PRIORITY PAPER EVALUATION For reprint orders, please contact: [email protected]
Comparative effectiveness of biologic antirheumatic therapies in rheumatoid arthritis after failure to respond to a first TNF inhibitor Evaluation of: Gomez-Reino JJ, Maneiro JR, Ruiz J et al. Comparative effectiveness of switching to alternative tumour necrosis factor (TNF) antagonists versus switching to rituximab in patients with rheumatoid arthritis who failed previous TNF antagonists: the MIRAR Study. Ann. Rheum. Dis. doi:10.1136/annrheumdis-2012-201324 (2012) (Epub ahead of print). Rheumatoid arthritis is a chronic immune-mediated disease affecting approximately 1% of the population. The prognosis of this chronic condition has considerably improved over the past decade with the earlier use of antirheumatic drugs and the introduction of new biologic therapies. Current treatment guidelines recommend using these agents after a failed response to conventional disease-modifying antirheumatic drugs, but the relative positioning of the various available biologic agents is not yet well established. All biologic agents have been proven to be superior to placebo in large trials, but only very few randomized controlled trials have compared directly competing therapeutic options. This article evaluates the effectiveness of rituximab compared with an alternative TNF antagonist (anti-TNF) in rheumatoid arthritis patients who experienced a previous failed response to anti-TNF. The results of this large observational cohort study suggest that rituximab offers a greater benefit on rheumatoid arthritis disease activity than alternative monoclonal anti-TNFs.
Axel Finckh Division of Rheumatology, University Hospital of Geneva, Switzerland and Division of Clinical Epidemiology, University of Geneva, 26 Av. Beau-Sejour, 1211 Geneva 14, Switzerland Tel.: +41 22 382 3693 Fax: +41 22 382 3535 [email protected]
Keywords: antirheumatic therapy n B-cell depleting therapy n rheumatoid arthritis n rituximab n TNF-a inhibitors
Rheumatoid arthritis (RA) is a chronic immune-mediated disease characterized by progressive joint destruction, extra-articular manifestations and permanent disability. RA is the most prevalent systemic rheumatic disease affecting approximately 1% of the adult population. Its relatively early onset in life implies that it affects working-age populations, resulting in work disability rates increasing by ten-times, with considerable indirect costs due to lost productivity [1]. The pervasive consequences of the disease have led the WHO to classify RA as one of the ten leading causes of disease burden in women [2]. Until recently, RA was viewed as an inexorably progressive disease, but it now appears that we are able to change the course of the disease by treating it earlier and using more aggressive therapies. Among these are the so-called ‘biologic antirheumatic drugs’ (biologics), which have demonstrated superior efficacy against structural joint damage. At this time, five TNF antagonists (anti-TNFs) and several other biologic agents, with different mechanisms of action are on the market. Among the biologics with a different mode of action are agents targeting specific immune cells (CD20+ B lymphocytes and rituximab [RTX]), anticytokines (IL-6 and tocilizumab) and inhibitors of T-cell costimulation (abatacept). All biologic antirheumatic agents have been demonstrated to be superior to placebo in randomized controlled trials (RCTs) but only one published trial has directly compared two biologic options [3]. Thus, the relative positioning of these biologic
10.2217/CER.12.50 © 2012 Future Medicine Ltd
1(6), 481–484 (2012)
part of
ISSN 2042-6305
481
PRIORITY PAPER EVALUATION Finckh
482
agents is not yet well determined and the most rational therapeutic approach for patients with aggressive RA is still unclear [4]. Anti-TNFs are the first and by far the most widely used biologic agents in RA, but not all patients respond adequately to this therapy. Until recently, options were limited for patients experiencing an inadequate response to this class of medication and it was common practice to switch to an alternative anti-TNF agent, despite limited evidence. With the growing availability of biologics with a different mode of action, patients with an unsatisfactory response to antiTNFs started to be switched to the newer agents to overcome drawbacks related to class [5]. We will briefly discuss a recent study comparing the effectiveness of RTX with that of alternative anti-TNFs in RA patients who experienced a previous failure to respond to anti-TNF [6].
were largely corrected after propensity score stratification. Overall, the study did not demonstrate a significant difference in DAS28 and HAQ improvement over time between RTX and the alternative anti-TNFs. However, the relative benefit of switching to RTX was different in particular patient subgroups. Switching to RTX was significantly more effective than switching to monoclonal anti-TNF antibodies (mean DAS28 improvement 1.61 vs 1.04; p = 0.001), while the difference between RTX and etanercept did not reach significance (mean DAS28 improvement 1.61 vs 1.32; p = 0.19). When the primary end points were dichotomized into predefined responder categories, the response rates on RTX tended to be higher than on alternative anti-TNFs (good EULAR response, p = 0.03; HAQ improvement of >0.22, p = 0.06).
Methods & results
Discussion
This paper is an observational cohort study of Spanish RA patients who received either RTX or an alternative anti-TNF (adalimumab, etanercept or infliximab) after failing to respond to an anti-TNF in routine clinical practice. Patients were included at the time of treatment switch (baseline) and assessed at approximately at 6, 9 and 12 months. The primary outcomes were RA disease activity, as measured by the Disease Activity Score based on 28 joints (DAS28), and functional disability based on the Health Assessment Questionnaire (HAQ). The change in outcomes over time was analyzed using multivariate regression models for longitudinal data. To correct for potential biases due to nonrandom treatment allocation, the authors used propensity score stratification. The paper further examined potential effect modification by the type of anti-TNF switch (etanercept vs monoclonal antibodies: adalimumab or infliximab). A total of 1124 RA patients were enrolled after discontinuing at least one anti-TNF. Approximately half of the patients subsequently received RTX (53%) and the other half an alternative anti-TNF (47%). The two groups were balanced for gender, age and rheumatoid factor positivity, but differed for measures of disease severity. Patients in the RTX cohort had longer disease durations, more extra-articular RA manifestations, failed treatment with more prior anti-TNFs and conventional antirheumatic agents, and had higher levels of disease activity at baseline. These baseline differences
In the absence of large head-to-head RCTs directly comparing two therapeutic options, several observational studies have analyzed the same question in an observational setting [7–13]. On average, these analyses showed a difference between 0.4 and 0.8 DAS28 units in favor of RTX compared with an alternative anti-TNF, corroborating the results found in this analysis. This corresponds to a clinically significant difference, as confirmed by a benefit in patient’s self-assessed function (HAQ score). One conclusion of the available evidence is that a switch to biologic agents with a different mode of action should be considered for patients who have not responded adequately to anti-TNFs. A likely explanation for these findings may be linked with the particular immune mechanisms that drive the inflammation in patients failing anti-TNFs and class issues related to anti-TNF agents. Effectiveness analyses in an observational setting share common methodological challenges, whether from registries or from administrative databases [14]. Selection bias is the key limitation when using observational data to analyze effectiveness. Selection bias occurs when disease characteristics lead to a particular treatment, but are also associated with disease outcome. Some degree of selection is apparent in this paper, as most patients on RTX appear to have had more severe disease at the time of the switch. Another limitation of observational data is confounding, which occurs whenever the treatment effect is muddled up with the effects of unrelated factors.
J. Compar. Effect. Res. (2012) 1(6)
future science group
Biologic antirheumatic therapies in rheumatoid arthritis
The authors of this attempted to correct for confounding by using propensity score stratification, which removes most of the bias related to the factors included into the propensity score, but does not resolve issues of unmeasured confounding or residual confounding. While a direct comparison of the efficacy of these two agents in a randomized controlled trial would be more compelling, it is reassuring that all published observational comparative effectiveness analyses have generated compatible results [7–13]. One of the interesting aspects of GomezReino’s paper is that it identifies a particular subgroup of patients for whom switching to a biologic agent with a different mechanism of action makes most sense. In particular, their results suggest that switching between monoclonal antibody anti-TNF agents is less effective than switching to RTX; while switching to etanercept, a soluble receptor of TNF, might still offer reasonable response rates. Other comparative effectiveness analyses have identified different subgroups: in the Swiss cohort, the reason for discontinuing the previous anti-TNF influenced the relative benefit of subsequent biologics; only the patients switching for ineffectiveness responded significantly better to RTX than to an alternative antiTNF [8]. In a German cohort, the relative benefit of RTX was significantly larger in ‘seropositive’ (rheumatoid factor postive or anti-CCP positive) RA patients [9]. Overall, this illustrates another interesting aspect of comparative effectiveness
PRIORITY PAPER EVALUATION
research, which is to identify particular patient subgroups who are more likely to respond to a drug [14]. Future perspective
Different study designs have been used to conduct comparative effectiveness research, including RCTs, indirect comparisons using metaanalysis and observational studies. In RA, most comparative research has been observational, as the vast majority of RCTs have been against placebo, which is of limited value for clinical practice and does not allow a comparison of antirheumatic treatments. Recently, however, several RCTs against true therapeutic comparators are being conducted in RA [15,16,101,102], which will hopefully confirm the findings from observational analyses and help clinicians to appraise the benefits and potential harms of biotherapies in RA. Financial & competing interests disclosure A Finckh is supported by a research grant from the Swiss National Science Foundation (Grant N° 3200B0120639). He has also given talks for Roche Pharma, Abbott, MSD and Pfizer. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.
Executive summary In patients with rheumatoid arthritis who failed to respond to a previous TNF antagonist (anti-TNF), switching to rituximab was significantly more effective than switching to alternative monoclonal antibody anti-TNFs (adalimumab or infliximab). ■■ The available evidence suggests that a switch to a biologic agent with a different mode of action should be considered for patients who have not responded adequately to anti-TNFs previously. ■■
References 1
Felts W, Yelin E. The economic impact of the rheumatic diseases in the United States. J. Rheumatol. 16, 867–884 (1989)
2
Fighting disease, fostering development, The WHO Report (1996).
3
Schiff M, Keiserman M, Codding C et al. Efficacy and safety of abatacept or infliximab vs placebo in ATTEST: a Phase III, multi-centre, randomised, double-blind, placebo-controlled study in patients with rheumatoid arthritis and an inadequate response to methotrexate. Ann. Rheum. Dis. 67, 1096–1103 (2008).
4
A plethora of treatment options for rheumatoid arthritis, but critical trial design issues. Arthritis Rheum. 56, 3884–3886 (2007).
O’Dell JR. It is the best of times; it is the worst of times: is there a way forward?
future science group
5
Rubbert-Roth A, Finckh A. Treatment options in patients with rheumatoid arthritis failing initial TNF inhibitor therapy: a critical review. Arthritis Res. Ther. 11(Suppl.1), S1 (2009).
6
Gomez-Reino JJ, Maneiro JR, Ruiz J et al. Comparative effectiveness of switching to alternative tumour necrosis factor (TNF) antagonists versus switching to rituximab in patients with rheumatoid arthritis who failed previous TNF antagonists: the MIRAR Study. Ann. Rheum. Dis. doi:10.1136/
www.futuremedicine.com
annrheumdis-2012-201324 (2012) (Epub ahead of print). 7
Finckh A, Ciurea A, Brulhart L et al. B cell depletion may be more effective than switching to an alternative anti-tumor necrosis factor agent in rheumatoid arthritis patients with inadequate response to anti-tumor necrosis factor agents. Arthritis Rheum. 56, 1417–1423 (2007).
8
Finckh A, Ciurea A, Brulhart L et al. Which subgroup of patients with rheumatoid arthritis benefits from switching to rituximab versus alternative anti-tumour necrosis factor (TNF) agents after previous failure of an anti-TNF agent? Ann. Rheum. Dis. 69, 387–393 (2010).
483
PRIORITY PAPER EVALUATION Finckh 9
Kekow J, Mueller-Ladner U, Schulze-Koops H. Rituximab is more effective than second anti-TNF therapy in rheumatoid arthritis patients and previous TNFa blocker failure. Biologics 6, 191–199 (2012).
10
Blom M, Kievit W, Donders AR et al. Effectiveness of a third tumor necrosis factor- a-blocking agent compared with rituximab after failure of 2 TNF-blocking agents in rheumatoid arthritis. J. Rheumatol. 38, 2355–2361 (2011).
11 Moetaza M, Hyrich K, Lunt M et al.
Rituximab or a second anti-tumor necrosis factor therapy for rheumatoid arthritis patients who have failed their first anti-tumor necrosis factor therapy? Comparative analysis from the british society for rheumatology biologics register. Arthritis Care Res. 64, 1108–1115 (2012). 12 Emery P, Gottenberg J, Sarzi-Puttini P et al.
Relative effectiveness of rituximab versus an alternative TNF inhibitor in patients with
484
rheumatoid arthritis and an inadequate response to a single previous TNF inhibitor: results from SWITCH-RA, a global, comparative-effectiveness, observational study. Arthritis Rheum 63(Suppl. 10), 126 (2011). 13 Rituximab versus anti-TNF in RA patients
who previously failed one TNF inhibitor in an observational cohort. Scand. J. Rheum. (2012) (In Press). 14
Finckh A. Comparative effectiveness of rheumatoid arthritis therapies. Curr. Rheum. Rep. 12, 348–354 (2011).
15 Gabay C, Emery P, van Vollenhoven R et al.
Tocilizumab (TCZ) monotherapy is superior to adalimumab (ADA) monotherapy in reducing disease activity in patients with rheumatoid arthritis (RA): 24-week data from the phase 4 ADACTA trial. Ann. Rheum. Dis. 71(Suppl. 3),152, Abstract LB0003 (2012). 16 Schiff M, Fleischmann R, Weinblatt M et al.
Abatacept SC versus adalimumab on
J. Compar. Effect. Res. (2012) 1(6)
background methotrexate in RA: one year results from the AMPLE study. EULAR Ann. Science Meeting. Ann. Rheum. Dis. 60, OP0022 (2012).
■■ Websites 101 Moreland LW, Genovese MC. National
Institute of Allergy and Infectious Diseases (NIAID): switching anti-TNF- a agents in RA (NCT00796705). Clinicaltrials.gov, NCT00796705 (2008). http://clinicaltrials.gov/ct2/show/NCT00796 705?term=tumour+necrosis+inadequate+resp onse&rank=5 102 Gottenberg J. Rotation or change of
biotherapy after first anti-TNF treatment failure for rheumatoid arthritis (ROC). Clinicaltrials.gov. NCT01000441 (2009). http://clinicaltrials.gov/ct2/show/NCT01000 441?term=rheumatoid+arthritis&type=Intr& cond=rheumatoid+arthritis&intr=rituximab &rank=33
future science group
Comparative effectiveness of biologic antirheumatic therapies in rheumatoid arthritis after failure to respond to a first TNF inhibitor Evaluation of: Gomez-Reino JJ, Maneiro JR, Ruiz J et al. Comparative effectiveness of switching to alternative tumour necrosis factor (TNF) antagonists versus switching to rituximab in patients with rheumatoid arthritis who failed previous TNF antagonists: the MIRAR Study. Ann. Rheum. Dis. doi:10.1136/annrheumdis-2012-201324 (2012) (Epub ahead of print). Rheumatoid arthritis is a chronic immune-mediated disease affecting approximately 1% of the population. The prognosis of this chronic condition has considerably improved over the past decade with the earlier use of antirheumatic drugs and the introduction of new biologic therapies. Current treatment guidelines recommend using these agents after a failed response to conventional disease-modifying antirheumatic drugs, but the relative positioning of the various available biologic agents is not yet well established. All biologic agents have been proven to be superior to placebo in large trials, but only very few randomized controlled trials have compared directly competing therapeutic options. This article evaluates the effectiveness of rituximab compared with an alternative TNF antagonist (anti-TNF) in rheumatoid arthritis patients who experienced a previous failed response to anti-TNF. The results of this large observational cohort study suggest that rituximab offers a greater benefit on rheumatoid arthritis disease activity than alternative monoclonal anti-TNFs.
Axel Finckh Division of Rheumatology, University Hospital of Geneva, Switzerland and Division of Clinical Epidemiology, University of Geneva, 26 Av. Beau-Sejour, 1211 Geneva 14, Switzerland Tel.: +41 22 382 3693 Fax: +41 22 382 3535 [email protected]
Keywords: antirheumatic therapy n B-cell depleting therapy n rheumatoid arthritis n rituximab n TNF-a inhibitors
Rheumatoid arthritis (RA) is a chronic immune-mediated disease characterized by progressive joint destruction, extra-articular manifestations and permanent disability. RA is the most prevalent systemic rheumatic disease affecting approximately 1% of the adult population. Its relatively early onset in life implies that it affects working-age populations, resulting in work disability rates increasing by ten-times, with considerable indirect costs due to lost productivity [1]. The pervasive consequences of the disease have led the WHO to classify RA as one of the ten leading causes of disease burden in women [2]. Until recently, RA was viewed as an inexorably progressive disease, but it now appears that we are able to change the course of the disease by treating it earlier and using more aggressive therapies. Among these are the so-called ‘biologic antirheumatic drugs’ (biologics), which have demonstrated superior efficacy against structural joint damage. At this time, five TNF antagonists (anti-TNFs) and several other biologic agents, with different mechanisms of action are on the market. Among the biologics with a different mode of action are agents targeting specific immune cells (CD20+ B lymphocytes and rituximab [RTX]), anticytokines (IL-6 and tocilizumab) and inhibitors of T-cell costimulation (abatacept). All biologic antirheumatic agents have been demonstrated to be superior to placebo in randomized controlled trials (RCTs) but only one published trial has directly compared two biologic options [3]. Thus, the relative positioning of these biologic
10.2217/CER.12.50 © 2012 Future Medicine Ltd
1(6), 481–484 (2012)
part of
ISSN 2042-6305
481
PRIORITY PAPER EVALUATION Finckh
482
agents is not yet well determined and the most rational therapeutic approach for patients with aggressive RA is still unclear [4]. Anti-TNFs are the first and by far the most widely used biologic agents in RA, but not all patients respond adequately to this therapy. Until recently, options were limited for patients experiencing an inadequate response to this class of medication and it was common practice to switch to an alternative anti-TNF agent, despite limited evidence. With the growing availability of biologics with a different mode of action, patients with an unsatisfactory response to antiTNFs started to be switched to the newer agents to overcome drawbacks related to class [5]. We will briefly discuss a recent study comparing the effectiveness of RTX with that of alternative anti-TNFs in RA patients who experienced a previous failure to respond to anti-TNF [6].
were largely corrected after propensity score stratification. Overall, the study did not demonstrate a significant difference in DAS28 and HAQ improvement over time between RTX and the alternative anti-TNFs. However, the relative benefit of switching to RTX was different in particular patient subgroups. Switching to RTX was significantly more effective than switching to monoclonal anti-TNF antibodies (mean DAS28 improvement 1.61 vs 1.04; p = 0.001), while the difference between RTX and etanercept did not reach significance (mean DAS28 improvement 1.61 vs 1.32; p = 0.19). When the primary end points were dichotomized into predefined responder categories, the response rates on RTX tended to be higher than on alternative anti-TNFs (good EULAR response, p = 0.03; HAQ improvement of >0.22, p = 0.06).
Methods & results
Discussion
This paper is an observational cohort study of Spanish RA patients who received either RTX or an alternative anti-TNF (adalimumab, etanercept or infliximab) after failing to respond to an anti-TNF in routine clinical practice. Patients were included at the time of treatment switch (baseline) and assessed at approximately at 6, 9 and 12 months. The primary outcomes were RA disease activity, as measured by the Disease Activity Score based on 28 joints (DAS28), and functional disability based on the Health Assessment Questionnaire (HAQ). The change in outcomes over time was analyzed using multivariate regression models for longitudinal data. To correct for potential biases due to nonrandom treatment allocation, the authors used propensity score stratification. The paper further examined potential effect modification by the type of anti-TNF switch (etanercept vs monoclonal antibodies: adalimumab or infliximab). A total of 1124 RA patients were enrolled after discontinuing at least one anti-TNF. Approximately half of the patients subsequently received RTX (53%) and the other half an alternative anti-TNF (47%). The two groups were balanced for gender, age and rheumatoid factor positivity, but differed for measures of disease severity. Patients in the RTX cohort had longer disease durations, more extra-articular RA manifestations, failed treatment with more prior anti-TNFs and conventional antirheumatic agents, and had higher levels of disease activity at baseline. These baseline differences
In the absence of large head-to-head RCTs directly comparing two therapeutic options, several observational studies have analyzed the same question in an observational setting [7–13]. On average, these analyses showed a difference between 0.4 and 0.8 DAS28 units in favor of RTX compared with an alternative anti-TNF, corroborating the results found in this analysis. This corresponds to a clinically significant difference, as confirmed by a benefit in patient’s self-assessed function (HAQ score). One conclusion of the available evidence is that a switch to biologic agents with a different mode of action should be considered for patients who have not responded adequately to anti-TNFs. A likely explanation for these findings may be linked with the particular immune mechanisms that drive the inflammation in patients failing anti-TNFs and class issues related to anti-TNF agents. Effectiveness analyses in an observational setting share common methodological challenges, whether from registries or from administrative databases [14]. Selection bias is the key limitation when using observational data to analyze effectiveness. Selection bias occurs when disease characteristics lead to a particular treatment, but are also associated with disease outcome. Some degree of selection is apparent in this paper, as most patients on RTX appear to have had more severe disease at the time of the switch. Another limitation of observational data is confounding, which occurs whenever the treatment effect is muddled up with the effects of unrelated factors.
J. Compar. Effect. Res. (2012) 1(6)
future science group
Biologic antirheumatic therapies in rheumatoid arthritis
The authors of this attempted to correct for confounding by using propensity score stratification, which removes most of the bias related to the factors included into the propensity score, but does not resolve issues of unmeasured confounding or residual confounding. While a direct comparison of the efficacy of these two agents in a randomized controlled trial would be more compelling, it is reassuring that all published observational comparative effectiveness analyses have generated compatible results [7–13]. One of the interesting aspects of GomezReino’s paper is that it identifies a particular subgroup of patients for whom switching to a biologic agent with a different mechanism of action makes most sense. In particular, their results suggest that switching between monoclonal antibody anti-TNF agents is less effective than switching to RTX; while switching to etanercept, a soluble receptor of TNF, might still offer reasonable response rates. Other comparative effectiveness analyses have identified different subgroups: in the Swiss cohort, the reason for discontinuing the previous anti-TNF influenced the relative benefit of subsequent biologics; only the patients switching for ineffectiveness responded significantly better to RTX than to an alternative antiTNF [8]. In a German cohort, the relative benefit of RTX was significantly larger in ‘seropositive’ (rheumatoid factor postive or anti-CCP positive) RA patients [9]. Overall, this illustrates another interesting aspect of comparative effectiveness
PRIORITY PAPER EVALUATION
research, which is to identify particular patient subgroups who are more likely to respond to a drug [14]. Future perspective
Different study designs have been used to conduct comparative effectiveness research, including RCTs, indirect comparisons using metaanalysis and observational studies. In RA, most comparative research has been observational, as the vast majority of RCTs have been against placebo, which is of limited value for clinical practice and does not allow a comparison of antirheumatic treatments. Recently, however, several RCTs against true therapeutic comparators are being conducted in RA [15,16,101,102], which will hopefully confirm the findings from observational analyses and help clinicians to appraise the benefits and potential harms of biotherapies in RA. Financial & competing interests disclosure A Finckh is supported by a research grant from the Swiss National Science Foundation (Grant N° 3200B0120639). He has also given talks for Roche Pharma, Abbott, MSD and Pfizer. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.
Executive summary In patients with rheumatoid arthritis who failed to respond to a previous TNF antagonist (anti-TNF), switching to rituximab was significantly more effective than switching to alternative monoclonal antibody anti-TNFs (adalimumab or infliximab). ■■ The available evidence suggests that a switch to a biologic agent with a different mode of action should be considered for patients who have not responded adequately to anti-TNFs previously. ■■
References 1
Felts W, Yelin E. The economic impact of the rheumatic diseases in the United States. J. Rheumatol. 16, 867–884 (1989)
2
Fighting disease, fostering development, The WHO Report (1996).
3
Schiff M, Keiserman M, Codding C et al. Efficacy and safety of abatacept or infliximab vs placebo in ATTEST: a Phase III, multi-centre, randomised, double-blind, placebo-controlled study in patients with rheumatoid arthritis and an inadequate response to methotrexate. Ann. Rheum. Dis. 67, 1096–1103 (2008).
4
A plethora of treatment options for rheumatoid arthritis, but critical trial design issues. Arthritis Rheum. 56, 3884–3886 (2007).
O’Dell JR. It is the best of times; it is the worst of times: is there a way forward?
future science group
5
Rubbert-Roth A, Finckh A. Treatment options in patients with rheumatoid arthritis failing initial TNF inhibitor therapy: a critical review. Arthritis Res. Ther. 11(Suppl.1), S1 (2009).
6
Gomez-Reino JJ, Maneiro JR, Ruiz J et al. Comparative effectiveness of switching to alternative tumour necrosis factor (TNF) antagonists versus switching to rituximab in patients with rheumatoid arthritis who failed previous TNF antagonists: the MIRAR Study. Ann. Rheum. Dis. doi:10.1136/
www.futuremedicine.com
annrheumdis-2012-201324 (2012) (Epub ahead of print). 7
Finckh A, Ciurea A, Brulhart L et al. B cell depletion may be more effective than switching to an alternative anti-tumor necrosis factor agent in rheumatoid arthritis patients with inadequate response to anti-tumor necrosis factor agents. Arthritis Rheum. 56, 1417–1423 (2007).
8
Finckh A, Ciurea A, Brulhart L et al. Which subgroup of patients with rheumatoid arthritis benefits from switching to rituximab versus alternative anti-tumour necrosis factor (TNF) agents after previous failure of an anti-TNF agent? Ann. Rheum. Dis. 69, 387–393 (2010).
483
PRIORITY PAPER EVALUATION Finckh 9
Kekow J, Mueller-Ladner U, Schulze-Koops H. Rituximab is more effective than second anti-TNF therapy in rheumatoid arthritis patients and previous TNFa blocker failure. Biologics 6, 191–199 (2012).
10
Blom M, Kievit W, Donders AR et al. Effectiveness of a third tumor necrosis factor- a-blocking agent compared with rituximab after failure of 2 TNF-blocking agents in rheumatoid arthritis. J. Rheumatol. 38, 2355–2361 (2011).
11 Moetaza M, Hyrich K, Lunt M et al.
Rituximab or a second anti-tumor necrosis factor therapy for rheumatoid arthritis patients who have failed their first anti-tumor necrosis factor therapy? Comparative analysis from the british society for rheumatology biologics register. Arthritis Care Res. 64, 1108–1115 (2012). 12 Emery P, Gottenberg J, Sarzi-Puttini P et al.
Relative effectiveness of rituximab versus an alternative TNF inhibitor in patients with
484
rheumatoid arthritis and an inadequate response to a single previous TNF inhibitor: results from SWITCH-RA, a global, comparative-effectiveness, observational study. Arthritis Rheum 63(Suppl. 10), 126 (2011). 13 Rituximab versus anti-TNF in RA patients
who previously failed one TNF inhibitor in an observational cohort. Scand. J. Rheum. (2012) (In Press). 14
Finckh A. Comparative effectiveness of rheumatoid arthritis therapies. Curr. Rheum. Rep. 12, 348–354 (2011).
15 Gabay C, Emery P, van Vollenhoven R et al.
Tocilizumab (TCZ) monotherapy is superior to adalimumab (ADA) monotherapy in reducing disease activity in patients with rheumatoid arthritis (RA): 24-week data from the phase 4 ADACTA trial. Ann. Rheum. Dis. 71(Suppl. 3),152, Abstract LB0003 (2012). 16 Schiff M, Fleischmann R, Weinblatt M et al.
Abatacept SC versus adalimumab on
J. Compar. Effect. Res. (2012) 1(6)
background methotrexate in RA: one year results from the AMPLE study. EULAR Ann. Science Meeting. Ann. Rheum. Dis. 60, OP0022 (2012).
■■ Websites 101 Moreland LW, Genovese MC. National
Institute of Allergy and Infectious Diseases (NIAID): switching anti-TNF- a agents in RA (NCT00796705). Clinicaltrials.gov, NCT00796705 (2008). http://clinicaltrials.gov/ct2/show/NCT00796 705?term=tumour+necrosis+inadequate+resp onse&rank=5 102 Gottenberg J. Rotation or change of
biotherapy after first anti-TNF treatment failure for rheumatoid arthritis (ROC). Clinicaltrials.gov. NCT01000441 (2009). http://clinicaltrials.gov/ct2/show/NCT01000 441?term=rheumatoid+arthritis&type=Intr& cond=rheumatoid+arthritis&intr=rituximab &rank=33
future science group
