OBJECTIVES: To assess clinical response after switching between anti-tumor necrosis factor-alpha (anti-TNF-alpha) agents in patients with rheumatoid arthritis (RA). PATIENTS AND METHODS: This study included 99 patients diagnosed with RA American College of Rheumatology, 1987), on anti-TNF-alpha therapy, to assess the therapeutic response after 24 weeks. Switching was performed if, after 12 to 24 weeks, a severe adverse event was reported (toxicity: T) or if no reduction greater than 0.6 in the initial Disease Activity Score 28 (DAS28) occurred (inadequate response: IR). In case of IR, the patient was considered as primary failure (PF). Secondary failure (SF) was defined as loss of response after initial improvement. Remission (DAS28 < 2.6), low disease activity (between 2.61 and 3.2), and functional improvement [increase in the initial Health Assessment Questionnaire (HAQ) > 0.2] were assessed by use of linear regression analysis. The significance level adopted was P < 0.05. RESULTS: Switching was performed in 39 (39.4%) patients, especially due to PF (24.3%), SF (35.1%) and T (40.5%). The retention rate of the first agent was 60.1%, and the mean time for switching was 14.2 ± 10.9 months. After switching, a tendency towards a decrease in DAS28 was observed (4.7 ± 1.4; P = 0.08), but not in the HAQ (1.2 ± 0.77; P = 0.11). Around 43% of the patients achieved good/moderate EULAR response. The major determinant of switching was a higher initial DAS28, independent of age, duration of disease, and functional capacity. CONCLUSION: Switching between anti-TNF-alpha agents is a valid strategy to control disease activity, despite the low likelihood of remission and no significant improvement in functional capacity
rheumatoid arthritis; anti-TNF therapy; disease activity; switching; functional capacity
OBJETIVOS: Avaliar a resposta clínica após a estratégia de troca entre agentes antifator de necrose tumoral alfa (anti-TNF-alfa) em pacientes com artrite reumatoide (AR). PACIENTES E MÉTODOS: Foram incluídos 99 pacientes com diagnóstico de AR (American College of Rheumatology, 1987), em uso de terapia anti-TNF-alfa, para avaliação da resposta terapêutica após 24 semanas. A estratégia de troca foi feita se, após 12 a 24 semanas, houvesse relato de evento adverso sério (T: toxicidade) ou se não ocorresse redução maior que 0,6 do índice de atividade da doença (DAS28) inicial (RI: resposta inadequada). Nesse último caso, o paciente foi considerado como falência primária (FP). Falência secundária (FS) foi definida se houvesse perda de resposta após melhora inicial. Remissão (DAS28 < 2,6), baixa atividade de doença (2,61 < 3,2) e melhora funcional [aumento > 0,2 do questionário de avaliação da saúde (HAQ) inicial] foram avaliadas por análise de regressão linear. P < 0,05 foi considerado significante. RESULTADOS: A estratégia de troca foi realizada em 39 (39,4%) pacientes, especialmente por FP (24,3%), FS (35,1%) e T (40,5%). A taxa de retenção ao primeiro agente foi de 60,1%, e o tempo médio para a troca foi de 14,2 ± 10,9 meses. Após a troca, houve tendência à queda do DAS28 (4,7 ± 1,4; P = 0,08), mas não do HAQ (1,2 ± 0,77; P = 0,11). Cerca de 43% deles alcançaram boa/moderada resposta EULAR. O principal determinante da troca foi o DAS28 inicial mais elevado, independente de idade, tempo de doença e capacidade funcional. CONCLUSÃO: A estratégia de troca entre agentes anti-TNF-alfa é válida para o controle da atividade de doença, embora com baixa probabilidade de remissão e sem melhora significativa da capacidade funcional
artrite reumatoide; terapia anti-TNF-alfa; atividade da doença; switching; capacidade funcional
IPost-graduation student in Rheumatology, Universidade Federal de São Paulo - UNIFESP
IIPhD, Assistant Professor of the Discipline of Rheumatology and of the Centro Paulista de Economia e Saúde (CPES), UNIFESP
IIIPhD, Assistant Professor, and Chief of the Spondyloarthritides and Osteoporosis Outpatient Clinic of the Discipline of the Rheumatology, UNIFESP
OBJECTIVES:To assess clinical response after switching between anti-tumor necrosis factor-alpha (anti-TNF-alpha) agents in patients with rheumatoid arthritis (RA).
PATIENTS AND METHODS:This study included 99 patients diagnosed with RA (American College of Rheumatology, 1987), on anti-TNF-alpha therapy, to assess the therapeutic response after 24 weeks. Switching was performed if, after 12 to 24 weeks, a severe adverse event was reported (toxicity: T) or if no reduction greater than 0.6 in the initial Disease Activity Score 28 (DAS28) occurred (inadequate response: IR). In case of IR, the patient was considered as primary failure (PF). Secondary failure (SF) was defined as loss of response after initial improvement. Remission (DAS28 < 2.6), low disease activity (between 2.61 and 3.2), and functional improvement [increase in the initial Health Assessment Questionnaire (HAQ) > 0.2] were assessed by use of linear regression analysis. The significance level adopted was P < 0.05.
RESULTS: Switching was performed in 39 (39.4%) patients, especially due to PF (24.3%), SF (35.1%) and T (40.5%). The retention rate of the first agent was 60.1%, and the mean time for switching was 14.2 ± 10.9 months. After switching, a tendency towards a decrease in DAS28 was observed (4.7 ± 1.4; P = 0.08), but not in the HAQ (1.2 ± 0.77; P = 0.11). Around 43% of the patients achieved good/moderate EULAR response. The major determinant of switching was a higher initial DAS28, independent of age, duration of disease, and functional capacity.
CONCLUSION: Switching between anti-TNF-alpha agents is a valid strategy to control disease activity, despite the low likelihood of remission and no significant improvement in functional capacity.
Keywords: rheumatoid arthritis, anti-TNF therapy, disease activity, switching, functional capacity.
In the past decade, the treatment of rheumatoid arthritis (RA) underwent great changes with the introduction of anti-tumor necrosis factor-alpha (anti-TNF-alpha) agents, and especially with the advances in clinical and radiographic control of the disease. However, some patients either do not respond, or respond only partially, to TNF-alpha inhibitors. In addition, patients who initially responded can experience either a decrease in the efficacy of TNF-alpha inhibitors over time, or adverse events, requiring new therapeutic strategies.
In Brazil, infliximab (IFX), etanercept (ETN), and adalimumab (ADA) are currently available, being usually associated with methotrexate (MTX) or other disease-modifying antirheumatic drugs (DMARDs), except when intolerance or toxicity occurs. Although anti-TNF-alpha agents have similar clinical efficacy and costs, they differ in the following aspects: molecular structure; pharmacokinetics; mechanism of action; potential to form autoantibodies, and human anti-chimeric (HACA) or human anti-human (HAHA) antibodies; induction of apoptosis; and posology.1-3 Thus, switching from one anti-TNF-alpha agent to another might be a treatment option in patients experiencing loss of efficacy or intolerance to the first treatment.1,2
This study aimed at assessing the clinical response, especially functional capacity, after switching from one anti-TNF-alpha agent to another in patients with active, long-standing RA, and who had failed to respond to DMARDs, including MTX.
PATIENTS AND METHODS
From January 2004 to January 2010, a retrospective analysis of the database of patients followed up at the Outpatient Clinic of Rheumatoid Arthritis and Biologics of the Discipline of Rheumatology of Escola Paulista de Medicina, Universidade Federal de São Paulo (EPM/UNIFESP), was carried out. All patients diagnosed with RA, according to the American College of Rheumatology 1987 classification criteria,4 and on anti-TNF-alpha therapy5 were included in the study.
Approximately 1,300 patients diagnosed with RA are annually followed up at that service, and 99 of them (7.6%) met the inclusion criteria of this study. Of those 99 patients, 39 (39%) underwent switching of the anti-TNF-alpha agent during follow-up, and were included in this analysis.
The non-inclusion criterion adopted was lack of data (initial and after six months). In addition, patients with the following characteristics were excluded: global functional status class IV;6 inability to answer the questionnaires; other autoimmune rheumatic diseases; neoplasias; and other disabling diseases. From this cohort, only two patients were excluded, due to lack of follow-up data after switching.
The reasons for discontinuing the first anti-TNF-alpha agent were classified as follows: primary failure (PF); secondary failure (SF); adverse event (AE); and consent withdrawal (personal reasons, travel, loss to follow-up). Primary failure was defined as a DAS28 (Disease Activity Score 28) reduction lower than 0.6 after 12 weeks [no EULAR (EUropean League Against Rheumatism) response]. Secondary failure was defined as loss of efficacy (a DAS28 increase over 0.6 from the initial value) over 24 weeks in patients who had responded in the first 12 weeks, based on a DAS28 reduction greater than 0.6.7
Adverse event was defined as any medical occurrence not initially predicted, which appeared after switching the anti-TNF-alpha therapy. Severe AE was defined as any medical occurrence not initially predicted and that resulted in death, caused danger of death, or required or extended the ongoing hospitalization. Such events might, but not necessarily, have causal relation to the research procedures.8
Clinical and laboratory assessments included DAS28, erythrocyte sedimentation rate (ESR), and the Brazilian modified version of the Health Assessment Questionnaire (HAQ).9,10 All measures were performed before treatment and three and six months after. Response to therapy was assessed according to both the DAS28 reduction and the criteria proposed by EULAR7 (no response: a reduction lower than 0.6 between two consecutive measures; moderate: a reduction between 0.6 and 1.2; good: a reduction greater than 1.2). Clinical remission was defined as a DAS28 lower than 2.6.10 Demographic data and disease characteristics were also included in the analysis. The synthetic DMARDs being used at the time of switching anti-TNF-alpha agents were not modified until the end of the reassessment (after 24 weeks), including stable dose and type of association.
The major risk factors associated with discontinuation were assessed by use of univariate linear regression and logistic regression. Three models were built, having the following dependent variables: HAQ (reduction of at least 0.2) in the first; moderate/good EULAR response (reduction greater than 0.6) in the second; and remission (DAS28 < 2.6) in the third. All other variables were considered as independent. For the statistical analysis, the SPSS (Statistical Package for Social Science) software, version 15.0, was used. The significance level adopted was P < 0.05.
At the end of the study, 37 patients were analyzed. Their mean age was 52 years, and the female gender predominated (89.3%). Most patients had long-standing and erosive disease, as well as high positivity for rheumatoid factor and impaired functional capacity (Steinbrocker functional class II and III)6 (Table 1).
Similarly, most patients were using prednisone, at a mean daily dose of almost 10 mg. Almost 50% of the patients were using MTX in combination with TNF-alpha inhibitors, at a mean weekly dose close to 25 mg. In addition, slightly more than 80% of the patients were using leflunomide (LFN) in association with anti-TNF-alpha agents. Of those, 21.6% were on an association of LFN and MTX (Table 2).
Before using the first anti-TNF-alpha agent, almost 20% of the patients received isoniazid for treating latent tuberculous infection (LTBI), as recommended by the Brazilian Society of Rheumatology.5 None of them had any significant AE that could determine the switching of any medication. Of the 39 patients undergoing switching between anti-TNF-alpha agents, none used isoniazid again, since no reinvestigation for LTBI was conducted prior to the introduction of the second TNF-alpha inhibitor. Thus, no association was observed between the use of isoniazid, either in the first or second time, and the AEs causing the switching between agents. However, for one patient, the switching strategy was used due to professional epidemiology (the patient is a community health agent of the Family Health Program).
The most frequently used first anti-TNF-alpha agent was IFX, followed by ETN and ADA at the same proportion (Table 2). However, most patients (69.6%) required an IFX dose increase or infusion interval reduction, to maintain the clinical benefit over time. The mean length of use of the first anti-TNF-alpha agent, prior to switching, was 14.6 ± 10.7 months. In that period, a significant decrease in DAS28 and an improvement in the functional capacity were observed (Table 3).
Switching between monoclonal antibodies occurred in 43.2% of the patients. In almost 40% (n = 14) of the sample, switching was from monoclonal antibodies (IFX or ADA) to soluble TNF-alpha receptor (ETN). Seven patients (18.9%) switched from the soluble receptor to monoclonal antibodies. Thus, as second anti-TNF-alpha agent, 21 patients (56.8%) used ADA, 14 (37.8%) used ETN, and only two (5.4%) used IFX (Figure 1).
Regarding the reasons for switching the first anti-TNF-alpha agent, nine patients (24.3%) had PF, 13 (35.2%) had SF, and 15 (40.5%) had AE. The major AEs motivating the switch were as follows: infusion reaction (n = 4); urticaria (n = 7); respiratory infection (n ; = 1); and other causes (n = 3), such as upper gastrointestinal hemorrhage and strong epidemiology for LTBI (professional contact with bacillus-carrying patients) (Figure 2). Among those switching agents due to AEs, the mean length of use of the first anti-TNF-alpha agent was 9.3 ± 6.9 months, and the mean DAS28 before and after the first anti-TNF-alpha agent were 5.9 ± 1.2 and 4.6 ± 1.1, respectively. More than half of them (54.5%) had achieved a good EULAR response, while 18.2% obtained a moderate response, and 27.3% no response. In the first 24 weeks after switching, no relevant AE was observed, even in those patients who had switched due to toxicity to the first agent.
After switching to the second anti-TNF-alpha agent, disease activity tended to improve, but at a lower magnitude than that of the first agent, according to the reduction in DAS28, but not in functional capacity (Table 3). However, using the definition of the EULAR response, 43.6% (n = 17) of the patients achieved good to moderate response after the introduction of the second anti-TNF-alpha agent, although only two (5.4%) went into clinical remission. In isolation, ESR was not a good parameter to assess the short-term laboratory response.
Only two (5.4%) patients switched the class of medication after using the second anti-TNF-alpha agent. For both, rituximab was used due to PF. None of the patients used a third anti-TNF-alpha agent.
After 24 weeks, when classifying patients according to the final DAS28 into low, and moderate/high activity, the first group had a significantly lower HAQ than that of the second group (Table 4), and also received lower doses of glucocorticoids (GC) and MTX, regardless of age, duration of disease, presence of rheumatoid factor, and erosions on radiography.
Such aspects might characterize disease with better outcome and prognosis (P < 0.05).
On univariate linear analysis, age, duration of disease, and erosive disease did not significantly influence the clinical response to the second anti-TNF-alpha agent. In the final model of logistic regression for low disease activity (DAS28 between 2.61 and 3.2) and good/moderate EULAR response, none of the variables studied were significant enough to explain patients' improvement, except for a tendency towards the lowest value of the initial DAS (OR = 0.15; 95% CI: 0.02-1.26; P = 0.08). Thus, for each unit increase in the initial DAS28, there was a 85% reduction in the chance of having low disease activity after switching the anti-TNF-alpha agent, even after statistical adjustments for age, duration of disease, rheumatoid factor, initial HAQ, erosions, prednisone, MTX, anti-TNF-alpha agent, or reason for switching. The final logistic regression model for remission (DAS28 < 2.6) was not performed, because of the small number of patients.
Our results showed that the switching strategy between anti- TNF-alpha agents was performed in 39% of the patients. That frequency is slightly higher than that reported by other authors, mainly those data originating from studies of registries, in which 25%-40% of the patients discontinue treatment in the first 12 months due to loss of efficacy or AEs.1-3,11-13 It is worth emphasizing that the long duration of disease and the high prevalence of individuals with erosive disease, although with moderate physical incapacity, characterized this cohort. Such aspects can explain the higher prevalence of that strategy.
Usually, some aspects should be considered for decision making and choosing the first or second anti-TNF-alpha agent (Chart 1). Several causes can justify switching between anti-TNF-alpha agents of the same class or with a similar mechanism of action; however, usually the failure in responding (PF or SF) and the AEs are the major causes in most clinical studies published.1,2
Similarly to the present study, Marchesoni et al.,13 in a large cohort of patients on anti-TNF-alpha therapy, have reported that of the 1,064 individuals assessed, 38.1% discontinued the medication. Of those, 44.4% discontinued due to inefficacy, 47.9% due to AEs, and 2.5% due to disease remission. After 36 months, ETN had the best drug survival rate (62.5%) as compared with IFX (49.1%) and ADA (53.2%). The greatest risk of discontinuing therapy due to some AE was associated with advanced age and current use of GC; while the loss of efficacy was associated with previous use of more than three DMARDs and higher ESR.13
In 40.5% of our patients, the reason for switching the anti- TNF-alpha agent was the presence of an AE. Usually, high retention rate of the second anti-TNF-alpha agent is observed in the first year (50%70%), and switching from one anti-TNFalpha agent to another can elicit an adequate clinical response, especially if caused by toxicity, as shown in a recent systematic review that assessed approximately six thousand patients.3 A similar finding has already been reported by Hyrich et al.,12 who, assessing patients switching the first anti-TNF-alpha agent (503 due to inefficacy and 353 due to toxicity), have shown high response and maintenance rates with the second anti-TNF-alpha agent (73%), especially when the switch was motivated by toxicity.12 Of our 15 patients (40.5%) having AEs, five (33%) obtained a good/moderate EULAR response after the switch. Six (27.2%) of those discontinuing the use of the first anti-TNF-alpha agent due to inadequate response (59.5%) had good/moderate EULAR response. Thus, according to such data, clinical response to the second anti-TNF-alpha agent did not depend on the reason for switching (mean of 30%). In addition, toxicity of the second agent was not observed in the first 24 weeks, even in patients with severe AEs resulting from the first anti-TNF-alpha agent. It is worth emphasizing once more that anti-TNF-alpha agents are different, and switching between them is an important strategy in the clinical management of those patients.
Compared to ours, Navarro-Sarabia et al.14 have reported a lower rate of switching to the second anti-TNF-alpha agent (19.9%), but similar frequency of good/moderate EULAR response (47%) and reasons for switching. Almost half of their patients assessed showed improvement of the HAQ (over 0.22) with the second anti-TNF-alpha agent,14 while only 35% of our sample achieved that response. Caporali et al.,15 assessing the data of the Italian registry of the anti-TNF-alpha agents,have also reported a lower switching rate (21.3%) than ours, especially due to PF (36.3%). Slightly more than 47% have achieved a good/moderate EULAR response after six months, and 58.6% after 12 months. Patients with high disease activity and those switching due to loss of efficacy had a greater chance to respond to the second agent.15
Almost 45% of our patients switched between monoclonal antibodies, a strategy less used than that including the soluble TNF-alpha receptor. Burmester et al.16 have shown a high rate of good clinical response after 12 weeks in 358 patients who had switched from IFX to ADA, with 20% improvement in the American College of Rheumatology criteria (ACR20) in 63% of the patients, and 50/70% improvement in the ACR criteria (ACR50/70) in 35% and 12%, respectively.16 For a longer time (six months), but with a smaller number of patients (n = 27), Wick et al.17 have reported a similar response with the same strategy of switching between anti-TNF-alpha agents, shown as a significant reduction in DAS28 values and proportion of individuals achieving ACR20, even when compared with a third group of ADA-naïve.17 A similar study with similar findings, during 12 months, has been published by Nikas et al.18 and Van der Bijl et al.19
Switching from monoclonal antibodies to the soluble TNFalpha receptor was performed in 37.8% of our patients. The clinical response, according to the ACR criteria, has been studied by Haraoui et al.20 in patients with RA who had switched from IFX to ETN due to lack of efficacy or AE. ACR20/50/70 response was observed in 64%, 23%, and 5% of the patients, respectively.20 Buch et al.21 have switched from IFX to ETN, and, after 12 weeks, they have reported good/moderate EULAR response in 73% of the patients. It is worth noting that none of the patients who had discontinued IFX due to toxicity experienced AEs due to ETN.21 Similar findings have also been reported by other authors.22-24
Almost 20% of our patients switched from the soluble TNFalpha receptor to monoclonal antibodies. Regarding the switch from the soluble TNF-alpha receptor to monoclonal antibodies, Gomes-Reino et al.,11 assessing data from the Spanish registry, have reported that 52 patients on ETN switched to IFX, and 14 to ADA. After 12 months, those authors have found a higher drug continuity rate with the same agent in those patients who had switched to ADA (75%) as compared with those who had switched to IFX (28%, of whom 54% discontinued due to AEs).11 Wick et al.17 have studied switching from ETN to ADA, with a significant reduction in the DAS28. With the same strategy and a larger sample, but with only three months of follow-up, Burmester et al.16 have observed the ACR20/50/70 response at the proportion of 52/30/11, respectively. Scrivo etal.2 have also assessed the response to ADA of patients who had used ETN. After three months, 64% of the patients showed an adequate EULAR response, but almost 40% failed to respond.2 Although with few patients, Furst et al.,25 van Vollenhoven et al.,26 Hansen et al.,27 and Cohen et al.28 have reported similar findings
The major risk factors associated with switching between anti-TNF-alpha agents are the traditional risk factors of worse prognosis, such as poor response to DMARDs, greater number of swollen joints, longer disease duration, greater degree of disability, and persistently elevated inflammatory activity tests. Although the literature is still controversial, the presence of HACAs or HAHAs seems to be related to immuno-allergic and infusion reactions rather than to loss ofefficacy.29 In our study, only the higher disease activity, measured by DAS28, associated with worse clinical response after the switching strategy, independently of disease duration, age, physical disability, rheumatoid factor, and erosions on radiography.
More recently, Rémy et al.,30 in a systematic review of the literature with subsequent meta-analysis of 32 relevant studies and inclusion of 4,441 patients, have shown good clinical relevance of the switching strategy between anti-TNF-alpha agents. ACR20 and EULAR responses were observed in 55.1% and 74.9% of the patients, respectively, a finding very similar to those of pivotal studies with anti-TNF-alpha-naïve individuals. Once again, the authors have confirmed previous results, in which switching due to inadequate response was associated with lower ACR20 response (54.3%) vs. switching due to AEs (62,5%). However, no significant difference was observed when that outcome was statistically assessed by use of EULAR response.30
Most published studies on the switching strategy to the second anti-TNF-alpha agent have assessed parameters related to improvement in clinical activity,12,15-17,20,21,31 but not to other outcomes, such as the functional ones, remission, quality oflife, and structural damage on radiography. This study, however, assesses functional capacity and remission as primary outcomes. Considering the new remission criteria recently proposed by ACR/EULAR [SDAI < 3.3, or tender and swollen joint counts, patient's global assessment, and C-reactive protein < 1],32 none of our patients would meet these criteria.
Our study has some limitations, such as the retrospective design and its inherent problems, and the relatively reduced number of patients in each subgroup, after stratifying according to the reason for switching. Therefore, assessing the response effectiveness in each clinical setting was not possible. However, our study has some strong points, such as the low loss to follow-up rate and the functional capacity assessment, an outcome rarely reported in most studies. It is worth noting that, although patients had a long disease duration, they had moderate physical disability (mean HAQ < 1.5, and functional class II and III), which neither causes selection bias nor hinders the finding. Moreover, it draws attention to the greater weekly dose of MTX and greater frequency of leflunomide users, differently from that reported in the international literature.3,11,26,33 The lack of bias of concomitant medication strengthens the role of immunobiologic agents, since the doses and type of combination of synthetic DMARCs were maintained stable for 24 weeks after switching between anti-TNF-alpha agents.
Thus, our data suggest that switching between anti-TNFalpha agents is a valid strategy for the clinical management of patients with RA, particularly using the improvement criteria proposed by EULAR, although with low probability of remission and no significant improvement in functional capacity. However, further clinical studies, especially prospective, randomized and controlled ones, and with larger samples, are required to define the best way to manage those patients. Such studies should include the demonstration of structural benefit, gain in quality of life, and missed work days.
1Keystone EC. Switching tumor necrosis factor inhibitors: an opinion. Nat Clin Pract Rheumatol 2006;2(11):576- 7.
2Scrivo R, Conti F, Spinelli FR, Truglia S, Magrini L, Di Franco M et al Switching between TNFα antagonists in rheumatoid arthritis: personal experience and review of the literature. Reumatismo 2009; 61(2):107-17.
3Carmona L, Ortiz A, Abad MA. How good is to switch between biologics? A systematic review of the literature. Acta Reumatol Port 2007;2(2):113- 28.
4Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS et al The American Rheumatism Association 1987 revised criteria for classification of rheumatoid arthritis. Arthritis Rheum 1988;31(3):315- 24.
5Bértolo MB, Brenol CV, Schainberg CG, Neubarth F, Lima FAC, Laurindo IM et al Atualização do consenso brasileiro no diagnóstico e tratamento da artrite reumatoide. Rev Bras Reumatol 2007;47(3):151- 9.
6Hochberg MC, Chang RW, Dwosh I, Lindsey S, Pincus T, Wolf F. The American College of Rheumatology 1991 revised criteria for the classification for global functional status in rheumatoid arthritis. Arthritis Rheum 1992;35(5):498- 502.
7van Gestel AM, Prevoo ML, van't Hof MA, van Rijswijk MH, van de Putte LB, van Riel PL. Development and validation of the European League Against Rheumatism response criteria for rheumatoid arthritis. Comparison with the preliminary American College of Rheumatology and the World Health Organization/International League Against Rheumatism criteria. Arthritis Rheum 1996;39(1):34-40.
8The tripartite core harmonized ICH guideline. Available from: http://www.ich.org/cache/compo/475-272-1.html Accessed on October 2010.
9Ferraz MB, Oliveira LM, Araujo PM, Atra E, Tugwell P. Crosscultural reliability of the physical ability dimension of the health assessment questionnaire. J Rheumatol 1990;17(6):813- 7.
10Prevoo ML, van't Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL. Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 1995;38(1):44-8.
11Gomez-Reino JJ, Carmona L; BIOBADASER group. Switching TNF antagonists in patients with chronic arthritis: an observational study of 488 patients over a four-year period. Arthritis Res Ther 2006;8(1):R29.
12Hyrich KL, Lunt M, Watson KD, Symmons DP, Silman AJ. British Society for Rheumatology Biologics Register. 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 2007;56(1):13-20.
13Marchesoni A, Zaccara E, Gorla R, Bazzani C, Sarzi-Puttini P, Atzeni F et al TNF-alpha antagonist survival rate in a cohort of rheumatoid arthritis patients observed under conditions of standard clinical practice. Ann N Y Acad Sci 2009;1173:837-46.
14Navarro-Sarabia F, Ruiz-Montesinos D, Hernandez B, Navarro-Compán V, Marsal S, Barcelo M et al DAS-28-based EULAR response and HAQ improvement in rheumatoid arthritis patients switching between TNF antagonists. BMC Musculoskelet Disord 2009;10:91.
15Caporali R, Sarzi-Puttini P, Atzeni F, Gorla R, Filippini M, Marchesoni A et al Switching TNF-alpha antagonists in rheumatoid arthritis: the experience of the LORHEN registry. Autoimmun Rev 2010;9(6):465-9.
16Burmester GR, Monteagudo Saez I, Malaise MG, Canas da Silva J, Webber DG, Kupper H. Adalimumab (Humira®) is effective in patients who previously have been treated with TNF-antagonist (etanercept and/or infliximab) in widespread clinical practice: 12-week outcomes in the REACT trial. Ann Rheum Dis 2005;64:(Suppl. III):423.
17Wick MC, Ernestam S, Lindblad S, Bratt J, Klareskog L, von Vollenhoven RF. Adalimumab (Humira) restores clinical response in patients with secondary loss of efficacy from infliximab (Remicade) or etanercepte (Enbrel): results from the STURE registry at Karolinska University Hospital. Scand J Rheumatol 2005;34(5):353- 8.
18Nikas SN, Voulgari PV, Alamanos Y, Papadopoulos CG, Venetsanopoulou AI, Georgiadis AN et al Efficacy and safety of switching from infliximab to adalimumab: a comparative controlled study. Ann Rheum Dis 2006;65(2):257-60.
19van der Bijl AE, Breedveld FC, Antoni CE, Kalden JR, Kary S, Burmester GR et al An open-label pilot study of the effectiveness of adalimumab in patients with rheumatoid arthritis and previous infliximab treatment: relationship to reasons for failure and antiinfliximab antibody status. Clin Rheumatol 2008;27(8):1021-8.
20Haraoui B, Keystone EC, Thorne C, Pope JE, Chen I, Asare CG et al Clinical outcomes of patients with rheumatoid arthritis after switching from infliximab to etanercept. J Rheumatol 2004;31(12):2356-9.
21Buch MH, Bingham SJ, Bejarano V, Bryer D, White J, Reece R et al Therapy of patients with rheumatoid arthritis: outcome of infliximab failures switched to etanercept. Arthritis Rheum 2007;57(3):448-53.
22Di Poi E, Perin A, Morassi MP, Del Frate M, Ferraccioli GF, De Vita S. Switching to etanercept in patients with rheumatoid arthritis with no response to infliximab. Clin Exp Rheumatol 2007;25(1):85-7.
23Ianone F, Trotta F, Monteccuco C, Giacomelli R, Galeazzi M, Matucci-Cerinic M et al; GISEA (Gruppo Italiano per lo Studio delle Early Arthritis). Etanercept maintains the clinical benefitachieved by infliximab in patients with rheumatoid arthritis who discontinued infliximab because of side effects. Ann Rheum Dis 2007;66(2):249-52.
24Laas K, Peltomaa R, Kautiainen H, Leirisalo-Repo M. Clinical impact of switching from infliximab to etanercept in patients with rheumatoid arthritis. Clin Rheumatol 2008;27(7):927-32.
25Furst DE, Gaylis N, Bray V, Olech E, Yocum D, Ritter J et al Openlabel, pilot protocol of patients with rheumatoid arthritis who switch to infliximab after an incomplete response to etanercept: the opposite study. Ann Rheum Dis 2007;66(7):893-9.
26van Vollenhoven R, Harju A, Brannemark S, Klareskog L. Treatment vice-versa: data from the STURE registry showing that switching tumour necrosis factor alpha blockers can make sense. Ann Rheum Dis 2003;62(12):1195-8.
27Hansen KE, Hildebrand JP, Genovese MC, Cush JJ, Patel S, Cooley DA et al The efficacy of switching from etanercept to infliximab in patients with rheumatoid arthritis. J Rheumatol 2004;31(6):1098-102.
28Cohen G, Courvoisier N, Cohen JD, Zaltni S, Sany J, Combe B. The efficiency of switching from infliximab to etanercept and vice-versa in patients with rheumatoid arthritis. Clin Exp Rheumatol 2005;23(6):795- 800.
29Bartelds GM, Wijbrandts CA, Nurmohamed MT, Stapel S, Lems WF, Aarden L et al Anti-infliximab and anti-adalimumab antibodies in relation to response to adalimumab in infliximab switchers and antitumour necrosis factor naïve patients: a cohort study. Ann Rheum Dis 2010;69(5):817-21.
30Rémy A, Avouac J, Gossec L, Combe B. Clinical relevance of switching to a second tumour necrosis factor alpha inhibitor after discontinuation of a first tumour necrosis factor-alpha inhibitor in rheumatoid arthritis: a systematic literature review and metaanalysis. Clin Exp Rheumatol 2011;29(1):96-103. Epub 2011 Feb 23.
31Lloyd S, Bujkiewicz S, Wailoo AJ, Sutton AJ, Scott D. The effectiveness of anti-TNF-alpha therapies when used sequentially in rheumatoid arthritis patients: a systematic review and meta-analysis. Rheumatology (Oxford) 2010;49(12):2313-21.
32Felson DT, Smolen JS, Wells G, Zhang B, van Tuyl LH, Funovits J et al American College of Rheumatology; European League Against Rheumatism. American College of Rheumatology/European League Against Rheumatism provisional definition of remission in rheumatoid arthritis for clinical trials. Arthritis Rheum 2011;63(3):573-86.
33Hyrich KL, Lunt M, Dixon WG, Watson KD, Symmons DP, BSR Biologics Register. Effects of switching between anti-TNF therapies on HAQ response in patients who do not respond to their first anti-TNF drug. Rheumatology (Oxford) 2008;47(7):1000-5.
Switching between anti-TNF-alpha agents does not improve functional capacity in patients with long-standing and active rheumatoid arthritis
Publication in this collection
26 Jan 2012
Date of issue
03 Feb 2011
02 Nov 2011