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Published in: Clinical Rheumatology 12/2023

23-09-2023 | Spondyloarthropathy | Original Article

Cause analysis of conversion to biologics in spondyloarthritis patients with poor response to conventional treatment

Authors: Jun Zhou, Wenhan Huang, Zhihuan Zhang, Lei Luo, Feifeng Ren, Dongmei Huang, Lin Tang

Published in: Clinical Rheumatology | Issue 12/2023

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Abstract

Objective

We sought to investigate the reasons why spondyloarthritis (SpA) patients failed to respond to non-steroidal anti-inflammatory drugs (NSAIDs) and conventional synthetic disease-modifying antirheumatic drugs (cDMARDs) and the influences of different initial cDMARDs on the likelihood of a switch to biologics.

Methods

SpA patients were divided into a conventional drug maintenance group and a biologics conversion group to determine the causes of conversion to biologics. Then, we divided all patients into three groups according to different initial cDMARDs, NSAID monotherapy, NSAID + (sulfasalazine or thalidomide) double combination, and NSAID + sulfasalazine + thalidomide triple combination therapy groups, to clarify the influence of initial treatment on later conversion to biologics.

Results

This study includes 202 patients, including 97 patients in the conventional drug maintenance group and 105 patients in the biologics conversion group. The mean age of the conventional drug maintenance group was higher than that of the biologics conversion group (40.8 ± 14.3 vs. 33.8 ± 12.3 years, P < 0.05). Uveitis (OR 5.356, P < 0.05) is positively correlated with conversion to biological therapy, while age (OR 0.940, P < 0.05) is negatively correlated. The proportion of NSAID monotherapy, double combination, and triple combination groups converted to biological agents was 80%, 51.1%, and 23.2%, respectively (P < 0.05).

Conclusion

Age and uveitis are related to conversion to biologics therapy. The early combination of sulfasalazine and thalidomide with NSAIDs may lower the probability of conversion to biologics therapy in the later stage and offer a new option for patients with limited use of biologics in SpA patients.
Key Points
• Patients’ move to biologics may be caused mostly by inadequate disease control by conventional oral medications.
• Regardless of axial vs. peripheral joint involvement, combination drug therapy was superior to single drug therapy in controlling SpA and decreasing the probability of conversion to a biological agent.
• For SpA patients who are not candidates for biologics due to contraindications or other reasons, early combination application of NSAIDs, sulfasalazine, and thalidomide may be a new choice.
Literature
1.
go back to reference Ward MM, Deodhar A, Gensler LS, Dubreuil M, Yu D, Khan MA et al (2019) 2019 Update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and treatment network recommendations for the treatment of ankylosing spondylitis and nonradiographic axial spondyloarthritis. Arthritis Rheum 71(10):1599–1613CrossRef Ward MM, Deodhar A, Gensler LS, Dubreuil M, Yu D, Khan MA et al (2019) 2019 Update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and treatment network recommendations for the treatment of ankylosing spondylitis and nonradiographic axial spondyloarthritis. Arthritis Rheum 71(10):1599–1613CrossRef
2.
go back to reference Schramm-Luc A, Schramm J, Siedlinski M, Guzik TJ, Batko B (2018) Age determines response to anti-TNFalpha treatment in patients with ankylosing spondylitis and is related to TNFalpha-producing CD8 cells. Clin Rheumatol 37(6):1597–1604CrossRefPubMedPubMedCentral Schramm-Luc A, Schramm J, Siedlinski M, Guzik TJ, Batko B (2018) Age determines response to anti-TNFalpha treatment in patients with ankylosing spondylitis and is related to TNFalpha-producing CD8 cells. Clin Rheumatol 37(6):1597–1604CrossRefPubMedPubMedCentral
3.
go back to reference Rudwaleit M, Listing J, Brandt J, Braun J, Sieper J (2004) Prediction of a major clinical response (BASDAI 50) to tumour necrosis factor alpha blockers in ankylosing spondylitis. Ann Rheum Dis 63(6):665–670CrossRefPubMedPubMedCentral Rudwaleit M, Listing J, Brandt J, Braun J, Sieper J (2004) Prediction of a major clinical response (BASDAI 50) to tumour necrosis factor alpha blockers in ankylosing spondylitis. Ann Rheum Dis 63(6):665–670CrossRefPubMedPubMedCentral
4.
go back to reference Zeboulon N, Dougados M, Gossec L (2008) Prevalence and characteristics of uveitis in the spondyloarthropathies: a systematic literature review. Ann Rheum Dis 67(7):955–959CrossRefPubMed Zeboulon N, Dougados M, Gossec L (2008) Prevalence and characteristics of uveitis in the spondyloarthropathies: a systematic literature review. Ann Rheum Dis 67(7):955–959CrossRefPubMed
5.
go back to reference Khan MA (1992) Spondyloarthropathies. Rheum Dis Clin N Am 18(1):1–276 Khan MA (1992) Spondyloarthropathies. Rheum Dis Clin N Am 18(1):1–276
6.
go back to reference Neri P, Zucchi M, Allegri P, Lettieri M, Mariotti C, Giovannini A (2011) Adalimumab (Humira): a promising monoclonal anti-tumor necrosis factor alpha in ophthalmology. Int Ophthalmol 31(2):165–173CrossRefPubMed Neri P, Zucchi M, Allegri P, Lettieri M, Mariotti C, Giovannini A (2011) Adalimumab (Humira): a promising monoclonal anti-tumor necrosis factor alpha in ophthalmology. Int Ophthalmol 31(2):165–173CrossRefPubMed
7.
go back to reference Rudwaleit M, Rodevand E, Holck P, Vanhoof J, Kron M, Kary S et al (2009) 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 68(5):696–701CrossRefPubMed Rudwaleit M, Rodevand E, Holck P, Vanhoof J, Kron M, Kary S et al (2009) 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 68(5):696–701CrossRefPubMed
8.
go back to reference Cronstein BN, Sitkovsky M (2017) Adenosine and adenosine receptors in the pathogenesis and treatment of rheumatic diseases. Nat Rev Rheumatol 13(1):41–51CrossRefPubMed Cronstein BN, Sitkovsky M (2017) Adenosine and adenosine receptors in the pathogenesis and treatment of rheumatic diseases. Nat Rev Rheumatol 13(1):41–51CrossRefPubMed
9.
go back to reference Katz KD, Hollander D (1989) Intestinal mucosal permeability and rheumatological diseases. Baillieres Clin Rheumatol 3(2):271–284CrossRefPubMed Katz KD, Hollander D (1989) Intestinal mucosal permeability and rheumatological diseases. Baillieres Clin Rheumatol 3(2):271–284CrossRefPubMed
10.
go back to reference Neumann VC, Shinebaum R, Cooke EM, Wright V (1987) Effects of sulphasalazine on faecal flora in patients with rheumatoid arthritis: a comparison with penicillamine. Br J Rheumatol 26(5):334–337CrossRefPubMed Neumann VC, Shinebaum R, Cooke EM, Wright V (1987) Effects of sulphasalazine on faecal flora in patients with rheumatoid arthritis: a comparison with penicillamine. Br J Rheumatol 26(5):334–337CrossRefPubMed
11.
go back to reference Hayllar J, Smith T, Macpherson A, Price AB, Gumpel M, Bjarnason I (1994) Nonsteroidal antiinflammatory drug-induced small intestinal inflammation and blood loss. Effects of sulfasalazine and other disease-modifying antirheumatic drugs. Arthritis Rheum 37(8):1146–1150CrossRefPubMed Hayllar J, Smith T, Macpherson A, Price AB, Gumpel M, Bjarnason I (1994) Nonsteroidal antiinflammatory drug-induced small intestinal inflammation and blood loss. Effects of sulfasalazine and other disease-modifying antirheumatic drugs. Arthritis Rheum 37(8):1146–1150CrossRefPubMed
12.
go back to reference Damjanov N, Shehhi WA, Huang F, Kotak S, Burgos-Vargas R, Shirazy K et al (2016) Assessment of clinical efficacy and safety in a randomized double-blind study of etanercept and sulfasalazine in patients with ankylosing spondylitis from Eastern/Central Europe, Latin America, and Asia. Rheumatol Int 36(5):643–651CrossRefPubMed Damjanov N, Shehhi WA, Huang F, Kotak S, Burgos-Vargas R, Shirazy K et al (2016) Assessment of clinical efficacy and safety in a randomized double-blind study of etanercept and sulfasalazine in patients with ankylosing spondylitis from Eastern/Central Europe, Latin America, and Asia. Rheumatol Int 36(5):643–651CrossRefPubMed
13.
go back to reference Braun J, Zochling J, Baraliakos X, Alten R, Burmester G, Grasedyck K et al (2006) Efficacy of sulfasalazine in patients with inflammatory back pain due to undifferentiated spondyloarthritis and early ankylosing spondylitis: a multicentre randomised controlled trial. Ann Rheum Dis 65(9):1147–1153CrossRefPubMedPubMedCentral Braun J, Zochling J, Baraliakos X, Alten R, Burmester G, Grasedyck K et al (2006) Efficacy of sulfasalazine in patients with inflammatory back pain due to undifferentiated spondyloarthritis and early ankylosing spondylitis: a multicentre randomised controlled trial. Ann Rheum Dis 65(9):1147–1153CrossRefPubMedPubMedCentral
14.
go back to reference Khanna Sharma S, Kadiyala V, Naidu G, Dhir V (2018) A randomized controlled trial to study the efficacy of sulfasalazine for axial disease in ankylosing spondylitis. Int J Rheum Dis 21(1):308–314CrossRefPubMed Khanna Sharma S, Kadiyala V, Naidu G, Dhir V (2018) A randomized controlled trial to study the efficacy of sulfasalazine for axial disease in ankylosing spondylitis. Int J Rheum Dis 21(1):308–314CrossRefPubMed
15.
go back to reference Yang PT, Xiao WG, Qin L, Zhao LJ, He LM, Ito M (2010) A pilot study on changes of macrophage colony stimulating factor and transforming growth factor beta1 in male patients with ankylosing spondylitis taking thalidomide. Ann Rheum Dis 69(4):781–782CrossRefPubMed Yang PT, Xiao WG, Qin L, Zhao LJ, He LM, Ito M (2010) A pilot study on changes of macrophage colony stimulating factor and transforming growth factor beta1 in male patients with ankylosing spondylitis taking thalidomide. Ann Rheum Dis 69(4):781–782CrossRefPubMed
16.
go back to reference Huang F, Wei JC, Breban M (2002) Thalidomide in ankylosing spondylitis. Clin Exp Rheumatol 20(6 Suppl 28):S158–S161PubMed Huang F, Wei JC, Breban M (2002) Thalidomide in ankylosing spondylitis. Clin Exp Rheumatol 20(6 Suppl 28):S158–S161PubMed
17.
go back to reference Wei JC, Chan TW, Lin HS, Huang F, Chou CT (2003) Thalidomide for severe refractory ankylosing spondylitis: a 6-month open-label trial. J Rheumatol 30(12):2627–2631PubMed Wei JC, Chan TW, Lin HS, Huang F, Chou CT (2003) Thalidomide for severe refractory ankylosing spondylitis: a 6-month open-label trial. J Rheumatol 30(12):2627–2631PubMed
18.
go back to reference Davis JC Jr, Huang F, Maksymowych W (2003) New therapies for ankylosing spondylitis: etanercept, thalidomide, and pamidronate. Rheum Dis Clin N Am 29(3):481–494 viiiCrossRef Davis JC Jr, Huang F, Maksymowych W (2003) New therapies for ankylosing spondylitis: etanercept, thalidomide, and pamidronate. Rheum Dis Clin N Am 29(3):481–494 viiiCrossRef
19.
go back to reference Zhang S, Chen Z, Wu Y, Lin D, He J, Liu J et al (2021) Efficacy and safety of thalidomide on psychological symptoms and sleep disturbances in the patient with refractory ankylosing spondylitis. Ann Palliat Med 10(3):2512–2519CrossRefPubMed Zhang S, Chen Z, Wu Y, Lin D, He J, Liu J et al (2021) Efficacy and safety of thalidomide on psychological symptoms and sleep disturbances in the patient with refractory ankylosing spondylitis. Ann Palliat Med 10(3):2512–2519CrossRefPubMed
20.
go back to reference Zhu J, Huang F, Zhang JL (2010) The efficacy and safety of long-term thalidomide in the treatment of ankylosing spondylitis. Zhonghua Nei Ke Za Zhi 49(8):667–670PubMed Zhu J, Huang F, Zhang JL (2010) The efficacy and safety of long-term thalidomide in the treatment of ankylosing spondylitis. Zhonghua Nei Ke Za Zhi 49(8):667–670PubMed
Metadata
Title
Cause analysis of conversion to biologics in spondyloarthritis patients with poor response to conventional treatment
Authors
Jun Zhou
Wenhan Huang
Zhihuan Zhang
Lei Luo
Feifeng Ren
Dongmei Huang
Lin Tang
Publication date
23-09-2023
Publisher
Springer International Publishing
Published in
Clinical Rheumatology / Issue 12/2023
Print ISSN: 0770-3198
Electronic ISSN: 1434-9949
DOI
https://doi.org/10.1007/s10067-023-06724-3

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