 10.1136/ard.2006.052092

5. Годзенко АА, Бочкова АГ, Румянцева ОА и др. Влияние терапии ингибиторами фактора некроза опухоли α на частоту обострений увеита у больных анкилозирующим спондилитом. Научно-практическая ревматология. 2014;52(1):27-30 [Godzenko AA, Bochkova AG, Rumyantseva OA, et al. Impact of the therapy with tumor necrosis factor α inhibitors on the frequency of uveitis exacerbations in patients with ankylosing spondylitis. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2014;52(1):27-30 (In Russ.)]. doi: 10.14412/1995-4484-2014-27-30

6. Насонов ЕЛ, редактор. Ревматология: Клинические рекомендации. 2-е изд. Москва: ГЭОТАР-Медиа; 2010. C. 271-89 [Nasonov EL, editor. Revmatologiya: Klinicheskie rekomendatsii. [Rheumatology: Clinical guidelines]. 2nd ed. Moscow: GEOTAR-Media; 2010. P. 271-89].

7. Braun J, van den Berg R, Baraliakos X, et al. 2010 update of the ASAS/EULAR recommendations for the management of ankylosing spondylitis. Ann Rheum Dis. 2011 Jun;70(6):896-904. doi: 10.1136/ard.2011.151027

8. Benitez-Del-Castillo JM, Garcia-Sanchez J, Iradier T, Banares A. Sulfasalazine in the prevention of anterior uveitis associated with ankylosing spondylitis. Eye (Lond). 2000 Jun;14(Pt 3A):340-3. doi: 10.1038/eye.2000.84

9. Munoz-Fernandez S, Hidalgo V, Fernandez-Melon J. Sulfasalazine reduces the number of flares of acute anterior uveitis over a one-year period. J Rheumatol. 2003;(6):1277.

10. Van der Linden S, Valkenburg H, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis: a proposal to modification of the New York criteria. Arthritis Rheum. 1984;27:361-8. doi: 10.1002/art.1780270401

11. Clegg DO, Reda DJ, Abdellatif M. Comparison of sulfasalazine and placebo for the treatment of axial and peripheral manifestations of the seronegative spondyloarthropathies: a Department of Veterans Affairs cooperative study. Arthritis Rheum. 1999;42:2325-9. doi: 10.1002/1529-0131(199911)42:11<2325::AIDANR10>3.0.CO;2-C

12. Chen J, Liu C. Sulfasalazine for ankylosing spondylitis. Cochrane Database Syst Rev. 2005;(2):CD004800.

13. Nissila M, Lehtinen K, Leirisalo-Repo M, et al. Sulfasalazine in the treatment of ankylosing spondylitis: a twenty-six-week, placebo-controlled clinical trial. Arthritis Rheum. 1988;31:1111-6. doi: 10.1002/art.1780310905

14. Schmidt WA, Wierth S, Milleck D, et al. Sulfasalazine in ankylosing spondylitis: a prospective, randomized, double-blind placebo-controlled study and comparison with other controlled studies. Z Rheumatol. 2002;61(2):159-67. doi: 10.1007/s003930200024

15. Chen J, Liu C. Is sulfasalazine effective in ankylosing spondylitis?A systematic review of randomized controlled trials. J Rheumatol. 2006;33(4):722-31.

16. Braun J, van der Horst-Bruinsma IE, Huang F, et al. Clinical efficacy and safety of etanercept versus sulfasalazine in patients with ankylosing spondylitis: a randomized, double-blind trial. Arthritis Rheum. 2011;63:1543-51. doi: 10.1002/art.30223

17. Ward MM, Kuzis S. Treatments used by patients with ankylosing spondylitis: comparison with the treatment preferences of rheumatologists. J Clin Rheumatol. 1999;(5):1-8. doi: 10.1097/00124743-199902000-00001

18. Ward MM. Sulfasalazine for the treatment of ankylosing spondylitis: Relic or niche medication? Arthritis Rheum. 2011;63(6):1472-4. doi: 10.1002/art.30225

19. Van der Heijde D, Landewe R, van der Linden S. How should treatment effect on spinal radiographic progression in patients with ankylosing spondylitis be measured? Arthritis Rheum. 2005;52:1979-85. doi: 10.1002/art.21133

20. Collantes E, Zarco1 P, Munoz E, et al. Disease pattern of spondyloarthropathies in Spain: description of the first national registry (REGISPONSER) – extended report. Rheumatology. 2007;46:1309-15. doi: 10.1093/rheumatology/kem084

21. Эрдес ШФ, Волнухин ЕВ, Галушко ЕА и др. Лечение больных анкилозирующим спондилитом в реальной практике врача-ревматолога в России. Научно-практическая ревматология. 2013;51(1):15-20 [Erdes SF, Volnuhin EV, Galushko EA, et al. Treatment in patients with ankylosing spondylitis in the real clinical practice of a rheumatologist in Russia. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2013;51(1):15-20. (In Russ.)]. doi: 10.14412/1995-4484-2013-1195.