Impact of baseline C-reactive protein levels on the response to secukinumab in ankylosing spondylitis: 3-year pooled data from two phase III studies

Abstract

Objective: To evaluate the magnitude of response to secukinumab treatment over 3 years in patients with ankylosing spondylitis (AS) grouped by baseline C-reactive protein (CRP) levels in a pooled study of two pivotal phase III studies: MEASURE 1 (NCT01358175) and MEASURE 2 (NCT01649375).

Methods: This post hoc analysis pooled data from all patients with available baseline CRP in the two studies who received subcutaneous secukinumab 150 mg (approved dose; N=197) or placebo (N=195). Assessed efficacy endpoints included Assessments of SpondyloArthritis international Society (ASAS)20/40, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), BASDAI50, AS Disease Activity Score inactive disease and ASAS partial remission among patients grouped by baseline CRP based on central laboratory cut-off <5 mg/L (normal) or ≥5 mg/L (elevated) and a cut-off <10 mg/L or ≥10 mg/L.

Results: At baseline, 36.5% (143/392) patients had normal and 63.5% (249/392) had elevated CRP. At week 16, ASAS20/40 response rates were higher for secukinumab versus placebo in normal (56.9%/34.7% vs 28.2%/7.0%; p<0.01/p<0.001) and in elevated (63.2%/42.4% vs 29.0%/15.3%; both p<0.0001) CRP groups. Improvement was reported for all outcomes (p<0.05) in both groups, except for ASAS partial remission in the normal CRP group, where a numerical difference 12.5% vs 2.8%, p=0.07) was observed. Similar trends of improvement were observed in the <10 and ≥10 mg/L groups across all efficacy outcomes at week 16. Treatment responses to secukinumab in all CRP groups further improved over 156 weeks.

Conclusion: Secukinumab 150 mg demonstrated rapid and sustained efficacy in patients with AS irrespective of baseline CRP, with greater magnitude of response in patients with more elevated CRP.

Keywords: DMARDs (biologic); ankylosing spondylitis; cytokine; inflammation; spondyloarthritis.

Conflict of interest statement

Competing interests: JB has received research grant from AbbVie, Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Medac, MSD, Mundipharma, Novartis, Pfizer, Roche, Sanofi-Aventis, and UCB, and served as consultant or paid speaker for AbbVie, Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Medac, MSD, Mundipharma, Novartis, Pfizer, Roche, Sanofi-Aventis, and UCB. AD has received research grants from AbbVie, Amgen, Eli Lilly, GSK, Janssen, Novartis, Pfizer and UCB, and has received honorarium for serving on the advisory boards of Eli Lilly, Janssen, Novartis, Pfizer and UCB. RL has received research grant from Abbott, Amgen, Centocor, Novartis, Pfizer, Roche, Schering-Plough, UCB, and Wyeth, served as consultant for AbbVie, Ablynx, Amgen, Astra-Zeneca, Bristol-Myers Squibb, Centocor, GSK, Novartis, Merck, Pfizer, Roche, Schering-Plough, UCB, and Wyeth, and paid speaker for Abbott, Amgen, Bristol-Myers Squibb, Centocor, Merck, Pfizer, Roche, Schering-Plough, UCB, Wyeth. XB has received research grant from AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB, and Werfen, served as consultant or paid speaker for AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB, and Werfen. CMR has received research grant from AbbVie, Bristol-Myers Squibb, Novartis, Merck, Pfizer, and Wyeth, served as consultant for Pfizer, Roche, UCB, Wyeth, and Merck, and paid speaker for Abbott, Bristol-Myers Squibb, Merck, Pfizer, Roche, Schering-Plough, and Wyeth. JS has received research grant from AbbVie, Pfizer, and Merck, served as consultant for AbbVie, Pfizer, Merck, UCB, and Novartis, and paid speaker for AbbVie, Pfier, Merck, and UCB. EQF is an employee of Novartis. RM, BP, KKG are employees of Novartis and own Novartis stock. DVH served as consultant for AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos, Gilead, GSK, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB.

Figures

Figure 1

Improvement in (A) ASAS20 and (B) ASAS40 response rates in patients with normal or elevated CRP at baseline through week 156. *p†p<0.001; §p<0.01; ‡p<0.05 vs placebo; missing values were imputed as non-response through week 16. MI presented from week 20 to 156 (shaded area) included n=56 and 103 in the normal baseline CRP and elevated baseline CRP groups, respectively. Data for secukinumab 150 mg and placebo at week 16, and for secukinumab 150 mg at week 156 are depicted. ASAS, Assessment of SpondyloArthritis international Society criteria; CRP, C-reactive protein; MI, multiple imputation; N, number of patients with available baseline CRP (normal or elevated) included in this pooled study through week 16; n, number of patients in this pooled study from week 20 to 156.

Figure 2

Improvement in BASDAI score in patients with normal or elevated CRP at baseline through week 156. *p†p<0.001; vs placebo; MMRM data shown through week 156. From week 20 to 156 data shown for n=56 and 103 patients in the normal baseline CRP and elevated baseline CRP groups, respectively. Data for secukinumab 150 mg and placebo at week 16, and for secukinumab 150 mg at week 156 are depicted. BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; CRP, C-reactive protein; MMRM, mixed-effect model repeated measure; N, number of patients with available baseline CRP (normal or elevated) included in this pooled study through week 16; n, number of patients in this pooled study from week 20 to 156.

Figure 3

Percent of patients with ASDAS inactive disease grouped by normal or elevated CRP at baseline through week 156. §p<0.01; ‡p<0.05 vs placebo; missing values were imputed as non-response through week 16. MI presented from week 20 to 156 (shaded area) included n=56 and 103 in the normal baseline CRP and elevated baseline CRP groups, respectively. Data for secukinumab 150 mg and placebo at week 16 and for secukinumab 150 mg at week 156 are depicted. ASDAS, Ankylosing Spondylitis Disease Activity Score; CRP, C-reactive protein; MI, multiple imputation; N, number of patients with available baseline CRP (normal or elevated) included in this pooled study through week 16; n, number of patients in this pooled study from week 20 to 156.