Summary of findings for the main comparison. Abatacept (2 and 10mg/kg) + DMARDs/biologic versus placebo + DMARDs/biologic for rheumatoid arthritis.
| Abatacept (2 and 10mg/kg) + DMARDs/biologic versus placebo + DMARDs/biologic for rheumatoid arthritis | ||||||
| Patient or population: patients with rheumatoid arthritis Settings: Intervention: Abatacept (2 and 10mg/kg) + DMARDs/biologic Comparison: Placebo + DMARDs/biologic | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect (95% CI) | No of Participants (studies) | Quality of the evidence (GRADE) | Comments | |
| Assumed risk | Corresponding risk | |||||
| Placebo + DMARDs/biologic | Abatacept (2 and 10mg/kg) + DMARDs/biologic | |||||
| ACR 50% improvement Follow‐up: 12 months | RR 2.21 (1.73 to 2.82) | 993 (3 studies) | ⊕⊕⊕⊝ moderate1,2,3 | Absolute risk difference= 21% (16% to 27%). Relative percent change=121% (73% to 182%). NNT=5 (4 to 7)4 | ||
| 168 per 1000 | 371 per 1000 (291 to 474) | |||||
| Pain measured at end of study on a 100 mm visual analog scale. Scale from: 0 (better) to 100 (worse). Follow‐up: 12 months | The mean pain in the control groups was 49.24 mm | The mean pain in the intervention groups was 10.71 lower (12.97 to 8.45 lower) | 1425 (1 study5) | ⊕⊕⊕⊝ moderate2 | Absolute risk difference=‐11% (‐13% to ‐8.5%). Relative percent change=‐18% (‐22% to ‐14%). NNT=5 (4 to 6)4 | |
| Improvement in physical function (HAQ: greater than 0.3 increase from baseline, 0‐3 scale) Follow‐up: 12 months | RR 1.62 (1.35 to 1.95) | 638 (1 study6) | ⊕⊕⊕⊝ moderate1 | Absolute risk difference= 24% (16% to 32%). Relative percent change= 62% (35% to 95%). NNT=5 (4 to 7)4 | ||
| 393 per 1000 | 637 per 1000 (531 to 766) | |||||
| Achievement of low disease activity state (DAS 28 less than 3.2, scale 0‐10) Follow‐up: 12 months | RR 4.33 (2.84 to 6.59) | 638 (1 study6) | ⊕⊕⊕⊝ moderate1 | Absolute risk difference=33% (26% to 39%). Relative percent change=333% (184% to 559%). NNT=4 (3 to 5)4 | ||
| 98 per 1000 | 424 per 1000 (278 to 646) | |||||
| Total serious adverse events Follow‐up: 6 to 12 months | RR 1.05 (0.87 to 1.28) | 3151 (6 studies) | ⊕⊕⊕⊝ moderate1,2,3,7 | Absolute risk difference=1% (‐2% to 3%). Relative percent change=5% (‐14% to 29%). NNT=n/a4 | ||
| 121 per 1000 | 127 per 1000 (105 to 155) | |||||
| Change in radiographic progression measured by Genant‐modifed Sharp erosion score (increase in score means more joint damage). Scale from: 0 to 145. Follow‐up: 12 months | The median change in radiographic progression in the control group was 0.27 units | The median change in radiographic progression in the intervention group was 0 units | 586 (1 study6) | ⊕⊕⊕⊝ moderate1,8 | Note there was no change in the abatacept group. MD ‐0.27 (‐0.42, ‐0.12). Absolute RD=‐0.2% (‐0.3% to ‐0.08%). Relative percent change=‐1.2% (‐1.9% to ‐0.6%). 9 | |
| Long‐term serious adverse events Follow‐up: 2 years | See comment | See comment | Not estimable | 950 (2 studies11) | ⊕⊕⊝⊝ low10 | Number of patients with SAE: Genovese 2005: 103/357; 23.4 SAE/100 patient‐years; 70% completed the LTE. Kremer 2006: 149/593; 16.3 SAE/100 patient‐years; 90.5% completed the LTE. |
| *The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio; | ||||||
| GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate. | ||||||
1 Kremer 2006: Intention to treat analysis not performed. 9 patients in abatacept group and 5 in placebo group excluded from analysis. 2 Weinblatt 2006: 15 people randomized were not treated and not included in analysis 3 Kremer 2003: Risk of attrition bias ‐ less than 80% completion rate in treatment group at 12 months 4 NOTE: Number needed to treat (NNT)=n/a when result is not statistically significant. NNT for dichotomous outcomes calculated using Cates NNT calculator (http://www.nntonline.net/visualrx/). NNT for continuous outcomes calculated using Wells Calculator (CMSG editorial office). 5 Outcome based on Weinblatt 2006 6 Outcome based on Kremer 2006 7 Weinblatt 2007: Risk of attrition bias ‐ less than 80% completion rate in the treatment group at 12 months 8 Radiographic data obtained for 90% of study participants 9 RD=risk difference 10 Long‐term serious adverse events based on observational data. Two RCTs had a long‐term extension (LTE) phase in which people in the placebo group during the RCT switched to abatacept for the LTE. 11 Based on 2 long‐term extension studies (LTE) of RCTs. Participants on placebo in the RCT switched to abatacept treatment.