Regular use of non-steroidal anti-inflammatory drugs can effectively control pain and global health in patients with moderate activity of rheumatoid arthritis

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used to control pain in rheumatoid arthritis (RA). However, many aspects of the therapeutic effect of NSAIDs in RA have not been sufficiently studied. In particular, this concerns the effect of NSAIDs on the inflammatory activity of the disease.

Objective: to study the comparative efficacy and safety of NSAIDs in RA patients with moderate and low disease activity.

Patients and methods. The study group consisted of 404 patients with RA, 69% women and 31% men, mean age 58.6±10.0 years, with moderate and low disease activity – DAS28<5.1 (mean value 3.7±1.5), who initially had moderate or severe pain: >4 cm on the visual analog scale (VAS) 0–10 cm. All patients received DMARDs, mostly methotrexate 15 to 25 mg weekly, 8.2% biological agents, 18.6% glucocorticoids. All patients were prescribed NSAIDs at the full therapeutic dose. The results of treatment were evaluated after 2 weeks, 1, 3 and 6 months. Criteria of efficacy were the dynamics of pain (10 cm VAS), Patient Global Health (PGH on a 10-cm VAS), the change in the tender joints count (TJC) and swollen joints count(SJC), and dynamics of RA activity (DAS28).

Results and discussion. 54.2% of patients received aceclofenac, 19.8% nimesulide, 14.3% meloxicam, 9.1% diclofenac, 2.6% – other NSAIDs. After 2 weeks, the pain decreased from 6.3±1.2 cm to 4.5±1.5 cm on VAS (p<0.001). The severity of pain continued to decrease further, and after 6 months of observation was 4.0±1.2 (p< 001, compared with the baseline level). A similar result was observed for the TJC, SJC, and PGH: the dynamics of these indicators, in comparison with the baseline level, was statistically significant after 2 weeks and after 1, 3, and 6 months of observation (p< 0.05). There was a decrease in the disease activity by DAS28: from 3.7±1.5 to 3.4±1.1 after 3 months (p=0.041) and 3.1±0.9 after 6 months (p=0.02). The effectiveness of aceclofenac and other NSAIDs for pain reduction, TJC, SJC, PGH and DAS28 did not differ. The tolerability of aceclofenac was better than of other NSAIDs: the frequency of dyspepsia after 2 weeks was 23.3% and 36.2% (p=0.004). The frequency of arterial hypertension and edema in patients who used aceclofenac, after 2 weeks and 6 months was slightly lower than in patients treated with other NSAIDs, but the difference was not statistically significant.

Conclusion. The use of NSAIDs can effectively control the pain and other symptoms of RA, as well as the disease activity by DAS28 in patients with moderate or low disease activity. Aceclofenac is not inferior to other NSAIDs in analgesic potential and exceeds them in tolerability.

1. Nasonov EL, editor. Rossiiskie klinicheskie rekomendatsii. Revmatologiya [Russian clinical guidelines. Rheumatology]. Moscow: GEOTAR-Media; 2017. 464 p.

2. Sparks JA. Rheumatoid Arthritis. Ann Intern Med. 2019 Jan 1;170(1):ITC1-ITC16. doi: 10.7326/AITC201901010.

3. Burmester GR, Pope JE. Novel treatment strategies in rheumatoid arthritis. Lancet. 2017 Jun 10;389(10086):2338-48. doi: 10.1016/S0140-6736(17)31491-5.

4. Lampa J. Pain without inflammation in rheumatic diseases. Best Pract Res Clin Rheumatol. 2019 Jun;33(3):101439. doi: 10.1016/j.berh.2019.101439.

5. Harth M, Nielson WR. Pain and affective distress in arthritis: relationship to immunity and inflammation. Expert Rev Clin Immunol. 2019 May;15(5):541-52. doi: 10.1080/1744666X.2019.1573675. Epub 2019 Feb 11.

6. Vergne-Salle P, Pouplin S, Trouvin A, et al. The burden of pain in rheumatoid arthritis: Impact of disease activity and psychological factors. Eur J Pain. 2020 Nov;24(10): 1979-89. doi: 10.1002/ejp.1651. Epub 2020 Sep 11.

7. Steffen А, Holstiege J, Klimke K, et al. Patterns of the initiation of disease-modifying antirheumatic drugs in incident rheumatoid arthritis: a German perspective based on nationwide ambulatory drug prescription data. Rheumatol Int. 2018 Nov;38(11): 2111-20. doi: 10.1007/s00296-018-4161-7. Epub 2018 Oct 10.

8. Black RJ, Richards B, Lester S, et al. Factors associated with commencing and ceasing opioid therapy in patients with rheumatoid arthritis. Semin Arthritis Rheum. 2019 Dec;49(3):351-7. doi: 10.1016/j.semarthrit.2019.06.003

9. Kimsey L, Weissman JS, Patel A, et al. Delay in initiation of DMARD or antiinflammatory therapy in patients newly diagnosed with rheumatoid arthritis: An analysis of United States Military Health System TRICARE beneficiaries. Semin Arthritis Rheum. 2019 Apr;48(5):821-7. doi: 10.1016/j.semarthrit.2018.07.003.

10. Fidahic M, Jelicic Kadic A, Radic M, Puljak L. Celecoxib for rheumatoid arthritis. Cochrane Database Syst Rev. 2017 Jun 9;6(6):CD012095. doi: 10.1002/14651858.CD012095.pub2.

11. Kvien T, Greenwald M, Peloso P, et al. Do COX-2 inhibitors provide additional pain relief and anti-inflammatory effects in patients with rheumatoid arthritis who are on biological disease-modifying anti-rheumatic drugs and/or corticosteroids? Post-hoc analyses from a randomized clinical trial with etoricoxib. Randomized Controlled Trial. BMC Musculoskelet Disord. 2015 Feb 13; 16:26. doi: 10.1186/s12891-015-0468-7.

12. Karateev AE, Alekseeva LI, Tsurgan AV, Gontarenko NA. Acute/subacute musculoskeletal pain therapy: results of ATUSA observational study (Analgesic Treatment Using a Systemic Algorithm). Terapevticheskii arkhiv. 2017;(12):175-84. (In Russ.).

13. Bickham K, Kivitz AJ, Mehta A, et al. Evaluation of two doses of etoricoxib, a COX-2 selective non-steroidal anti-inflammatory drug (NSAID), in the treatment of Rheumatoid Arthritis in a double-blind, randomized controlled trial. BMC Musculoskelet Disord. 2016 Aug 8;17:331. doi: 10.1186/s12891-016-1170-0.

14. Tarp S, Bartels EM, Bliddal H, et al. Effect of nonsteroidal antiinflammatory drugs on the C-reactive protein level in rheumatoid arthritis: a meta-analysis of randomized controlled trials. Arthritis Rheum. 2012 Nov; 64(11):3511-21. doi: 10.1002/art.34644.

15. Langdon CG, Moran DG, Jamieson V, et al. A multicentre study of tenoxicam for the treatment of osteoarthritis and rheumatoid arthritis in general practice. J Int Med Res. Nov-Dec 1990;18(6):489-96. doi: 10.1177/030006059001800607.

16. Lister BJ, Poland M, DeLapp RE. Efficacy of nabumetone versus diclofenac, naproxen, ibuprofen, and piroxicam in osteoarthritis and rheumatoid arthritis. Am J Med. 1993 Aug 9;95(2A):2S-9S. doi: 10.1016/0002-9343(93)90390-b.

17. Hunter JA, Parnham MJ, Balaguer XG. Aceclofenac in rheumatoid arthritis: a useful and novel anti-inflammatory. Clin Rheumatol. 1996 Jul;15(4):329-34. doi: 10.1007/BF02230353.

18. Pasero G, Marcolongo R, Serni U, et al. A multi-centre, double-blind comparative study of the efficacy and safety of aceclofenac and diclofenac in the treatment of rheumatoid arthritis. Curr Med Res Opin. 1995;13(6): 305-15. doi: 10.1185/03007999509110491.

19. Kornasoff D, Maisenbacher J, Bowdler J, Raber A. The efficacy and tolerability of aceclofenac compared to indomethacin in patients with rheumatoid arthritis. Rheumatol Int. 1996;15(6):225-30. doi: 10.1007/BF00290375.

20. Perez-Ruiz F, Alonso-Ruiz A, Ansoleaga J, et al. Comparative study of the efficacy and safety of aceclofenac and tenoxicam in rheumatoid arthritis. Clin Rheumatol. 1996 Sep;15(5):473-7. doi: 10.1007/BF02229644.

21. Martin-Mola E, Gijon-Banos J, Ansoleaga JJ. Aceclofenac in comparison to ketoprofen in the treatment of rheumatoid arthritis. Rheumatol Int. 1995;15(3):111-6. doi: 10.1007/BF00302127.

22. Dooley M, Spencer C, Dunn C. Aceclofenac: a reappraisal of its use in the management of pain and rheumatic disease. Drugs. 2001;61(9):1351-78. doi: 10.2165/00003495-200161090-00012.

23. Castellsague J, Riera-Guardia N, Calingaert B, et al. Individual NSAIDs and upper gastrointestinal complications: a systematic review and meta-analysis of observational studies (the SOS project). Drug Saf. 2012 Dec 1;35(12):1127-46. doi: 10.2165/11633470-000000000-00000.

24. Masclee GM, Straatman H, Arfe A, et al. Risk of acute myocardial infarction during use of individual NSAIDs: A nested casecontrol study from the SOS project. PLoS One. 2018 Nov 1;13(11):e0204746. doi: 10.1371/journal.pone.0204746. eCollection 2018.