Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose
NNT analysis is a useful tool for putting RCT efficacy results into perspective in patient care. For clinical decision making, the NNT is a useful measure to convey statistical and clinical significance to the doctor (i.e. number of patients needed to treat to achieve 1 additional response compared to control). The most reliable data regarding how a biologic would work comes from MTX naïve RCTs as all patients are receiving active drug for the first time and selection biases may play a lesser role in determining outcomes. We performed a NNT analysis of biologics in MTX-naive pts with early RA.
Methods
PubMed was searched for randomized double-blind, MTX-controlled studies of biologics in MTX-naive pts with early RA from Jan 1990 through Dec 2013. Response rates specified by each RCT were used to assess NNT of biologic (active) versus MTX (control) where NNT=[1/(RRactive-RRcontrol)]*100. Outcomes assessed included ACR20, ACR50, and ACR70 responses as well as DAS28 remission (DAS28 <2.6).
Results
Nine published RCTs were identified.2-5Baseline age were similar across the studies (average age 50.2 yrs, range [47.2, 57.5]), but some variability in disease duration (average duration 3.3, range [0.7, 9.3]). All biologics achieved >50% response in ACR 20, although one adalimumab trial was outperformed by MTX only, leading to a negative estimated NNT. All biologics outperformed MTX only with ACR50, ACR90 and DAS28 outcomes.
Conclusion
In MTX-naïve pts with early RA, abatacept and anti-TNF agents have similar efficacy when RCT endpoints, such as ACR responses, are analyzed by NNT. Difference in efficacy appeared when more aggressive treatment goals, such as MCR and DAS28 remission, were evaluated and suggested that the likelihood of achieving these endpoints in patients was less with infliximab than other anti-TNFs or abatacept. In the absence of head-to-head clinical trial data, NNT analysis can be a useful tool for determining the relative efficacy of biologics in routine clinical practice.
|
Age |
Duration |
ACR20 |
ACR50 |
ACR70 |
DAS28 |
||||||||||
|
Paper |
Medication |
N |
(Years) |
(Years) |
N (%) |
NNT |
|
N (%) |
NNT |
|
N (%) |
NNT |
|
N (%) |
NNT |
|
OPTIMA |
MTX Only |
517 |
50.4 (13.6) |
4.5 (7.2) |
295 (57%) |
176 (34%) |
|
|
88 (17%) |
|
|
88 (17%) |
|||
|
Adalimumab 40mg+MTX |
515 |
50.7 (14.5) |
4.0 (3.6) |
361 (70%) |
8 |
|
268 (52%) |
6 |
|
180 (35%) |
6 |
|
175 (34%) |
6 |
|
|
HIT HARD |
MTX Only |
85 |
52.5 (14.3) |
1.6 (1.7) |
64 (74%) |
44 (51%) |
30 (34%) |
31 (36%) |
|||||||
|
Adalimumab 40mg+MTX |
87 |
47.2 (12.1) |
1.8 (2.1) |
57 (66%) |
-10 |
|
46 (53%) |
90 |
|
35 (40%) |
20 |
|
37 (43%) |
17 |
|
|
TEAR |
MTX Only |
255 |
48.6 (13.0) |
2.9 (5.6) |
125 (51%) |
84 (34%) |
46 (19%) |
135 (55%) |
|||||||
|
Etanercept 50mg+MTX |
244 |
50.7 (13.4) |
3.5 (6.4) |
124 (51%) |
56 |
|
93 (38%) |
19 |
|
55 (23%) |
22 |
|
138 (57%) |
28 |
|
|
IMAGE |
MTX Only |
252 |
48.1 (12.7) |
0.91 (1.1) |
161 (64%) |
106 (42%) |
63 (25%) |
33 (13%) |
|||||||
|
Rituximab 2×500 mg+MTX |
252 |
47.9 (13.4) |
0.99 (1.1) |
194 (77%) |
8 |
149 (59%) |
6 |
106 (42%) |
6 |
63 (25%) |
8 |
||||
|
Rituximab 2×1000 mg+MTX |
251 |
47.9 (13.3) |
0.92 (1.3) |
201 (80%) |
6 |
|
163 (65%) |
4 |
|
118 (47%) |
5 |
|
78 (31%) |
6 |
|
|
COMET |
MTX Only |
268 |
52.3 (0.8) |
9.3 (0.4) |
163 (59%) |
119 (43%) |
69 (25%) |
73 (27%) |
|||||||
|
Etanercept 50mg+MTX |
274 |
50.5 (0.9) |
8.8 (0.4) |
220 (80%) |
5 |
|
181 (66%) |
5 |
|
124 (45%) |
5 |
|
132 (48%) |
5 |
|
|
AGREE |
MTX Only |
253 |
49.7 (13.0) |
6.7 (7.1) |
157 (61%) |
107 (42%) |
69 (27%) |
59 (23%) |
|||||||
|
Abatacept 10mg/kg+MTX |
256 |
50.1 (12.4) |
6.2 (7.5) |
195 (76%) |
7 |
|
147 (57%) |
7 |
|
109 (43%) |
7 |
|
106 (41%) |
6 |
|
|
ASPIRE |
MTX Only |
282 |
50 (13) |
0.9 (0.7) |
151 (42%) |
91 (25%) |
60 (17%) |
42 (12%) |
|||||||
|
Infliximab 3mg/kg+MTX |
359 |
51 (12) |
0.8 (0.7) |
223 (62%) |
12 |
165 (46%) |
7 |
115 (32%) |
9 |
75 (21%) |
17 |
||||
|
Infliximab 6mg/kg+MTX |
363 |
50 (13) |
0.9 (0.8) |
240 (66%) |
8 |
|
183 (50%) |
6 |
|
135 (37%) |
6 |
|
113 (31%) |
6 |
|
|
GOBEFORE |
MTX Only |
160 |
48.6 (12.9) |
2.9 (4.8) |
79 (50%) |
47 (30%) |
25 (16%) |
18 (11%) |
|||||||
|
Golimumab 50mg+MTX |
159 |
50.9 (11.3) |
3.5 (5.7) |
98 (62%) |
8 |
64 (40%) |
9 |
38 (24%) |
12 |
40 (25%) |
7 |
||||
|
Golimumab 100mg+MTX |
159 |
50.2 (11.9) |
3.6 (6.1) |
98 (62%) |
8 |
|
58 (36%) |
14 |
|
29 (18%) |
38 |
|
31 (19%) |
12 |
|
|
PREMIER |
MTX Only |
257 |
52.0 (13.1) |
0.8 (0.9) |
144 (53%) |
111 (41%) |
72 (26%) |
64 (23%) |
|||||||
|
Adalimumab 40mg+MTX |
268 |
51.9 (14.0) |
0.7 (0.8) |
185 (69%) |
8 |
|
158 (59%) |
6 |
|
126 (47%) |
5 |
|
131 (49%) |
4 |
|
References:
- Cook RJ, Sackett DL et al. BMJ 1995;310:452–454
- OPTIMA – Kavanaugh A et al. Ann Rheum Dis 2013;72:64–71.
- HIT HARD – Detert J et al. Ann Rheum Dis 2013;72:844–850
- TEAR – Moreland LW et al. Arth Rheum 2012;64:2824-2835
- IMAGE – Tak PP et al. Ann Rheum Dis 2011;70:39–46
- COMET – Emery P et al. Lancet 2008; 372: 375–82
- AGREE – Westhovens R et al. Ann Rheum Dis 2009;68:1870–1877
- ASPIRE – St.Clair EW et al. Arth Rheum 2004;50:3432-3443
- GO BEFORE – Emery P et al. Arth Rheum 2009;60:2272-2283
- PREMIER – Breedveld FC et al. Arth Rheum 2006;54:26-37
Disclosure:
Y. Yazici,
BMS, Genentech, Celgene,
2,
Abbvie, BMS, Celgene, Genentech, Pfizer, Samumed, UCB Pharma,
5;
C. Luo,
None;
C. Swearingen,
Genentech and Biogen IDEC Inc.,
2,
Pfizer Inc,
2,
Bristol-Myers Squibb,
2.
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