Abstract
Objective
The aim of this study was to evaluate the efficacy, reasons for switching and drug survival of TNF-α inhibitors (TNFis) used as first- and second-line drugs in ankylosing spondylitis (AS).
Methods
Data on patients suffering from AS and treated with at least one TNFi between November 2005 and 2013 were extracted retrospectively from the database of a single clinical centre. Beside demographic data, the disease activity measured by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the response rates (BASDAI50), reasons for switching and survival curves of TNFis were analysed in general and in subgroups of patients treated with each of the available TNFis. The reasons for switching were defined as inefficacy, side effects of the given drug, patient’s request and occurrence of extra-articular manifestations.
Results
Altogether, 175 patients were on TNFis and 77 of them received at least two TNFis. The patients’ age at the initiation of the first TNFi was higher among switchers compared to non-switchers (42.5 ± 12.6 vs. 38.8 ± 11.2 years, p = 0.049); otherwise, gender, disease duration and initial disease activity had no influence on the risk of switching. The decrease of the BASDAI was similar among non-switchers and switchers using either the first or second TNFi, but the response rates to the first and second TNFi were worse in switchers than in non-switchers. Following the failure of the first TNFi, the retention on therapy was unfavourable, especially in patients on infliximab after 1 year of treatment. The main reason for switching from the first drug was inefficacy. The frequency of side effects that led to switching was higher in the infliximab group than in patients treated with other agents.
Conclusion
Although the retention rate to a second-line TNFi was somewhat worse than that to the first-line TNFi, the switching of TNFis is a good therapeutic option in AS patients who failed to respond to the first TNFi.
Similar content being viewed by others
References
van der Heijde, D., Pangan, A.L., Schiff, M.H., Braun, J., Borofsky, M., Torre, J., et al.: Adalimumab effectively reduces the signs and symptoms of active ankylosing spondylitis in patients with total spinal ankylosis. Ann. Rheum. Dis. 67(9), 1218–1221 (2008)
Davis Jr, J.C., Van der Heijde, D., Braun, J., Dougados, M., Cush, J., Clegg, D.O., et al.: Recombinant human tumor necrosis factor receptor (etanercept) for treating ankylosing spondylitis: a randomized, controlled trial. Arthritis Rheum. 48(11), 3230–3236 (2003)
Inman, R.D., Davis Jr, J.C., Heijde, D.v., Diekman, L., Sieper, J., Kim, S.I., et al.: Efficacy and safety of golimumab in patients with ankylosing spondylitis: results of a randomized, double-blind, placebo-controlled, phase III trial. Arthritis Rheum. 58(11), 3402–3412 (2008)
van der Heijde, D., Dijkmans, B., Geusens, P., Sieper, J., DeWoody, K., Williamson, P., et al.: Efficacy and safety of infliximab in patients with ankylosing spondylitis: results of a randomized, placebo-controlled trial (ASSERT). Arthritis Rheum. 52(2), 582–591 (2005)
Machado, M.A., Barbosa, M.M., Almeida, A.M., de Araújo, V.E., Kakehasi, A.M., Andrade, E.I., et al.: Treatment of ankylosing spondylitis with TNF blockers: a meta-analysis. Rheumatol. Int. 33(9), 2199–2213 (2013)
van der Heijde, D., Sieper, J., Maksymowych, W.P., Dougados, M., Burgos-Vargas, R., Landewé, R., et al.: 2010 Update of the international ASAS recommendations for the use of anti-TNF agents in patients with axial spondyloarthritis. Ann. Rheum. Dis. 70(6), 905–908 (2011)
Braun, J., van den Berg, R., Baraliakos, X., Boehm, H., Burgos-Vargas, R., Collantes-Estevez, E., et al.: 2010 update of the ASAS/EULAR recommendations for the management of ankylosing spondylitis. Ann. Rheum. Dis. 70(6), 896–904 (2011)
Elewaut, D., Matucci-Cerinic, M.: Treatment of ankylosing spondylitis and extra-articular manifestations in everyday rheumatology practice. Rheumatology (Oxford) 48(9), 1029–1035 (2009)
El Maghraoui, A.: Extra-articular manifestations of ankylosing spondylitis: prevalence, characteristics and therapeutic implications. Eur. J. Intern. Med. 22(6), 554–560 (2011)
Baraliakos, X., Listing, J., Fritz, C., Haibel, H., Alten, R., Burmester, G.R., et al.: Persistent clinical efficacy and safety of infliximab in ankylosing spondylitis after 8 years—early clinical response predicts long-term outcome. Rheumatology (Oxford) 50(9), 1690–1699 (2011)
Conti, F., Ceccarelli, F., Marocchi, E., Magrini, L., Spinelli, F.R., Spadaro, A., et al.: Switching tumour necrosis factor alpha antagonists in patients with ankylosing spondylitis and psoriatic arthritis: an observational study over a 5-year period. Ann. Rheum. Dis. 66(10), 1393–1397 (2007)
Landewé, R., Braun, J., Deodhar, A., Dougados, M., Maksymowych, W.P., Mease, P.J., et al.: Efficacy of certolizumab pegol on signs and symptoms of axial spondyloarthritis including ankylosing spondylitis: 24-week results of a double-blind randomised placebo-controlled Phase 3 study. Ann. Rheum. Dis. 73(1), 39–47 (2014)
Rudwaleit, M., Van den Bosch, F., Kron, M., Kary, S., Kupper, H.: Effectiveness and safety of adalimumab in patients with ankylosing spondylitis or psoriatic arthritis and history of anti-tumor necrosis factor therapy. Arthritis Res. Ther. 12(3), R117 (2010)
Glintborg, B., Østergaard, M., Krogh, N.S., Tarp, U., Manilo, N., Loft, A.G., et al.: Clinical response, drug survival and predictors thereof in 432 ankylosing spondylitis patients after switching tumour necrosis factor alpha inhibitor therapy: results from the Danish nationwide DANBIO registry. Ann. Rheum. Dis. 72(7), 1149–1155 (2013)
Lie, E., van der Heijde, D., Uhlig, T., Mikkelsen, K., Rødevand, E., Koldingsnes, W., et al.: Effectiveness of switching between TNF inhibitors in ankylosing spondylitis: data from the NOR-DMARD register. Ann. Rheum. Dis. 70(1), 157–163 (2011)
Hodinka, L.: The professional protocol of the Ministry of Health: the use of biological therapies in inflammatory rheumatic diseases. Magyar Reumatológia 50, 68–94 (2009)
Péntek, M., Brodszky, V., Gulácsi, A.L., Hajdú, O., van Exel, J., Brouwer, W., et al. Subjective expectations regarding length and health-related quality of life in Hungary: results from an empirical investigation. Health Expect. (2012)
Gulácsi, L., Brodszky, V., Péntek, M., Varga, S., Vas, G., Boncz, I.: History of health technology assessment in Hungary. Int. J. Technol. Assess. Health Care 25(Suppl 1), 120–126 (2009)
Gulácsi, L., Boncz, I., Drummond, M.: Issues for countries considering introducing the “fourth hurdle”: the case of Hungary. Int. J. Technol. Assess. Health Care 20(3), 337–341 (2004)
Gulácsi, L.: Future challenges for health economics and health technology assessment of biological drugs. Eur. J. Health Econ. 11(3), 235–238 (2010)
Gulácsi, L., Orlewska, E., Péntek, M.: Health economics and health technology assessment in Central and Eastern Europe: a dose of reality. Eur. J. Health Econ. 13(5), 525–531 (2012)
Brodszky, V., Orlewska, E., Pentek, M., Karpati, K., Skoupa, J., Gulacsi, L.: Challenges in economic evaluation of new drugs: experience with rituximab in Hungary. Med. Sci. Monit. 16(1), SR1–SR5 (2010)
Coates, L.C., Cawkwell, L.S., Ng, N.W., Bennett, A.N., Bryer, D.J., Fraser, A.D., et al.: Real life experience confirms sustained response to long-term biologics and switching in ankylosing spondylitis. Rheumatology (Oxford) 47(6), 897–900 (2008)
Pradeep, D.J., Keat, A.C., Gaffney, K., Brooksby, A., Leeder, J., Harris, C.: Switching anti-TNF therapy in ankylosing spondylitis. Rheumatology (Oxford) 47(11), 1726–1727 (2008)
Hu, S., Liang, S., Guo, H., Zhang, D., Li, H., Wang, X., et al.: Comparison of the inhibition mechanisms of adalimumab and infliximab in treating tumor necrosis factor alpha-associated diseases from a molecular view. J. Biol. Chem. 288(38), 27059–27067 (2013)
Plasencia, C., Pascual-Salcedo, D., García-Carazo, S., Lojo, L., Nuño, L., Villalba, A., et al.: The immunogenicity to the first anti-TNF therapy determines the outcome of switching to a second anti-TNF therapy in spondyloarthritis patients. Arthritis Res. Ther. 15(4), R79 (2013)
Garcês, S., Demengeot, J., Benito-Garcia, E.: The immunogenicity of anti-TNF therapy in immune-mediated inflammatory diseases: a systematic review of the literature with a meta-analysis. Ann. Rheum. Dis. 72(12), 1947–1955 (2013)
Acknowledgements
This research was supported by the European Union and the State of Hungary co-financed by the European Social Fund in the framework of TÁMOP-4.2.4.A/2-11/1-2012-0001 ‘National Excellence Program’.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Gulyas, K., Bodnar, N., Nagy, Z. et al. Real-life experience with switching TNF-α inhibitors in ankylosing spondylitis. Eur J Health Econ 15 (Suppl 1), 93–100 (2014). https://doi.org/10.1007/s10198-014-0598-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10198-014-0598-0