POS0910 EVALUATION OF THE NONSTEROIDAL ANTI-INFLAMMATORY DRUG-SPARING EFFECT OF SECUKINUMAB IN PATIENTS WITH ANKYLOSING SPONDYLITIS: RESULTS OF THE MULTICENTER, RANDOMISED, DOUBLE-BLIND, PHASE IV ASTRUM-TRIAL
Authors: Kiltz U. , Baraliakos X. , Brandt-Juergens J. , Wagner U. , Lieb S. , Sieder C. , Mann C. , Braun J. 
Published: May 2021

Background:

Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to treat inflammatory back pain in patients (pts) with ankylosing spondylitis (AS). However, an increased risk of side effects associated with NSAIDs and their dosage has been reported1. Therefore, lower doses and a dose reduction is desirable.

Objectives:

To evaluate the short-term NSAID sparing effect of secukinumab (SEC) in AS pts with NSAID intake.

Methods:

In a prospective controlled trial, 211 adult pts with active AS (BASDAI ≥4) and an inadequate response (IR) to at least 2 NSAIDs at the highest recommended/tolerated dose and pts with an IR, or those who were naïve/intolerant to a maximum of 2 tumour necrosis factor inhibitors (TNFi) were enrolled. NSAID intake was evaluated using the ASAS-NSAID score. To be eligible, pts had to take at least 50% of the highest recommended/tolerated NSAID dose regularly. Pts were randomised (1:1:1) to receive SEC 150 mg s.c. from Week (Wk) 0 (group [gp] 1), Wk 4 (gp 2) and Wk 16 (gp 3). All groups received SEC 150 mg from Wk 16. NSAID tapering was allowed in all groups from Wk 4 onwards. The primary endpoint (PE) was an ASAS20 response of pooled gp 1 and gp 2 vs. gp 3 at Wk 12.

Results:

There were 71 pts in gp 1, 70 in gp 2 and 70 in gp 3. Baseline (BL) characteristics were comparable across groups; mean age (SD) was 45.2 (12.3) years (yrs), time since diagnosis was 7.4 (9.8) yrs, 57.8% male, 79.0% HLA-B27 positive, 48.6% pts had an elevated CRP 40.8% were current/ever smoker and 72.0% were TNFi-naïve. The ASAS-NSAID (SD) scores at BL were: gp 1 vs. gp 2 vs. gp 3: 82.9 (37.7) vs. 79.9 (45.3) vs.82.3 (39.1). BASDAI and ASDAS-CRP scores were similar between groups: 6.0 (1.4) vs. 6.2 (1.5) vs. 6.2 (1.3), and 3.4 (0.7) vs. 3.3 (0.8) vs. 3.4 (0.7), respectively. The ASAS20 response at Wk 12 of pooled gp 1 and 2 vs. gp 3 was 51.1% vs. 44.3% but PE was not met (p=0.35). A higher proportion of pts in gp 1 and 2 achieved ASAS40 and BASDAI50 and other secondary outcomes at Wk 16 (Table 1). More pts in gp 1 and 2 reduced their NSAID intake from BL through Wk 16 vs. gp 3 (Table 1 and Figure 1).

Conclusion:

In this population of pts with AS, SEC provided clinical improvements in conventional clinical outcomes and a short-term NSAID sparing effect.

References:

[1]Burmester G, et al. Ann Rheum Dis 2011;70:818-822.

Table 1.

Effect of SEC 150 mg s.c. in AS pts (Intention-to-Treat population) at Wk 16

(%), unless otherwise specifiedGroup 1 (N=71)
(SEC 150 mg from BL until Wk 20)Group 2 (N=70)
(PBO from BL until Wk 4; SEC 150 mg from Wk 4)Group 3 (N=70)
(PBO from BL until Wk 16; SEC 150 mg from Wk 16)ASAS20*56.350.041.4ASAS40*43.7§32.921.4ASAS5/6*39.4‡32.921.4ASAS-PR*8.520.0‡5.7ASAS20 TNF-IR^*60.0‡‡26.345.0 TNF-naïve^^*54.958.8‡40.0ASAS40 TNF-IR^*45.015.825.0 TNF-naïve^^*43.1‡39.2‡20.0ASDAS-CRP change (mean±SD)**-1.2±0.9§-1.0±0.9‡-0.7±0.8BASDAI change (mean±SD)***-2.3±1.9‡-2.0±2.0-1.7±2.0BASDAI50+32.428.622.9ASAS-NSAID score change (mean±SD)++-51.5±46.2‡-42.5±68.6-33.7±38.8ASAS-NSAID score decrease ≥50%*64.8‡58.642.9 <10*52.1§45.7‡28.6 =0*32.4‡38.6§17.1

AS, ankylosing spondylitis; ASAS, Assessment of SpondyloArthritis International Society; ASDAS, AS Disease Activity score; BASDAI, Bath AS Disease Activity Index; BL, baseline; CRP, C-reactive protein; IR, inadequate responder; NSAID, nonsteroidal anti-inflammatory drug; N, total number of subjects in each treatment gp; PBO, placebo; PR, partial remission; pts, patients; SEC, secukinumab; TNFi, tumour necrosis factor inhibitor; Wk, week.

†p<0.001; §p<0.01 and ‡p<0.05 vs. gp 3; ‡‡p<0.05 vs. gp 2

*p-values are from a logistic regression model with treatment, TNFi status (IR / naïve) and CRP status (>/ ≤ central lab ULN) as factors.

+p-values are from MMRM with treatment, TNFi status (IR / naïve), CRP status (>/ ≤ central lab ULN) and visit as factors, BL value as continuous covariate.

*+Missing values were imputed as non-response.

Observed data (pts) for gp 1, 2, 3, respectively:

**67, 66, 62

***67, 66, 63

++67, 67, 65

^20, 19, 20

^^51, 51, 50

Disclosure of Interests:

Uta Kiltz Speakers bureau: AbbVie, Biocad, Chugai, Eli Lilly, Grünenthal, Janssen, MSD, Novartis, Pfizer, Roche and UCB, Consultant of: AbbVie, Biocad, Chugai, Eli Lilly, Grünenthal, Janssen, MSD, Novartis, Pfizer, Roche and UCB, Grant/research support from: Abbvie, Amgen, Biogen, Fresenius, GSK, Novartis and Pfizer, Xenofon Baraliakos Consultant of: AbbVie, Biocad, Chugai, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche and UCB, Grant/research support from: AbbVie, Biocad, Chugai, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche and UCB, Jan Brandt-Juergens Speakers bureau: Abbvie, Pfizer, Roche, Sanofi-Aventis, Novartis, Lilly, MSD, UCB, BMS, Janssen, Medac, Consultant of: Abbvie, Pfizer, Roche, Sanofi-Aventis, Novartis, Lilly, MSD, UCB, BMS, Janssen, Medac, Ulf Wagner Speakers bureau: Pfizer, Novartis and Roche, Consultant of: Pfizer, Novartis and Roche, Grant/research support from: Roche, Novartis, BMS, Pfizer, Sebastian Lieb Employee of: Novartis, Christian Sieder Employee of: Novartis, Christian Mann Employee of: Novartis, Juergen Braun Speakers bureau: Abbvie, Amgen, Celltrion, Chugai, Medac, MSD, Novartis, Pfizer, Roche, and UCB, Consultant of: Abbvie, Amgen, Celltrion, Chugai, Medac, MSD, Novartis, Pfizer, Roche, and UCB, Grant/research support from: Abbvie, Amgen, Celltrion, Chugai, Medac, MSD, Novartis, Pfizer, Roche, and UCB