Secukinumab efficacy on resolution of enthesitis in psoriatic arthritis: pooled analysis of two phase 3 studies

Abstract

Background: Enthesitis is one of the psoriatic arthritis (PsA) domains. Patients with enthesitis are associated with worse outcomes than those without enthesitis. The effect of secukinumab on the resolution of enthesitis in patients with PsA was explored using pooled data from the FUTURE 2 and 3 studies.

Method: Assessments of enthesitis through week 104 used the Leeds Enthesitis Index. These post hoc analyses included resolution of enthesitis count (EC = 0), median time to first resolution of enthesitis (Kaplan-Meϊer estimate), and shift analysis (as observed) of baseline EC (1, 2, or 3-6) to full resolution (FR), stable (similar or reduction of EC), or worse (EC > baseline). Efficacy outcomes (ACR, PASI, HAQ-DI, SF-36 PCS, and DAS28-CRP) were assessed in patients with or without baseline enthesitis. Results are reported for secukinumab 300 and 150 mg in the overall population and by prior TNFi treatment.

Results: A total of 65% (466/712) of patients had baseline enthesitis. In the overall population, FR was achieved as early as week 16 in 65% (300 mg) and 56% (150 mg) versus 44% (placebo) patients, with further improvements to 91% (300 mg) and 88% (150 mg) at week 104. The majority (89%) of patients without enthesitis at baseline maintained this status at week 104. Median days to resolution of EC were shorter with secukinumab 300 and 150 mg versus placebo (57 and 85 vs 167 days, respectively). In patients with EC of 1 or 2, shift analysis from baseline to week 24 showed that more patients achieved FR with secukinumab 300 mg and 150 mg versus placebo, whereas no difference between secukinumab and placebo was shown in the more severe patients with EC of 3-6. Increases in proportions of patients with FR were observed with secukinumab irrespective of the severity of EC from baseline to week 104. Improvements in efficacy outcomes were similar in patients with or without enthesitis treated with secukinumab 300 mg.

Conclusion: Secukinumab provided early and sustained resolution of enthesitis in patients with PsA over 2 years. Secukinumab 300 mg provided higher resolution than 150 mg in patients with more severe baseline EC and showed similar overall efficacy in patients with or without enthesitis.

Trial registration: FUTURE 2: ClinicalTrials.gov, NCT01752634 (date of study registration: December 19, 2012), and EudraCT, 2012-004439-22 (date of study registration: December 12, 2012) FUTURE 3: ClinicalTrials.gov, NCT01989468 (date of study registration: November 21, 2013), and EudraCT, 2013-004002-25 (date of study registration: December 17, 2013).

Keywords: Anti-TNF; Biologics; Enthesitis; Interleukin 17A inhibitor; Psoriatic arthritis; Secukinumab.

Conflict of interest statement

LC Coates: Grant/research support from AbbVie, Pfizer, Novartis, Lilly, Celgene and Janssen; Consultant for AbbVie, Amgen, Biogen, Boehringer Ingelheim, Celgene, Gilead, Galapagos, Pfizer, UCB, Novartis, Lilly and Janssen

JK Wallman: Consultant for: AbbVie, Celgene, Lilly, Novartis, UCB

D McGonagle: Grant/research support from: Novartis, Janssen, Pfizer, AbbVie, Lilly; Speakers bureau: Novartis, Janssen, Pfizer, AbbVie, Lilly, UCB

G Schett: Grant/research support from: BMS, Celgene, GSK, Lilly, Novartis; Consultant for: AbbVie, BMS, Celgene, Janssen, Lilly, Novartis, UCB; Speakers bureau: AbbVie, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer

IB McInnes: Grant/research support from: AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, UCB; Consultant for: AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, UCB; Speakers bureau: AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, UCB

PJ Mease: Grant/research support from AbbVie, Amgen, BMS, Celgene, Crescendo Bioscience, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer and UCB; Consultant for AbbVie, Amgen, BMS, Celgene, Crescendo Bioscience, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer and UCB; Speakers bureau for AbbVie, Amgen, BMS, Celgene, Crescendo Bioscience, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer and UCB

L Rasouliyan: Consultant for: Novartis through employment at RTI, Employee of: RTI Health Solutions

E Quebe-Fehling: Shareholder and employee of Novartis

DL Asquith: Shareholder and employee of Novartis

AER Fasth: Employee of Novartis

L Pricop: Shareholder and employee of Novartis

C Gaillez: Shareholder and employee of Novartis and Shareholder of BMS

Figures

Fig. 1

Proportion of patients with enthesitis at baseline achieving full resolution over 104 weeks. Data shown for overall population (A), TNFi-naïve (B), and TNFi-IR (C) subpopulations. n, number of patients with enthesitis at baseline. Proportion of patients with resolution at weeks 16, 52, and 104 were based on the survival analysis (Kaplan-Meϊer estimates) at days 112, 365, and 729, respectively. Placebo patients were censored at day 168 of follow-up. EC, enthesitis count; FR, full resolution; IR, inadequate responder; SEC, secukinumab; TNFi, tumor necrosis factor inhibitor

Fig. 2

Time to resolution of enthesitis in patients with enthesitis at baseline. Data shown for overall population (A), TNFi-naïve (B), and TNFi-IR (C) subpopulations. Percentages of patients with resolution at weeks 16, 52, and 104 were derived as 1 minus the survival function at days 112, 365, and 729, respectively (Kaplan-Meϊer plot). Placebo patients were censored at day 168 of follow-up. IR, inadequate responder; SEC, secukinumab; TNFi, tumor necrosis factor inhibitor

Fig. 3

Shift analysis of enthesitis count from baseline to weeks 24, 52, and 104. A, B, and C represents EC = 1, 2, and 3–6 at baseline, respectively. EC 3–6 group includes patients with baseline EC 3, 4, 5, or 6. Shift analysis on resolution of EC from baseline to week 24/52/104 is categorized based on the three criteria of resolution: FR (EC = 0), stable (0 < EC ≤ baseline EC), and worse (> baseline EC). EC, enthesitis count; FR, full resolution; n, number of patients who completed week 24 and had EC available at both baseline and week 24

Fig. 4

Heat map of enthesitis resolution by treatment group through week 104. The asterisk indicate discontinuation due to following reasons: adverse events, death, lack of efficacy, lost to follow-up, non-compliance with study treatment, physician decision, pregnancy, patient/guardian decision, and withdrawal of informed consent. Placebo patients switched therapies at week 16 or 24. All patients with enthesitis at baseline were followed until the end of study or discontinuation. BL, baseline, EC, enthesitis count; W, week

Fig. 5

Change in enthesitis sites with secukinumab 300 mg and 150 mg over week 104 in patients with no enthesitis at baseline. Data presented are as observed. Number of evaluable patients at week 4—90 (300 mg), 78 (150 mg), and 70 (placebo); at week 16—92 (300 mg), 78 (150 mg), and 70 (placebo); and at week 104—83 (300 mg) and 62 (150 mg). ES, enthesitis site; n, number of patients with no enthesitis at weeks 4, 16, and 104