Abstract
The present study retrospectively assessed the efficacy of tocilizumab in patients with rheumatoid arthritis (RA) who failed to respond to treatment with etanercept or infliximab. A retrospective study of 33 RA patients who did not respond to etanercept or infliximab was conducted. Responses of subjects switching from etanercept to tocilizumab (n = 17) were compared with those switching from infliximab to tocilizumab (n = 16). Treatment with disease-modifying antirheumatic drugs before the switch, especially methotrexate (MTX), was maintained. Disease activity was assessed by the Disease Activity Score 28-C Reactive Protein (DAS28-CRP), the Simplified Disease Activity Index (SDAI), and the Clinical Disease Activity Index (CDAI). Patients who switched from etanercept were significantly less likely to have used MTX and were significantly older than patients who switched from infliximab. In both groups, there was a significant reduction from baseline in DAS28-CRP, SDAI, and CDAI values at 24 weeks with no significant differences between groups. However, at week 52, DAS28-CRP, SDAI, and CDAI values in the group switched from etanercept were significantly worse than those in the group switched from infliximab. All patients switched from infliximab were using MTX. In the evaluation between patients who switched from etanercept monotherapy, etanercept plus MTX, and infliximab plus MTX, a significant improvement from baseline was seen in DAS28-CRP, SDAI, and CDAI for all patients at 24 weeks with no significant differences between groups. Disease activity was maintained at 52 weeks in the group that switched from etanercept plus MTX and infliximab plus MTX. However, the efficacy of tocilizumab was decreased in the group that switched from etanercept monotherapy. Switching from etanercept plus MTX or from infliximab plus MTX to tocilizumab plus MTX improved response to therapy, but switching from etanercept monotherapy to tocilizumab monotherapy did not improve response to therapy.
Similar content being viewed by others
References
Tanaka Y, Takeuchi T, Inoue E, Saito K, Sekiguchi N, Sato E, Nawata M, Kameda H, Iwata S, Amano K, Yamanaka H (2008) Retrospective clinical study on the notable efficacy and related factors of infliximab therapy in a rheumatoid arthritis management group in Japan: one-year clinical outcomes (RECONFIRM-2). Mod Rheumatol 18:146–152
Wakabayashi H, Sudo A, Hasegawa M, Oka H, Uchida A, Nishioka K (2010) Retrospective clinical study of the efficacy of lower-dose methotrexate and infliximab therapy in patients with rheumatoid arthritis. Clin Rheumatol 29:671–675
Wiens A, Correr CJ, Venson R, Otuki MF, Pontarolo R (2010) A systematic review and meta-analysis of the efficacy and safety of adalimumab for treating rheumatoid arthritis. Rheumatol Int 30:1063–1070
Koike T, Harigai M, Inokuma S, Ishiguro N, Ryu J, Takeuchi T, Tanaka Y, Yamanaka H, Fujii K, Yoshinaga T, Freundlich B, Suzukawa M (2012) Safety and effectiveness responses to etanercept for rheumatoid arthritis in Japan: a sub-analysis of a post-marketing surveillance study focusing on the duration of rheumatoid arthritis. Rheumatol Int 32:1511–1519
Takeuchi T, Yamanaka H, Inoue E, Nagasawa H, Nawata M, Ikari K, Saito K, Sekiguchi N, Sato E, Kameda H, Iwata S, Mochizuki T, Amano K, Tanaka Y (2008) Retrospective clinical study on the notable efficacy and related factors of infliximab therapy in a rheumatoid arthritis management group in Japan: one-year outcome of joint destruction (RECONFIRM-2J). Mod Rheumatol 18:447–454
Haraoui B, Keystone EC, Thorne JC, Pope JE, Chen I, Asare CG, Leff JA (2004) Clinical outcomes of patients with rheumatoid arthritis after switching from infliximab to etanercept. J Rheumatol 31:2356–2359
Hyrich KL, Lunt M, Watson KD, Symmons DP, Silman AJ; British Society for Rheumatology Biologics Register (2007) Outcomes after switching from one anti-tumor necrosis factor alpha agent to a second anti-tumor necrosis factor alpha agent in patients with rheumatoid arthritis: results from a large UK national cohort study. Arthritis Rheum 56:13–20
Karlsson JA, Kristensen LE, Kapetanovic MC, Gülfe A, Saxne T, Geborek P (2008) Treatment response to a second or third TNF-inhibitor in RA: results from the South Swedish Arthritis Treatment Group Register. Rheumatology (Oxford) 47:507–513
Virkki LM, Valleala H, Takakubo Y, Vuotila J, Relas H, Komulainen R, Koivuniemi R, Yli-Kerttula U, Mali M, Sihvonen S, Krogerus ML, Jukka E, Nyrhinen S, Konttinen YT, Nordström DC (2011) Outcomes of switching anti-TNF drugs in rheumatoid arthritis—a study based on observational data from the Finnish Register of Biological Treatment (ROB-FIN). Clin Rheumatol 30:1447–1454
Smolen JS, Landewé R, Breedveld FC, Dougados M, Emery P, Gaujoux-Viala C, Gorter S, Knevel R, Nam J, Schoels M, Aletaha D, Buch M, Gossec L, Huizinga T, Bijlsma JW, Burmester G, Combe B, Cutolo M, Gabay C, Gomez-Reino J, Kouloumas M, Kvien TK, Martin-Mola E, McInnes I, Pavelka K, van Riel P, Scholte M, Scott DL, Sokka T, Valesini G, van Vollenhoven R, Winthrop KL, Wong J, Zink A, van der Heijde D (2010) EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs. Ann Rheum Dis 69:964–975
Inoue E, Yamanaka H, Hara M, Tomatsu T, Kamatani N (2007) Comparison of Disease Activity Score (DAS)28-erythrocyte sedimentation rate and DAS28-C-reactive protein threshold values. Ann Rheum Dis 66:407–409
Aletaha D, Smolen J (2005) The Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI): a review of their usefulness and validity in rheumatoid arthritis. Clin Exp Rheumatol 23:S100–S108
Kishimoto T (2006) Interleukin-6: discovery of a pleiotropic cytokine. Arthritis Res Ther 8:S2
Houssiau FA, Devogelaer JP, Van Damme J, de Deuxchaisnes CN, Van Snick J (1988) Interleukin-6 in synovial fluid and serum of patients with rheumatoid arthritis and other inflammatory arthritides. Arthritis Rheum 31:784–788
Madhok R, Crilly A, Watson J, Capell HA (1993) Serum interleukin 6 levels in rheumatoid arthritis: correlations with clinical and laboratory indices of disease activity. Ann Rheum Dis 52:232–234
Emery P, Keystone E, Tony HP, Cantagrel A, van Vollenhoven R, Sanchez A, Alecock E, Lee J, Kremer J (2008) IL-6 receptor inhibition with tocilizumab improves treatment outcomes in patients with rheumatoid arthritis refractory to anti-tumour necrosis factor biologicals: results from a 24-week multicentre randomised placebo-controlled trial. Ann Rheum Dis 67:1516–1523
Kawashiri SY, Kawakami A, Iwamoto N, Fujikawa K, Aramaki T, Tamai M, Arima K, Ichinose K, Kamachi M, Yamasaki S, Nakamura H, Origuchi T, Ida H, Eguchi K (2010) Switching to the anti-interleukin-6 receptor antibody tocilizumab in rheumatoid arthritis patients refractory to antitumor necrosis factor biologics. Mod Rheumatol 20:40–45
Wakabayashi H, Oka H, Nishioka Y, Hasegawa M, Sudo A, Nishioka K (2011) Do biologics-naïve patients with rheumatoid arthritis respond better to tocilizumab than patients for whom anti-TNF agents have failed? A retrospective study. Clin Exp Rheumatol 29:314–317
Marchesoni A, Zaccara E, Gorla R, Bazzani C, Sarzi-Puttini P, Atzeni F, Caporali R, Bobbio-Pallavicini F, Favalli EG (2009) TNF-alpha antagonist survival rate in a cohort of rheumatoid arthritis patients observed under conditions of standard clinical practice. Ann N Y Acad Sci 1173:837–846
Hetland ML, Christensen IJ, Tarp U, Dreyer L, Hansen A, Hansen IT, Kollerup G, Linde L, Lindegaard HM, Poulsen UE, Schlemmer A, Jensen DV, Jensen S, Hostenkamp G, Østergaard M, All Departments of Rheumatology in Denmark (2010) Direct comparison of treatment responses, remission rates, and drug adherence in patients with rheumatoid arthritis treated with adalimumab, etanercept, or infliximab: results from eight years of surveillance of clinical practice in the nationwide Danish DANBIO registry. Arthritis Rheum 62:22–32
Kameda H, Ueki Y, Saito K, Nagaoka S, Hidaka T, Atsumi T, Tsukano M, Kasama T, Shiozawa S, Tanaka Y, Takeuchi T; Japan Biological Agent Study Integrated Consortium (2010) Etanercept (ETN) with methotrexate (MTX) is better than ETN monotherapy in patients with active rheumatoid arthritis despite MTX therapy: a randomized trial. Mod Rheumatol 20:531–538
Nakashima Y, Kondo M, Harada H, Horiuchi T, Ishinishi T, Jojima H, Kuroda K, Miyahara H, Nagamine R, Nakashima H, Otsuka T, Saikawa I, Shono E, Suematsu E, Tsuru T, Wada K, Iwamoto Y (2010) Clinical evaluation of tocilizumab for patients with active rheumatoid arthritis refractory to anti-TNF biologics: tocilizumab in combination with methotrexate. Mod Rheumatol 20:343–352
Braun J, Kalden JR (2009) Biologics in the treatment of rheumatoid arthritis and ankylosing spondylitis. Clin Exp Rheumatol 27:S164–S167
Smolen JS, Aletaha D, Bijlsma JW, Breedveld FC, Boumpas D, Burmester G, Combe B, Cutolo M, de Wit M, Dougados M, Emery P, Gibofsky A, Gomez-Reino JJ, Haraoui B, Kalden J, Keystone EC, Kvien TK, McInnes I, Martin-Mola E, Montecucco C, Schoels M, van der Heijde D, T2T Expert Committee (2010) Treating rheumatoid arthritis to target: recommendations of an international task force. Ann Rheum Dis 69:631–637
Acknowledgments
We thank the staff of Nishioka Medical for their generous cooperation.
Funding
No benefits or funds were received in support of the study.
Disclosures
None.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Wakabayashi, H., Hasegawa, M., Nishioka, Y. et al. Clinical outcome in patients with rheumatoid arthritis switched to tocilizumab after etanercept or infliximab failure. Clin Rheumatol 32, 253–259 (2013). https://doi.org/10.1007/s10067-012-2118-x
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10067-012-2118-x