Review ArticleReview

Abatacept for Rheumatoid Arthritis: A Cochrane Systematic Review

LARA J. MAXWELL and JASVINDER A. SINGH
The Journal of Rheumatology February 2010, 37 (2) 234-245; DOI: https://doi.org/10.3899/jrheum.091066

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Abstract

Objective. To perform a systematic review of efficacy and safety of abatacept in patients with rheumatoid arthritis (RA).

Methods. We searched the Cochrane Library, MEDLINE, EMBASE, ACP Journal Club, and Biosis Previews for randomized controlled trials (RCT) comparing abatacept alone or in combination with disease modifying antirheumatic drugs (DMARD)/biologics to placebo or other DMARD/biologics in patients with RA. Two reviewers independently assessed search results, risk of bias, and extracted data.

Results. Seven trials with 2908 patients were included. Compared with placebo, patients with RA treated with abatacept were 2.2 times more likely to achieve an American College of Rheumatology 50% response (ACR50) at one year (relative risk 2.21, 95% CI 1.73, 2.82) with a 21% (95% CI 16%, 27%) absolute risk difference between groups. The number needed to treat to achieve an ACR50 response was 5 (95% CI 4, 7). Significantly greater improvements in physical function, disease activity, pain, and radiographic progression were noted in abatacept-treated patients compared to placebo. Total adverse events (AE) were greater in the abatacept group (RR 1.05, 95% CI 1.01, 1.08). Other harm outcomes were not significant, with the exception of serious infections at 12 months, which were more common in the abatacept group versus control group (Peto odds ratio 1.91, 95% CI 1.07, 3.42). Serious AE were more numerous in the abatacept + etanercept group versus the placebo + etanercept group (RR 2.30, 95% CI 1.15, 4.62).

Conclusion. Abatacept seems to be efficacious and safe in the treatment of RA. Abatacept should not be used in combination with other biologics to treat RA. Further longterm studies and postmarketing surveillance are required to assess for longer-term harms and sustained efficacy.

Key Indexing Terms:

Abatacept was approved by the US Food and Drug Administration (FDA) in December 2005 for treatment of moderate to severe rheumatoid arthritis (RA) in adult patients who have not responded adequately either to oral disease-modifying antirheumatic drugs (DMARD; such as methotrexate) or to the tumor-necrosis factor-α (TNF-α) antagonists1. It is the first biologic therapy to selectively modulate costimulation, inhibiting T cell (T lymphocyte) activation by binding to CD80 and CD86 (the costimulatory antigens), thereby blocking interaction with CD28 (the costimulatory receptor)2. Use of abatacept is associated with reduction in joint inflammation, pain, and joint damage in patients with active RA.

The use of biologics is limited by their high costs and uncertainty about the adverse events. The cost for one year of abatacept treatment is roughly US $22,0003 and Canadian $18,4804. The aim of this systematic review was to examine the data from randomized controlled trials (RCT) of abatacept to quantify its benefits and potential harms.

MATERIALS AND METHODS

Types of studies, participants, and interventions

We included RCT of 3 months or longer duration comparing abatacept alone or in combination with DMARD or biologics to placebo or other DMARD or biologics in adults meeting the American College of Rheumatology (ACR) 1987 revised criteria for RA5. Data from published and unpublished RCT were considered for inclusion with no restrictions by duration of intervention or the dose used.

Outcome measures

The co-primary outcomes were efficacy as assessed by 50% improvement in American College of Rheumatology criteria (ACR50)6 and safety. An ACR20/50/70 response is defined as a 20%/50%/70% improvement in tender and swollen joint counts and the same level of improvement in 3 of the 5 following variables: patient and physician global assessments, pain, patient assessment of functional ability [using the Stanford Health Assessment Questionnaire (HAQ) or other measures], and acute-phase reactants [erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP)]6. We assessed safety by comparing the number of total and serious adverse events; specific adverse events, including allergic reactions, infections, serious infections, lymphoma; and withdrawals due to adverse events and all withdrawals. Regulatory agency websites were also reviewed for potential longer-term adverse events.

Secondary outcome measures included the following: (1) ACR20 and ACR70 response criteria and individual ACR criteria (as outlined above)6; (2) radiographic progression (measured by the Sharp, modified Sharp, or Larsen scores)7,8; (3) Disease Activity Score (DAS; scale 0–10)9, a composite index including tender and swollen joint counts, patient’s global assessment of disease activity, and ESR, or DAS28; (4) European League Against Rheumatism (EULAR) response criteria10,11; (5) physical function as measured by changes in HAQ or modified HAQ12,13 scores, proportion achieving “minimal clinical important change” (MCID), defined as ≥ 0.2214 or ≤ 0.306; (6) health-related quality of life (HRQOL) measured by Medical Outcomes Study Short-Form 36 (SF-36) physical and mental HRQOL15,16.

Search methods for identification of studies and additional data

A trained Cochrane librarian searched the following electronic databases up to March 2007 and updated the search December 31, 2008: MEDLINE, EMBASE, ACP Journal Club, ISI Web of Science (Biosis Previews for ACR and EULAR abstracts) and The Cochrane Library, Issue 1 [including the Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Systematic Reviews (CDSR), Database of Abstracts of Reviews of Effects (DARE), and Health Technology Assessments (HTA)]. The reference lists of identified clinical trials and reviews were also searched. For missing information, clarifications, and additional unpublished data, we contacted the authors of included studies and the manufacturer of abatacept. The original search strategy was not limited by language, year of publication, or type of publication.

For safety assessment, we searched the websites of the regulatory agencies (US Food and Drug Administration, European Medicines Evaluation Agency, Australian Adverse Drug Reactions Bulletin, and UK pharmacovigilance and drug safety updates) using the terms “rheumatoid arthritis,” “abatacept,” and “orencia” on April 1, 2009.

Data collection and analysis

Analyses were determined a priori and published as a Cochrane Library protocol16a. Two reviewers independently assessed search results (LM, JS) and disagreement was resolved by consensus. Data from the included trials was independently extracted by 2 reviewers (LM, JS) and entered into Review Manager 5.0 (RevMan 5.0)17. For missing variance measures for continuous outcomes, we obtained additional data from the authors and Bristol-Myers Squibb.

Using a structured data extraction form, we obtained study characteristics, study population characteristics, intervention characteristics, outcome measures, and results for the intention-to-treat (ITT) population (if reported).

Assessment of methodological quality

The risk of bias of the included studies was assessed by 2 independent reviewers (LM, JS), as recommended by the Cochrane Handbook18, examining the domains of randomization sequence generation, allocation sequence concealment, blinding of participants, personnel and outcome assessors, incomplete outcome data (primary outcome data reporting, dropout rates and reasons for withdrawal, appropriate imputation of missing data, an overall completion rate ≥ 80%), and selective outcome reporting and other potential threats to validity (considering external validity, e.g., relevant use of cointerventions, bias due to funding source). Each criterion was explicitly judged as follows: Yes = low risk of bias; No = high risk of bias; Unclear = either lack of information or uncertainty about potential for bias.

Statistical analysis

For the main analyses, we compared abatacept (10 mg/kg and 2 mg/kg combined) + DMARD or biologics versus placebo + DMARD or biologics.

When data were sufficiently homogeneous, both clinically and statistically, we performed a metaanalysis. We calculated the mean difference (MD) or standardized mean difference (SMD) for the continuous outcomes, depending on similarity of scales measuring an outcome. For the dichotomous data, we calculated the relative risk (RR), or in the case of rare events (< 10%; i.e., death), Peto odds ratio (Peto OR) was used.

Heterogeneity of data was assessed by 3 methods: (1) visually by examining the forest plots; and formally tested using (2) the chi-square, with a p value < 0.10 indicating significant heterogeneity, and (3) the I2 statistic19, with values > 50% indicating substantial heterogeneity. When substantial heterogeneity was detected, we explored the data further by performing subgroup analyses, in an attempt to explain the heterogeneity.

We used a fixed-effects model (specified a priori), since abatacept is a new biologic and we expected that RCT would have been performed in similar populations with little “between-study” variation. In cases where significant heterogeneity was found and could not be explained, a random-effects model was used. We assessed the possibility of publication bias using a funnel plot.

We assessed results separately by dose, disease duration, and prior DMARD failure planned a priori. In response to concerns found in an RCT of abatacept in combination with etanercept20, we undertook a post-hoc analysis to assess the effect of harms in patients on a background therapy of biologic treatment.

We performed the following sensitivity analyses (specified a priori) in order to explore effect size differences and the robustness of conclusions: (1) effect of study quality, defined as adequate allocation concealment and outcome assessor blinding; and (2) effect of imputation of missing data or statistical transformations. We calculated the number needed to treat (NNT) from the control group event rate, and the relative risk was calculated using the Visual Rx NNT calculator21. For continuous outcomes, the NNT was calculated using the Wells calculator software available at the Cochrane Musculoskeletal Group editorial office.

RESULTS

Figure 1 shows a diagram of the search results. Twelve articles corresponding to the following 7 clinical trials met the inclusion criteria: Genovese 200522; Kremer 200323; Kremer 200624; Moreland 200225; Weinblatt 200626; Weinblatt 200720; and Schiff 200827. The remaining 5 publications reported additional outcomes from the main trials: Kremer 200527a, Emery 200628, Russell 200729, Westhovens 200630, and Cole 200831. All trials except Moreland 200225 and Schiff 200827 reported a randomization ratio of 2:1 for treatment to control. Moreland 200225 had 6 treatment arms and one placebo. Schiff 200827 had 2 treatment arms (abatacept or infliximab) and one placebo (randomized 3:3:2 to abatacept, infliximab, and placebo).

Figure 1
Figure 1

Selection of studies for this systematic review.

The study characteristics are presented in Table 1. A summary of findings (Table 2) shows key outcomes. The results of the search of pharmacovigilance websites is summarized in Table 3.

View this table:
Table 1

Details of studies.

View this table:
Table 2

Summary of findings: comparison of abatacept (2 and 10 mg/kg) + DMARD/biologic versus placebo + DMARD/biologic for RA.

View this table:
Table 3

Safety warnings from regulatory agencies in a Web search up to April 1, 2009.

Seven trials with 2908 patients were included in this analysis. Most were multicenter, international RCT. Altogether 1863 patients were randomized to abatacept and 1045 to placebo. The majority of patients were White women with mean age in mid-50s (range 48.3–55.8 yrs in the control group) with active RA despite treatment with DMARD23,24,27, anti-TNF therapy20,22, or DMARD or biologics25,26. The average RA disease duration was between 8 and 13 years, except in one study where it was only 3.4 years25.

Abatacept was administered intravenously in all trials. Most trials used a dosage of abatacept of 10 mg/kg + DMARD with 3 exceptions: in Moreland 200225, 2 mg/kg dose was also used and no concurrent DMARD use was allowed; in Weinblatt 200720, only 2 mg/kg dose was used and patients also received etanercept; and in Kremer 200323, 2 doses were used (2 and 10 mg/kg). Schiff 200827 had 2 treatment arms (abatacept or infliximab) and one placebo arm. Trial duration ranged from 85 days to 12 months. All trials were sponsored by Bristol-Myers Squibb, the manufacturer of abatacept.

The risk of bias for each included study is summarized in Figure 2 (additional details available from the author upon request). For the primary outcome ACR50 response, the studies included in the metaanalysis rate well in terms of adequate allocation concealment, blinding, and reporting of appropriate outcomes. However, there is a concern of bias in terms of incomplete outcome data given the high dropout rate in 2 studies20,23, and that 2 studies excluded participants from efficacy analyses, but included them in safety analyses24,26. All studies were sponsored by the manufacturer of abatacept and it is known that industry-sponsored trials may overestimate the treatment effect32.

Figure 2
Figure 2

A summary of methodological quality for each study across 6 domains. “+”: criteria were met; “–”criteria were not met; “?”: unclear if criteria were met.

Primary outcomes

Abatacept was associated with significantly higher likelihood of achieving ACR50 compared to placebo at 6 and 12 months, but not at 3 months (only one study) with RR of 2.47 (95% CI 2.00, 3.07), 2.21 (95% CI 1.73, 2.82), and 2.50 (95% CI 0.52, 11.96), respectively (Figure 3). The moderate heterogeneity for 6-month results (I2 = 44%, p = 0.13) decreased when analyses were performed by excluding the Weinblatt 2007 trial20, which was the only trial to use abatacept 2 mg/kg in combination with etanercept and not statistically significant; however, the pooled RR changed minimally, to 2.59 (95% CI 2.07, 3.25). For the ACR50 response, there was an absolute difference of 21% (95% CI 16%, 27%; Table 2). The NNT to achieve an ACR50 response at 1 year was 5 (95% CI 4 to 7).

Figure 3
Figure 3

Metaanalysis of the risk of achieving an ACR50 response at 3, 6, and 12 months. There is low heterogeneity when the results from different studies are pooled. Abatacept has a statistically significantly better risk of achieving an ACR50 response than placebo (results favor abatacept).

We found that the total number of adverse events was significantly greater in the abatacept group compared to placebo but the relative risk was low (RR 1.05,95% CI 1.01,

1.08; Figure 4A). We noted a greater number of serious infections at 12 months in the abatacept-treated group (Peto OR 1.91, 95% CI 1.07, 3.42; Figure 4B). This analysis included the Weinblatt 2007 trial20 in which abatacept was given in combination with etanercept. Removing this study resulted in a lower OR, which was just statistically significant (Peto OR 1.82, 95% CI 1.00, 3.32). Total withdrawals favored the abatacept-treated group (RR 0.60, 95% CI 0.52, 0.70). Numbers of total serious adverse events, withdrawals due to adverse events, serious infections, upper respiratory infections, cough, nausea, malignancies, and mortality were not statistically significantly different between the treatment and control groups, based on pooled results at 6 and 12 months. There was a higher number of headaches and infusion reactions reported in the abatacept group (details available from the author upon request). We undertook a post hoc analysis to assess the effect of harms in patients on a background therapy of biologic treatment (for both 2 mg and 10 mg/kg doses) compared to placebo. The RR of total serious adverse events in the abatacept group was statistically significantly greater than that in the placebo group, 2.30 (95% CI 1.15, 4.62), as well as withdrawals due to adverse events (Peto OR 2.68, 95% CI 1.07, 6.72).

Figure 4
Figure 4

A. Metaanalysis of the risk of adverse events at 3 and 6 months and pooled for the 2 timepoints. There is low heterogeneity when the results from different studies are pooled. Abatacept has a statistically significantly higher risk of an adverse event than placebo (results favor placebo). B. Metaanalysis of the risk of serious infection at 3 and 6 months and pooled for the 2 timepoints. There is low heterogeneity when the results from different studies are pooled. Abatacept has a statistically significantly higher risk of serious infection than placebo (results favor placebo) at 12 months, but the pooled result is not significant.

Table 3 summarizes the safety warnings from regulatory agencies.

Secondary outcomes

Significantly more abatacept-treated patients compared to control group achieved an ACR20 response at 6 and 12 months, but not at 3 months (1 study) with RR of 1.79 (95% CI 1.59, 2.02), 1.79 (95% CI 1.55, 2.07), and 1.70 (95% CI 0.93, 3.12), respectively. A significantly greater proportion achieved an ACR70 response compared to placebo at 6 and 12 months, but not at 3 months, with RR 3.53 (95% CI 2.41, 5.16), 4.02 (95% CI 2.62, 6.18), and 5.00 (95% CI 0.25, 100.2), respectively.

Only one RCT reported radiographic results using the Genant-modified Sharp score24 and it found that compared to placebo, abatacept statistically significantly reduced the progression of joint damage after 12 months, although the progression was minimal in both groups. It reported a 50% reduction in change from baseline values in the abatacept group compared to placebo at 12 months. With respect to median change from baseline, there was no change in the abatacept group and a 0.27 change in the placebo group for the erosion score. Due to missing variance, using an approximation, there was a statistically significant mean difference in favor of abatacept (mean difference –0.27, 95% CI –0.42, –0.12).

The ACR core components — patient global assessment, physician global assessment, physical function, tender joint count, and swollen joint count — were all statistically significant in favor of abatacept. Patient-reported pain was significantly reduced in the abatacept group compared to placebo22–26 (Table 2).

The abatacept group was significantly more likely to reach a low disease activity state (DAS28 < 3.2, scale 0–10) at 6 and 12 months, with RR of 3.36 (95% CI 2.28, 4.96) and 4.33 (95% CI 2.84, 6.59), respectively (Table 2). At 12 months, there was an absolute difference of 33% (95% CI 26%, 39%) in achievement of a low disease activity state (DAS28 < 3.2) between abatacept and placebo; the corresponding NNT was 4 (95% CI 3 to 5). Those in the abatacept group were significantly more likely to achieve disease remission (defined as DAS28 < 2.6) at 12 months, with RR 12.74 (95% CI 4.76, 34.15).

Clinically meaningful improvement in physical function on the HAQ (> 0.22 or > 0.3 increase from baseline; results similar regardless of the definition used) was noted in significantly more abatacept-treated than placebo patients at 6 and 12 months, with RR of 1.73 (95% CI 1.41, 2.13) and 1.62 (95% CI 1.35, 1.95), respectively (Table 2). The absolute risk difference of clinically meaningful improvement in HAQ (> 0.3) was 24% (95% CI 16%, 32%) at 12 months in favor of abatacept. The NNT to achieve a HAQ > 0.3 response at 1 year was 5 (95% CI 4 to 7).

A significantly greater proportion of patients in the abatacept group than in the placebo group reported “better” scores on the physical (PCS) and mental component summary (MCS) scores, with pooled RR of 1.90 (95% CI 1.52, 2.39) and 1.42 (95% CI 1.15, 1.76), respectively. In the only study reporting this outcome, a significantly greater proportion of the abatacept-treated group compared to placebo achieved the SF-36 PCS population norms at 6 months, with RR 2.36 (95% CI 1.34, 4.14)22. On the continuous scale, the pooled mean difference in PCS and MCS scores was statistically significant in favor of abatacept at 4.29 (95% CI 3.22, 5.35) and 2.72 (95% CI 1.57, 3.87). [Other outcomes are available from the author upon request.]

Subgroup analyses

Eligibility criteria: Trials were grouped according to whether eligibility criteria for the trial required patients to be inadequate responders to methotrexate/DMARD23,24,27, inadequate responders to anti-TNF-α drugs20,22, or both25,26. An ACR20/50/70 response was significant in the abatacept group compared to placebo in both inadequate responders to methotrexate and inadequate responders to biologic therapy. However, the pooled analysis of the ACR50 response in the biologic failure group had high heterogeneity, most likely due to the pooling of trials using different interventions (abatacept + DMARD22 compared to abatacept + etanercept20).

Dose: There were no major changes to the relative risks once the 2 mg/kg dose was removed from the analysis of the combined dose. The 2 mg/kg dose was given in combination with etanercept and it was not statistically significant at any timepoint.

Disease duration: All studies except Moreland 200225 enrolled patients with a disease duration greater than 8 years. As Moreland 200225 was a pilot study that provided only 3-month data, this subgroup analysis was not undertaken.

Effect of study quality: All studies except Schiff 2008 (unclear allocation concealment)27 reported adequate allocation concealment and blinding. Excluding Schiff 200827 from the ACR50 response at 6 months did not change the result significantly: with Schiff 2008, ACR50 RR 2.47 (95% CI 2.00, 3.07) and excluding Schiff 2008 ACR50, RR 2.62 (95% CI 2.05, 3.37).

Publication bias

Publication bias was assessed using a funnel plot of the ACR50 response at 6 months (details available from the author upon request). With inclusion of only 5 trials, there does not appear to be evidence of publication bias in this review (Moreland 2002 did not provide 6-month data25 and Weinblatt 200626 did not measure ACR50).

DISCUSSION

In this Cochrane systematic review of 7 RCT of abatacept including 2908 patients with RA (1863 treated with abatacept; 1045 treated with placebo), we examined the efficacy and short-term safety of abatacept alone or in combination with DMARD/biologics compared to placebo alone or in combination with DMARD/biologics. Abatacept was 1.7 to 4 times more efficacious than placebo in achieving an ACR20, ACR50, and ACR70 response at 12 months. In terms of the absolute risk difference between treated and control groups, the ACR50 at 12 months had a 21% absolute difference (95% CI 16% to 27%). The number needed to treat (NNT) in order to achieve an ACR50 response at one year was 5 (95% CI 4 to 7). This NNT is similar to NNT of 3.0 (95% CI 2.0 to 6.0) found in a systematic review of another biologic agent, adalimumab, an anti-TNF-α inhibitor, in patients with moderate to severe disease and failure to previous DMARD33. Abatacept-treated patients were 3.4 to 4.3 times more likely to achieve a low disease activity state. One RCT24 demonstrated that at 12 months abatacept statistically significantly slowed the progression of structural joint damage compared with placebo, although the clinical significance of this result is not known. The ACR20, ACR50, and ACR70 responses in the original abatacept group at one year were similar to those at 2 years: 81.9% and 80.3%; 54.0% and 55.6%; 32.4% and 34.3%, respectively34. Radiographic progression, disease activity (measured by DAS28), physical function (measured by HAQ-Damage Index), and HRQOL (measured by SF-36) outcome responses were also maintained at 2 years35. Thus, it appears that response to abatacept therapy is well maintained.

The efficacy must be balanced by assessment of safety. Numbers of adverse events and serious infections were significantly greater in the abatacept group compared to placebo group but the totals of serious adverse events, withdrawals due to adverse events, upper respiratory infections, malignancies, and mortality were not statistically significantly different. This may be due to small sample size36,37 and short followup duration. The FDA website highlighted the increase in serious infections, lymphoma, and lung cancer in patients taking abatacept compared to placebo38, similar to the European Public Assessment Report’s Scientific Discussion document on abatacept describing possible increased risk for infection and autoimmune disorders39. The FDA label included a warning against using abatacept concurrently with anti-TNF therapy and the European Medicines Agency suggested that risk of malignancies needs further investigation (Table 3).

With the current evidence of its superiority to placebo, head-to-head comparator trials of abatacept with other DMARD/biologics, such as TNF inhibitors and others, may help us better understand its role in RA treatment40. This information will also assist patients and physicians in making more informed choices.

Two recent reviews of abatacept described the outcomes from Phase II and III trials, but did not perform metaanalyses41,42. In a recent metaanalysis of RCT to investigate the risk of serious infections in use of rituximab, anakinra, and abatacept for RA, Salliot, et al reported no significant increase in risk of serious infection with the use of abatacept in 5 trials with a pooled Mantel-Haenszel OR of 1.35 (95% CI 0.78 to 2.32)43. Similarly, we found no significant increase in serious infections with Peto OR of 1.56 (95% CI 0.93 to 2.61), when 6 and 12-month results were pooled. However, the pooled 12-month results of 3 trials did show statistically significantly higher odds of serious infections in the abatacept versus placebo-treated patients (Peto OR 1.91, 95% CI 1.07 to 3.42).

A subgroup analysis based on eligibility criteria of an inadequate response to DMARD therapy versus an inadequate response to anti-TNF therapy found that in both groups abatacept produced a statistically significant ACR50 response compared to placebo at 6 months. The group with an inadequate response to anti-TNF therapy had a slightly higher relative risk for an ACR50 response at 6 months than those with an inadequate response to DMARD therapy, but the difference between the 2 groups was not significant. Therefore, based on placebo-controlled trials of up to one year duration, it appears that abatacept is efficacious in improving signs and symptoms of patients with active, moderate to severe RA who have failed either DMARD or anti-TNF therapy.

Study strengths

For this review a systematic literature search was performed; 2 reviewers reviewed abstracts independently, extracted data independently, and resolved disagreements with consensus. We obtained additional information from the authors and Bristol-Myers Squibb, and specified analyses a priori in a published protocol16a.

Study limitations

We were limited in our ability to perform metaanalysis due to lack of reporting of variance measures, to assess risk of bias due to missing details, and to uniformly analyze adverse events due to use of different systems (MedDRA version 7 versus version 8 versus a specified list) — all limitations of the included studies. Due to lack of RCT of abatacept in patients with early RA, its efficacy in early RA is unknown. Pooling the trials with 2 mg/kg and 10 mg/kg dosages of abatacept, which was done to increase the sample size, may have led to slight underestimation of adverse events than if we had included only data for the 10 mg/kg dosage. At best, RCT provide estimates of short-term safety; long-duration observational and postmarketing surveillance studies are needed for the assessment of intermediate to longterm safety to detect uncommon, rare adverse events. Methodological quality was good in general, with a few exceptions: < 80% completion rates in the treatment group in 2 studies20,23, and only 3 out of 7 trials reported a proper intention-to-treat analysis.

We conclude that there is “moderate” level evidence for short-term efficacy of abatacept compared to placebo in improving disease activity and state, physical function, and HRQOL. Abatacept appears safe for short-term use. There is no efficacy benefit of combining abatacept with an anti-TNF biologic, which leads to higher risks. Further trials/studies are needed to determine its longterm safety profile and to assess whether the level of efficacy found in the RCT included in our review is sustained over time.

Footnotes

  • The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the Cochrane Collaboration. None of the authors has any financial interest, direct or indirect (dual commitment), that might affect, or be perceived to affect, the conduct or reporting of the work submitted herewith.

  • This report is based on a Cochrane review published in The Cochrane Library 2009, Issue 4 (see www.thecochranelibrary.com for information). Cochrane reviews are regularly updated as new evidence emerges and in response to feedback, and The Cochrane Library should be consulted for the most recent version of the review.

  • Supported by NIH CTSA Award 1 KL2 RR024151-01 (Mayo Clinic Center for Clinical and Translational Research).

    • Accepted for publication September 25, 2009.

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