Efficacy of Biologics and New Anti-Inflammatory Agents Used in the Treatment of Active Psoriatic Arthritis: Systematic Literature Review and Network Meta-Analysis of the Evidence.

Mahdi Gharaibeh¹, Yingxin Xu², Joseph Lee³, Madhura Chitnis² and David Collier⁴, ¹Amgen Inc., Thousand Oaks, CA, ²Evidera, Bethesda, MD, ³videra, Bethesda, MD, ⁴Amgen, Inc, Terni, Italy

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: ACR, meta-analysis, Outcome measures, psoriatic arthritis and tumor necrosis factor (TNF)

Session Information

Date: Monday, November 6, 2017

Title: Spondyloarthropathies and Psoriatic Arthritis – Clinical Aspects and Treatment Poster II

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose:

Psoriatic arthritis (PsA) is an inflammatory arthritis associated with psoriasis. Biologics are usually the first-line FDA-approved disease-modifying anti-rheumatic drug (DMARD) treatment; however, no published network meta-analysis (NMA) has presented efficacy results by prior biologic experience. The aim of this study is to compare the efficacy of treatments in moderate-to-severe PsA in biologic-naïve and biologic-exposed patients (pts).

Methods:

MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and conference databases for the European League Against Rheumatism, American College of Rheumatology (ACR), and British Society for Rheumatology in 2015 and 2016 were searched for randomized controlled trials published from 1/2009 to 4/2017. Treatments included were tumor necrosis factor inhibitors (TNFis; etanercept ETN, adalimumab ADA, infliximab IFX, certolizumab pegol CZP, and golimumab GOL), IL-17 inhibitors (secukinumab SEC, ixekizumab, and brodalumab BRO), phosphodiesterase 4 Inhibitor (apremilast APR) and IL-12/23 blocker (ustekinumab UST). Outcomes of interest were the proportion of pts achieving ≥20% improvement in ACR response criteria (ACR20) and proportion achieving Psoriatic Arthritis Response Criteria (PsARC) at 12 and 24 weeks; these were the most commonly used outcomes in RCTs. A Bayesian NMA estimated the comparative efficacy of these regimens via the best fitting random- or fixed-effects model.

Results:

Among 34 trials identified, 16 PsA trials for biologic-naive therapy were included, of which 5 trials also reported data for biologic-exposed pts. Pts in placebo arms received best standard of care (BSC), including non-steroidal anti-inflammatory drugs with concomitant conventional non-biologic DMARDs; BSC served as the common comparator in the NMA. Full results are shown in Table 1. For ACR20 at 12 weeks in a biologic-naïve population, the odds ratio (OR) of response for TNFis vs. BSC ranged from 3.36 for CZP to 19.49 for ETN and from 2.33 for BRO280 to 2.54 for APR in other biologics. At 24 weeks, the OR of response for TNFis vs. BSC ranged from 4.28 for CZP to 11.26 for GOL and from 2.64 for UST45 to 6.77 for SEC150 in other biologics. For ACR20 at 24 weeks in a biologic-exposed population, the OR of response for the TNFi CZP was 12.38 and ranged from 2.97 for SEC150 to 5.65 for SEC300 in other biologics. For PsARC at 12 weeks in a biologic-naïve population, the OR of response for TNFis ranged from 4.22 for ADA to 24.75 for ETN while it ranged from 5.02 for IFX to 13.8 for GOL100 at 24 weeks in other biologics.

Conclusion:

Response rates vary greatly with DMARD treatment. There was a trend for higher odds of response with TNFis vs. other treatments in biologic-naïve PsA pts. There were too few biologic-exposed outcomes to draw any conclusions. The results of this NMA suggest that TNFis show improved response for joint outcomes in PsA pts.

Biologics vs. BSC* OR [95% credible interval]	Biologic Naïve PsA				Biologic Exposed PsA
Biologics vs. BSC* OR [95% credible interval]	ACR 20 @12wks	ACR 20 @24wks	PsARC @12wks	PsARC @24wks	ACR20 @24wks
Adalimumab	6.53 [2.84, 13.12]	7.78 [3.16, 19.43]	4.22 [1.82, 9.26]	5.2 [1.38, 20.05]	—
Etanercept	19.49 [4.47, 98.69]	4.93 [1.92, 12.9]	24.75 [4.89, 144.17]	8 [2.07, 31.85]	—
Golimumab 50mg	11.03 [3.91, 33.38]	7.85 [3.03, 20.99]	10.4 [3.43, 32.04]	5.67 [1.47, 21.85]	—
Golimumab 100mg	8.81 [3.13, 26.68]	11.26 [4.34, 30.33]	9.73 [3.22, 29.84]	13.8 [3.54, 54.71]	—
Infliximab	13.45 [6.27, 32.46]	6.28 [2.42, 16.91]	10.22 [4.39, 24.22]	5.02 [1.26, 19.11]	—
Certolizumab (Pooled)	3.36 [1.3, 8.7]	2.64 [1.36, 5.28]	—	—	12.38 [3.65, 60.28]
Apremilast 30mg	2.54 [1.4, 4.59]	—	—	—	—
Brodalumab 140mg	2.37 [0.6, 10.61]	—	—	—	—
Brodalumab 280mg	2.33 [0.54, 10.8]	—	—	—	—
Ustekinumab 45mg	—	3.32 [1.68, 6.47]	—	—	3.51 [1.49, 9.08]
Ustekinumab 90mg	—	4.28 [1.78, 10.57]	—	—	3.19 [1.33, 8.26]
Secukinumab 150mg	—	6.77 [3.54, 14.28]	—	—	2.97 [1.49, 6.12]
Secukinumab 300mg	—	6.27 [2.41, 16.76]	—	—	5.65 [2.08, 16.14]

*BSC: NSAIDs (51 to 86%), MTX (36 to 71%), other cDMARDs (2 to 7%).

Disclosure: M. Gharaibeh, Amgen, 1,Amgen, 3; Y. Xu, Amgen, 5; J. Lee, Amgen, 5; M. Chitnis, Amgen, 5; D. Collier, Amgen, 1,Amgen, 3.

To cite this abstract in AMA style:

Gharaibeh M, Xu Y, Lee J, Chitnis M, Collier D. Efficacy of Biologics and New Anti-Inflammatory Agents Used in the Treatment of Active Psoriatic Arthritis: Systematic Literature Review and Network Meta-Analysis of the Evidence. [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/efficacy-of-biologics-and-new-anti-inflammatory-agents-used-in-the-treatment-of-active-psoriatic-arthritis-systematic-literature-review-and-network-meta-analysis-of-the-evidence/. Accessed .

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