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Abstract
Objective
This study assessed the efficacy and safety of secukinumab and adalimumab in patients with active ankylosing spondylitis (AS).
Methods
A Bayesian network meta-analysis was performed with direct and indirect data collected from randomized controlled trials (RCTs) of efficacy and safety of secukinumab 75 mg, 150 mg and adalimumab 40 mg in patients with active AS.
Results
Five RCTs (1,483 patients) met the inclusion criteria. The Assessment in Spondyloarthritis International Society response criteria of ≥20% (ASAS20) response rate was significantly higher in the adalimumab 40 mg (Odds ratio [OR], 4.26; 95% credible interval [CrI], 2.09∼8.08), secukinumab 150 mg (OR, 3.35; 95% CrI, 1.73∼6.56), and 75 mg dose (OR, 2.44; 95% CrI, 1.06∼5.05) than with placebo. The ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that adalimumab 40 mg had the highest probability of being the best treatment for achieving an ASAS20 response (SUCRA=0.8753), followed by secukinumab 150 mg (SUCRA=0.7051), secukinumab 75 mg (SUCRA=0.4113), and placebo (SUCRA=0.0083). The ASAS40 response rate distribution pattern was similar to the ASAS20 response rate. However, the number of serious adverse events did not differ significantly among the treatment options.
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Figure 2.
Evidence network diagram of comparisons for network meta-analysis. The width of each edge is proportional to the number of randomized controlled trials comparing each pair of treatments, and the size of each treatment node is proportional to the number of randomized participants (sample size). (A) Placebo. (B) Secukinumab 150 mg. (C) Secukinumab 75 mg. (D) Adalimumab 40 mg.
Figure 3.
Results of the Bayesian network meta-analysis of randomized controlled studies on the relative efficacy (A: ASAS20, B: ASAS40) and safety (C) of secukinumab and adalimumab. ASAS: Assessment in Spondyloarthritis International Society, OR: odds ratio, CrI: credible interval.
Figure 4.
Inconsistency plot for the efficacy (A: ASAS20, B: ASAS40) and safety (C) of secukinumab and adalimumab. Plot of the individual data points' posterior mean deviance contributions for the consistency model (horizontal axis) and the unrelated mean effects model (vertical axis) along with the line of equality. ASAS: Assessment in Spondyloarthritis International Society.
Table 1.
Characteristics of individual studies included in the network meta-analysis
Values are presented as number. ASAS20: Assessment of Spondyloarthritis International Society 20 response criteria (improvement of ≥20% and absolute improvement of ≥1 unit [on a 10-unit scale] in at least three of the four main ASAS domains, with no worsening by ≥20% in the remaining domain) [16], NA: not available.
Table 2.
Characteristics of individual studies included in the network meta-analysis
| Study | Drugs | Age (yr) | Disease duration (yr) | Male | HLA-B27 | BASDAI |
|---|---|---|---|---|---|---|
| Kivitz, 2016 [8] | Secukinumab 150 mg | 42.1∼42.9∗ | 5.2∼6.0∗ | NA | NA | NA |
| Placebo | 42.1∼42.9∗ | 5.2∼6.0∗ | NA | NA | NA | |
| Baeten-1, 2015 [9] | Secukinumab 150 mg | 40.1±11.6 | 6.5±6.9 | 67 | 69 | 6.4±1.6 |
| Secukinumab 75 mg | 42.3±13.2 | 7.9±9.7 | 71 | 80 | 6.1±1.4 | |
| Placebo | 43.1±12.4 | 8.3±8.9 | 70 | 74 | 6.5±1.5 | |
| Baeten-2, 2015 [9] | Secukinumab 150 mg | 41.9±12.5 | 7.0±8.2 | 64 | 79 | 6.6±1.5 |
| Secukinumab 75 mg | 44.4±13.1 | 5.3±7.4 | 70 | 73 | 6.1±1.3 | |
| Placebo | 43.6±13.2 | 6.4±8.9 | 76 | 78 | 6.8±1.3 | |
| Huang, 2014 [10] | Adalimumab 40 mg | 30.1±8.7 | 3.0±3.8 | 80.8 | 95.6 | 6.0±1.4 |
| Placebo | 29.6±7.5 | 3.0±3.2 | 82.6 | 94.8 | 6.2±1.4 | |
| Lambert, 2007 [11] | Adalimumab 40 mg | 41.9±11.1 | 14.5±9.0 | 76.3 | 86.8 | 6.2±1.7 |
| Placebo | 40.0±10.9 | 12.1±8.7 | 81.8 | 81.8 | 6.5±1.6 | |
| van der Heijde, 2006 [12] | Adalimumab 40 mg | 41.7±11.9 | 11.3±9.99 | 75.5 | 78.4 | 6.3±1.7 |
| Placebo | 43.4±11.3 | 10.8±8.34 | 73.8 | 79.4 | 6.3±1.7 |
Table 3.
Characteristics of individual studies included in the network meta-analysis
| Comparison | Study | Patient |
|---|---|---|
| Placebo | 6 | 538 |
| Secukinumab 150 mg | 3 | 271 |
| Secukinumab 75 mg | 2 | 199 |
| Adalimumab 40 mg | 3 | 475 |
Table 4.
Network meta-analyses comprising the effects for all contrasts along with ORs and 95% credible intervals
Table 5.
Rank probability in terms of efficacy based on the number of patients that achieved an ASAS20 or ASAS40 response, and the safety based on the number of serious adverse events
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