Skip to main content
Top
Published in: Clinical Rheumatology 1/2021

01-01-2021 | Methotrexate | Original Article

Clinical effectiveness of iguratimod based on real-world data of patients with rheumatoid arthritis

Authors: Satoshi Mizutani, Hitoshi Kodera, Yoshiko Sato, Toshihiro Nanki, Shunji Yoshida, Hidekata Yasuoka

Published in: Clinical Rheumatology | Issue 1/2021

Login to get access

Abstract

Objectives

Iguratimod (IGU) is a conventional synthetic disease-modifying drug that has been approved based on its additive effects with methotrexate (MTX) for the treatment of rheumatoid arthritis (RA). The objective of the study is to establish the effectiveness of IGU with versus IGU without MTX irrespective of whether MTX is well tolerated or not by the patients.

Methods

Disease activity scores in 177 RA patients treated using IGU were retrospectively evaluated at baseline and after 4, 12, and 24 weeks, and adverse events (AEs) were noted.

Results

IGU reduced the disease activity parameters, disease activity score (DAS)-ESR, DAS-CRP, the simplified disease activity index (SDAI), and clinical disease activity index (CDAI) in the concomitant MTX and non-MTX, female and male, and young and elderly patient groups after 24 weeks. Multivariate analysis demonstrated that IGU was more effective with concomitant MTX and in elderly and male patients. Severe AEs were observed only in the elderly group: two cases of pneumonia, 1 of pneumocystis pneumonia, 1 of heart failure, and 1 of salivary gland adenoma.

Conclusions

IGU is effective for RA, especially with concomitant MTX, and in elderly and male patients.
Key Points
Iguratimod is effective for RA, especially with concomitant MTX, and in elderly and male patients.
Since all serious adverse events were in the elderly group in this study, sufficient monitoring for adverse events, especially for elderly RA patients, is needed during iguratimod therapy.
Literature
1.
go back to reference Tanaka K, Aikawa Y, Kawasaki H, Asaoka K, Inaba T, Yoshida C (1992) Pharmacological studies on 3-formylamino-7-methylsulfonylamino-6-phenoxy-4H-1-benzopyran-4-one (T-614), a novel antiinflammatory agent. 4th communication: inhibitory effect on the production of interleukin-1 and interleukin-6. Aust J Pharm 15(11):649–655 Tanaka K, Aikawa Y, Kawasaki H, Asaoka K, Inaba T, Yoshida C (1992) Pharmacological studies on 3-formylamino-7-methylsulfonylamino-6-phenoxy-4H-1-benzopyran-4-one (T-614), a novel antiinflammatory agent. 4th communication: inhibitory effect on the production of interleukin-1 and interleukin-6. Aust J Pharm 15(11):649–655
2.
go back to reference Tanaka K, Makino S, Shimotori T, Aikawa Y, Inaba T, Yoshida C (1992) Pharmacological studies of the new antiinflammatory agent 3-formylamino-7-methylsulfonylamino-6-phenoxy-4′-1-benzopyran-4-o ne. 2nd communication: effect on the arachidonic acid cascades. Arzneimittelforschung 42(7):945–950PubMed Tanaka K, Makino S, Shimotori T, Aikawa Y, Inaba T, Yoshida C (1992) Pharmacological studies of the new antiinflammatory agent 3-formylamino-7-methylsulfonylamino-6-phenoxy-4′-1-benzopyran-4-o ne. 2nd communication: effect on the arachidonic acid cascades. Arzneimittelforschung 42(7):945–950PubMed
3.
go back to reference Tanaka K, Shimotori T, Makino S, Aikawa Y, Inaba T, Yoshida C, Takano S (1992) Pharmacological studies of the new antiinflammatory agent 3-formylamino-7-methylsulfonylamino-6-phenoxy-4H-1-benzopyran-4-o ne. 1st communication: antiinflammatory, analgesic and other related properties. Arzneimittelforschung 42(7):935–944PubMed Tanaka K, Shimotori T, Makino S, Aikawa Y, Inaba T, Yoshida C, Takano S (1992) Pharmacological studies of the new antiinflammatory agent 3-formylamino-7-methylsulfonylamino-6-phenoxy-4H-1-benzopyran-4-o ne. 1st communication: antiinflammatory, analgesic and other related properties. Arzneimittelforschung 42(7):935–944PubMed
4.
go back to reference Tanaka K, Shimotori T, Makino S, Eguchi M, Asaoka K, Kitamura R, Yoshida C (1992) Pharmacological studies on 3-formylamino-7-methylsulfonylamino-6-phenoxy-4H-1-benzopyran-4-one (T-614), a novel antiinflammatory agent. 3rd communication: the involvement of bradykinin in its analgesic actions. Aust J Pharm 15(11):641–647 Tanaka K, Shimotori T, Makino S, Eguchi M, Asaoka K, Kitamura R, Yoshida C (1992) Pharmacological studies on 3-formylamino-7-methylsulfonylamino-6-phenoxy-4H-1-benzopyran-4-one (T-614), a novel antiinflammatory agent. 3rd communication: the involvement of bradykinin in its analgesic actions. Aust J Pharm 15(11):641–647
6.
go back to reference Aikawa Y, Yamamoto M, Yamamoto T, Morimoto K, Tanaka K (2002) An anti-rheumatic agent T-614 inhibits NF-kappaB activation in LPS- and TNF-alpha-stimulated THP-1 cells without interfering with IkappaBalpha degradation. Inflamm Res 51(4):188–194CrossRef Aikawa Y, Yamamoto M, Yamamoto T, Morimoto K, Tanaka K (2002) An anti-rheumatic agent T-614 inhibits NF-kappaB activation in LPS- and TNF-alpha-stimulated THP-1 cells without interfering with IkappaBalpha degradation. Inflamm Res 51(4):188–194CrossRef
7.
go back to reference Kawakami A, Tsuboi M, Urayama S, Matsuoka N, Yamasaki S, Hida A, Aoyagi T, Furuichi I, Nakashima T, Migita K, Kawabe Y, Nakashima M, Origuchi T, Eguchi K (1999) Inhibitory effect of a new anti-rheumatic drug T-614 on costimulatory molecule expression, cytokine production, and antigen presentation by synovial cells. J Lab Clin Med 133(6):566–574CrossRef Kawakami A, Tsuboi M, Urayama S, Matsuoka N, Yamasaki S, Hida A, Aoyagi T, Furuichi I, Nakashima T, Migita K, Kawabe Y, Nakashima M, Origuchi T, Eguchi K (1999) Inhibitory effect of a new anti-rheumatic drug T-614 on costimulatory molecule expression, cytokine production, and antigen presentation by synovial cells. J Lab Clin Med 133(6):566–574CrossRef
8.
go back to reference Kohno M, Aikawa Y, Tsubouchi Y, Hashiramoto A, Yamada R, Kawahito Y, Inoue K, Kusaka Y, Kondo M, Sano H (2001) Inhibitory effect of T-614 on tumor necrosis factor-alpha induced cytokine production and nuclear factor-kappaB activation in cultured human synovial cells. J Rheumatol 28(12):2591–2596PubMed Kohno M, Aikawa Y, Tsubouchi Y, Hashiramoto A, Yamada R, Kawahito Y, Inoue K, Kusaka Y, Kondo M, Sano H (2001) Inhibitory effect of T-614 on tumor necrosis factor-alpha induced cytokine production and nuclear factor-kappaB activation in cultured human synovial cells. J Rheumatol 28(12):2591–2596PubMed
9.
go back to reference Tanaka K, Yamamoto T, Aikawa Y, Kizawa K, Muramoto K, Matsuno H, Muraguchi A (2003) Inhibitory effects of an anti-rheumatic agent T-614 on immunoglobulin production by cultured B cells and rheumatoid synovial tissues engrafted into SCID mice. Rheumatology (Oxford) 42(11):1365–1371. https://doi.org/10.1093/rheumatology/keg381CrossRef Tanaka K, Yamamoto T, Aikawa Y, Kizawa K, Muramoto K, Matsuno H, Muraguchi A (2003) Inhibitory effects of an anti-rheumatic agent T-614 on immunoglobulin production by cultured B cells and rheumatoid synovial tissues engrafted into SCID mice. Rheumatology (Oxford) 42(11):1365–1371. https://​doi.​org/​10.​1093/​rheumatology/​keg381CrossRef
10.
go back to reference Hara M, Abe T, Sugawara S, Mizushima Y, Hoshi K, Irimajiri S, Hashimoto H, Yoshino S, Matsui N, Nobunaga M, Nakano S (2007) Efficacy and safety of iguratimod compared with placebo and salazosulfapyridine in active rheumatoid arthritis: a controlled, multicenter, double-blind, parallel-group study. Mod Rheumatol 17(1):1–9. https://doi.org/10.1007/s10165-006-0542-yCrossRefPubMed Hara M, Abe T, Sugawara S, Mizushima Y, Hoshi K, Irimajiri S, Hashimoto H, Yoshino S, Matsui N, Nobunaga M, Nakano S (2007) Efficacy and safety of iguratimod compared with placebo and salazosulfapyridine in active rheumatoid arthritis: a controlled, multicenter, double-blind, parallel-group study. Mod Rheumatol 17(1):1–9. https://​doi.​org/​10.​1007/​s10165-006-0542-yCrossRefPubMed
12.
go back to reference Hara M, Ishiguro N, Katayama K, Kondo M, Sumida T, Mimori T, Soen S, Nagai K, Yamaguchi T, Yamamoto K, Iguratimod-Clinical Study G (2014) Safety and efficacy of combination therapy of iguratimod with methotrexate for patients with active rheumatoid arthritis with an inadequate response to methotrexate: an open-label extension of a randomized, double-blind, placebo-controlled trial. Mod Rheumatol 24(3):410–418. https://doi.org/10.3109/14397595.2013.843756CrossRefPubMed Hara M, Ishiguro N, Katayama K, Kondo M, Sumida T, Mimori T, Soen S, Nagai K, Yamaguchi T, Yamamoto K, Iguratimod-Clinical Study G (2014) Safety and efficacy of combination therapy of iguratimod with methotrexate for patients with active rheumatoid arthritis with an inadequate response to methotrexate: an open-label extension of a randomized, double-blind, placebo-controlled trial. Mod Rheumatol 24(3):410–418. https://​doi.​org/​10.​3109/​14397595.​2013.​843756CrossRefPubMed
13.
go back to reference Singh JA, Saag KG, Bridges SL Jr, Akl EA, Bannuru RR, Sullivan MC, Vaysbrot E, McNaughton C, Osani M, Shmerling RH, Curtis JR, Furst DE, Parks D, Kavanaugh A, O'Dell J, King C, Leong A, Matteson EL, Schousboe JT, Drevlow B, Ginsberg S, Grober J, St Clair EW, Tindall E, Miller AS, McAlindon T (2016) 2015 American College of Rheumatology Guideline for the treatment of rheumatoid arthritis. Arthritis Rheum 68(1):1–26. https://doi.org/10.1002/art.39480CrossRef Singh JA, Saag KG, Bridges SL Jr, Akl EA, Bannuru RR, Sullivan MC, Vaysbrot E, McNaughton C, Osani M, Shmerling RH, Curtis JR, Furst DE, Parks D, Kavanaugh A, O'Dell J, King C, Leong A, Matteson EL, Schousboe JT, Drevlow B, Ginsberg S, Grober J, St Clair EW, Tindall E, Miller AS, McAlindon T (2016) 2015 American College of Rheumatology Guideline for the treatment of rheumatoid arthritis. Arthritis Rheum 68(1):1–26. https://​doi.​org/​10.​1002/​art.​39480CrossRef
14.
go back to reference Smolen JS, Landewe R, Bijlsma J, Burmester G, Chatzidionysiou K, Dougados M, Nam J, Ramiro S, Voshaar M, van Vollenhoven R, Aletaha D, Aringer M, Boers M, Buckley CD, Buttgereit F, Bykerk V, Cardiel M, Combe B, Cutolo M, van Eijk-Hustings Y, Emery P, Finckh A, Gabay C, Gomez-Reino J, Gossec L, Gottenberg JE, Hazes JM, Huizinga T, Jani M, Karateev D, Kouloumas M, Kvien T, Li Z, Mariette X, McInnes I, Mysler E, Nash P, Pavelka K, Poor G, Richez C, van Riel P, Rubbert-Roth A, Saag K, da Silva J, Stamm T, Takeuchi T, Westhovens R, de Wit M, van der Heijde D (2017) EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis 76:960–977. https://doi.org/10.1136/annrheumdis-2016-210715CrossRefPubMed Smolen JS, Landewe R, Bijlsma J, Burmester G, Chatzidionysiou K, Dougados M, Nam J, Ramiro S, Voshaar M, van Vollenhoven R, Aletaha D, Aringer M, Boers M, Buckley CD, Buttgereit F, Bykerk V, Cardiel M, Combe B, Cutolo M, van Eijk-Hustings Y, Emery P, Finckh A, Gabay C, Gomez-Reino J, Gossec L, Gottenberg JE, Hazes JM, Huizinga T, Jani M, Karateev D, Kouloumas M, Kvien T, Li Z, Mariette X, McInnes I, Mysler E, Nash P, Pavelka K, Poor G, Richez C, van Riel P, Rubbert-Roth A, Saag K, da Silva J, Stamm T, Takeuchi T, Westhovens R, de Wit M, van der Heijde D (2017) EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis 76:960–977. https://​doi.​org/​10.​1136/​annrheumdis-2016-210715CrossRefPubMed
15.
go back to reference Atsumi T, Yamamoto K, Takeuchi T, Yamanaka H, Ishiguro N, Tanaka Y, Eguchi K, Watanabe A, Origasa H, Yasuda S, Yamanishi Y, Kita Y, Matsubara T, Iwamoto M, Shoji T, Okada T, van der Heijde D, Miyasaka N, Koike T (2016) The first double-blind, randomised, parallel-group certolizumab pegol study in methotrexate-naive early rheumatoid arthritis patients with poor prognostic factors, C-OPERA, shows inhibition of radiographic progression. Ann Rheum Dis 75(1):75–83. https://doi.org/10.1136/annrheumdis-2015-207511CrossRefPubMed Atsumi T, Yamamoto K, Takeuchi T, Yamanaka H, Ishiguro N, Tanaka Y, Eguchi K, Watanabe A, Origasa H, Yasuda S, Yamanishi Y, Kita Y, Matsubara T, Iwamoto M, Shoji T, Okada T, van der Heijde D, Miyasaka N, Koike T (2016) The first double-blind, randomised, parallel-group certolizumab pegol study in methotrexate-naive early rheumatoid arthritis patients with poor prognostic factors, C-OPERA, shows inhibition of radiographic progression. Ann Rheum Dis 75(1):75–83. https://​doi.​org/​10.​1136/​annrheumdis-2015-207511CrossRefPubMed
16.
go back to reference Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS et al (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31(3):315–324CrossRef Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS et al (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31(3):315–324CrossRef
17.
go back to reference Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd, Birnbaum NS, Burmester GR, Bykerk VP, Cohen MD, Combe B, Costenbader KH, Dougados M, Emery P, Ferraccioli G, Hazes JM, Hobbs K, Huizinga TW, Kavanaugh A, Kay J, Kvien TK, Laing T, Mease P, Menard HA, Moreland LW, Naden RL, Pincus T, Smolen JS, Stanislawska-Biernat E, Symmons D, Tak PP, Upchurch KS, Vencovsky J, Wolfe F, Hawker G (2010) 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis 69(9):1580–1588. https://doi.org/10.1136/ard.2010.138461CrossRef Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd, Birnbaum NS, Burmester GR, Bykerk VP, Cohen MD, Combe B, Costenbader KH, Dougados M, Emery P, Ferraccioli G, Hazes JM, Hobbs K, Huizinga TW, Kavanaugh A, Kay J, Kvien TK, Laing T, Mease P, Menard HA, Moreland LW, Naden RL, Pincus T, Smolen JS, Stanislawska-Biernat E, Symmons D, Tak PP, Upchurch KS, Vencovsky J, Wolfe F, Hawker G (2010) 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis 69(9):1580–1588. https://​doi.​org/​10.​1136/​ard.​2010.​138461CrossRef
20.
go back to reference Steinbrocker O, Traeger CH, Batterman RC (1949) Therapeutic criteria in rheumatoid arthritis. J Am Med Assoc 140(8):659–662CrossRef Steinbrocker O, Traeger CH, Batterman RC (1949) Therapeutic criteria in rheumatoid arthritis. J Am Med Assoc 140(8):659–662CrossRef
25.
go back to reference Mimori T, Harigai M, Atsumi T, Fujii T, Kuwana M, Matsuno H, Momohara S, Takei S, Tamura N, Takasaki Y, Ikeuchi S, Kushimoto S, Koike T (2017) Safety and effectiveness of 24-week treatment with iguratimod, a new oral disease-modifying antirheumatic drug, for patients with rheumatoid arthritis: interim analysis of a post-marketing surveillance study of 2679 patients in Japan. Mod Rheumatol 27(5):755–765. https://doi.org/10.1080/14397595.2016.1265695CrossRefPubMed Mimori T, Harigai M, Atsumi T, Fujii T, Kuwana M, Matsuno H, Momohara S, Takei S, Tamura N, Takasaki Y, Ikeuchi S, Kushimoto S, Koike T (2017) Safety and effectiveness of 24-week treatment with iguratimod, a new oral disease-modifying antirheumatic drug, for patients with rheumatoid arthritis: interim analysis of a post-marketing surveillance study of 2679 patients in Japan. Mod Rheumatol 27(5):755–765. https://​doi.​org/​10.​1080/​14397595.​2016.​1265695CrossRefPubMed
Metadata
Title
Clinical effectiveness of iguratimod based on real-world data of patients with rheumatoid arthritis
Authors
Satoshi Mizutani
Hitoshi Kodera
Yoshiko Sato
Toshihiro Nanki
Shunji Yoshida
Hidekata Yasuoka
Publication date
01-01-2021
Publisher
Springer International Publishing
Published in
Clinical Rheumatology / Issue 1/2021
Print ISSN: 0770-3198
Electronic ISSN: 1434-9949
DOI
https://doi.org/10.1007/s10067-020-05208-y

Other articles of this Issue 1/2021

Clinical Rheumatology 1/2021 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.