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ObjectivesTo define the instruments for the Assessment of SpondyloArthritis international Society–Outcomes Measures in Rheumatology (ASAS-OMERACT) core domain set for axial spondyloarthritis (axSpA).MethodsAn international working group representing key stakeholders selected the core outcome instruments following a predefined process: (1) identifying candidate instruments using a systematic literature review; (2) reducing the list of candidate instruments by the working group, (3) assessing the instruments’ psychometric properties following OMERACT filter 2.2, (4) selection of the core instruments by the working group and (5) voting and endorsement by ASAS.ResultsThe updated core set for axSpA includes seven instruments for the domains that are mandatory for all trials: Ankylosing Spondylitis Disease Activity Score and Numerical Rate Scale (NRS) patient global assessment of disease activity, NRS total back pain, average NRS of duration and severity of morning stiffness, NRS fatigue, Bath Ankylosing Spondylitis Function Index and ASAS Health Index. There are 9 additional instruments considered mandatory for disease-modifying antirheumatic drugs (DMARDs) trials: MRI activity Spondyloarthritis Research Consortium of Canada (SPARCC) sacroiliac joints and SPARCC spine, uveitis, inflammatory bowel disease and psoriasis assessed as recommended by ASAS, 44 swollen joint count, Maastricht Ankylosing Spondylitis Enthesitis Score, dactylitis count and modified Stoke Ankylosing Spondylitis Spinal Score. The imaging outcomes are considered mandatory to be included in at least one trial for a drug tested for properties of DMARD. Furthermore, 11 additional instruments were also endorsed by ASAS, which can be used in axSpA trials on top of the core instruments.ConclusionsThe selection of the instruments for the ASAS-OMERACT core domain set completes the update of the core outcome set for axSpA, which should be used in all trials.

The impact of the COVID-19 pandemic on patients with inflammatory rheumatic diseases, such as ankylosing spondylitis (AS), has been variable. Here, we assess disease activity and health-related quality of life (HRQoL) through the pandemic in patients with AS.In the open-label extension (OLE) of the phase 2b BE AGILE study, patients with AS received 160 mg of subcutaneous bimekizumab every 4 weeks. We assessed Ankylosing Spondylitis Disease Activity Score with C-reactive protein (ASDAS-CRP), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Quality of Life (ASQoL) scores in the OLE immediately before and during the COVID-19 pandemic (September 2019 to April 2021).A total of 232 patients remained in the BE AGILE OLE and were included in this post hoc study at the start of the analysis period (September 1, 2019); 12 patients had a COVID-19 treatment-emergent adverse event, and no cases resulted in death. The number of missed bimekizumab doses due to COVID-19 (11 doses) was minimal, and missed assessments remained low (≤5%) compared with the prepandemic period. Mean ASDAS-CRP (1.8), BASDAI (2.4), and ASQoL scores (2.8) in the OLE were low at pre-pandemic baseline and remained stable at 1.7 to 1.8, 2.2 to 2.4, and 2.0 to 2.8, respectively, across successive 3-month periods immediately before and during the pandemic. ASDAS-CRP, BASDAI, and ASQoL stability was consistent across major study countries.Disease activity and HRQoL remained stable during the COVID-19 pandemic in patients with AS receiving bimekizumab in the BE AGILE OLE, with no indication of negative effects on these outcomes.

Objective Tumor necrosis factor inhibitors (TNFi) are an effective treatment for non-radiographic axial spondyloarthritis (nr-axSpA). To be eligible, however, many authorities require patients with nr-axSpA to show active sacroiliitis on magnetic resonance imaging (MRI) and/or an elevated C-reactive protein (CRP) level, possibly resulting in a perception that patients with nr-axSpA without both factors have only low responses to TNFi treatment. We evaluated clinical responses to certolizumab pegol (CZP) in patients with nr-axSpA stratified by baseline MRI/CRP status. Methods C-axSpAnd was a phase 3, multicenter study on CZP in adult patients with active nr-axSpA and objective signs of inflammation. This analysis assessed efficacy of CZP over the 52-week randomized, double-blind, placebo-controlled period in patients stratified into subgroups based on the presence of active sacroiliitis on MRI and CRP level at baseline. Results CZP-treated patients across all MRI/CRP subgroups achieved clinical responses greater than placebo. Across outcome measures, CZP-treated MRI+/CRP+ patients demonstrated the greatest clinical responses, but substantial improvements were also observed in CZP-treated MRI+/CRP- and MRI-/CRP+ patients. Ankylosing Spondylitis Disease Activity Score Major Improvement response rates at week 52 among CZP-treated patients (75.6% MRI+/CRP+; 47.5% MRI-/CRP+; and 29.7% MRI+/CRP-) were higher than rates in placebo groups (range: 3.9%-12.5%). Assessment of SpondyloArthritis international Society 40% response, Bath Ankylosing Spondylitis Disease Activity Index, and Bath Ankylosing Spondyloarthritis Functional Index had similar response patterns, although differences between the CZP-treated MRI/CRP subgroups were smaller. Clinical responses among CZP-treated patients were also observed in additional subgroups, including those with low Spondyloarthritis Research Consortium of Canada MRI sacroiliac joint inflammation scores and those with normal baseline CRP levels. Conclusion Our findings indicate that CZP treatment benefits patients with nr-axSpA across MRI+/CRP+, MRI-/CRP+, and MRI+/CRP- subgroups.

Nonradiographic axial spondyloarthritis (nr-axSpA) represents a distinct phenotype within the spectrum of axial spondyloarthritis (axSpA), which is characterized by a range of clinical manifestations. Despite a high disease burden that is comparable to ankylosing spondylitis (also known as radiographic axSpA), there is an unmet need to recognize and effectively manage patients with active nr-axSpA.A targeted literature search was conducted in OVID (MEDLINE and Embase databases) to identify articles on nr-axSpA, including its definition, demographics, epidemiology, burden, diagnosis, clinical presentation, and treatment guidelines.The lack of adequate epidemiological data and incomplete understanding of nr-axSpA among rheumatologists and nonrheumatologists contributes to delayed referrals and diagnosis. This delay results in a substantial burden on patients, physically and psychologically, and the healthcare system. Targeted therapies, such as biologics, including inhibitors of tumor necrosis factor or interleukin-17A, have been approved and utilized for the management of nr-axSpA, and other novel therapeutics with different mechanisms of action are in development. Raising awareness among US internists regarding the prevalence of nr-axSpA, disease burden, clinical presentation, diagnostic tools, and available treatments is important for improved disease management.Future clinical investigations focusing on the development of markers that aid early diagnosis and predict treatment response may also improve the management of nr-axSpA. This review provides an overview of nr-axSpA with the aim of raising awareness of the disease among US internists, with an overarching goal to contribute toward the improved recognition and timely referral of these patients to rheumatologists for diagnosis and management.

Objectives Fat lesions (FLs) on MRI T1 sequences are considered to be early indicators of structural spinal progression in axial spondyloarthritis (axSpA) patients. In this post-hoc analysis from RAPID-axSpA, we assess whether tumour necrosis factor inhibitor (TNFi) treatment over 4 years impacts FLs in spinal vertebral edges (VEs) of patients with axSpA. Methods In RAPID-axSpA (NCT01087762), a 4-year, phase 3 randomized trial, participants were randomized to certolizumab pegol (CZP; 400 mg loading dose at Weeks 0/2/4 then 200/400 mg every 2/4 weeks) or placebo (PBO) at baseline; PBO-randomized participants switched to CZP at Week 16/24 (denoted PBO-randomized/CZP). Spinal MRI scans were taken at Weeks 0, 12, 48, 96 and 204. Changes in proportions of VEs with FLs are reported as odds ratios (ORs) between time points. Results Overall, 136 participants (CZP: 89, PBO-randomized/CZP: 47) had a baseline and ≥1 post-baseline MRI. The OR (95% confidence interval) vs baseline of FLs was higher in PBO-randomized/CZP vs CZP-randomized participants at Weeks 48 [3.35 (2.16–5.19) vs 1.45 (1.07–1.97)], 96 [2.62 (1.77–3.88) vs 1.84 (1.36–2.48)] and 204 [2.55 (1.59–4.06) vs 1.71 (1.23–2.37)]. Across 204 weeks, FLs increased more in VEs with baseline inflammation [Week 204 OR: 4.84 (2.56–9.18)] than those without [OR: 1.15 (0.78–1.71)]. VEs in which inflammation was resolved by Week 12 had lower FL prevalence at Weeks 48, 96 and 204 compared with VEs with unresolved inflammation. Conclusions Early and sustained suppression of inflammation mitigates the risk of long-term FL development in the spine in study participants with axSpA evaluated over 4 years. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov, NCT01087762.

Author(s): Deodhar, Atul; Gensler, Lianne S; Kay, Jonathan; Maksymowych, Walter P; Haroon, Nigil; Landewe, Robert; Rudwaleit, Martin; Hall, Stephen; Bauer, Lars; Hoepken, Bengt; de Peyrecave, Natasha; Kilgallen, Brian; van der Heijde, Desiree | Abstract: ObjectiveThe natural history of nonradiographic axial spondyloarthritis (SpA) is incompletely characterized, and there are concerns that nonsteroidal antiinflammatory drugs provide inadequate disease control in patients with active disease. This study was undertaken to investigate the effects of certolizumab pegol (CZP), an anti-tumor necrosis factor treatment, in patients with nonradiographic axial SpA with objective signs of inflammation.MethodsIn this ongoing parallel-group double-blind study, adults with active disease were recruited from 80 centers in Australia, Europe, North America, and Taiwan, and were randomized 1:1 to receive placebo or CZP (400 mg at weeks 0, 2, and 4, followed by 200 mg every 2 weeks) in addition to nonbiologic background medication (NBBM). Switching to open-label CZP (or other biologic) or making background medication changes was permitted at any point during the trial, although changes before week 12 were discouraged. The primary end point was the proportion of patients achieving major improvement (MI) (i.e., a ≥2.0-point decrease in the score from baseline or achievement of the lowest possible score [0.6]) in the Ankylosing Spondylitis Disease Activity Score (ASDAS) at week 52.ResultsA total of 317 patients were randomized to receive placebo plus NBBM (n = 158) or CZP plus NBBM (n = 159). ASDAS-MI at week 52 was achieved in 47.2% (75 of 159) of CZP plus NBBM patients, which was significantly greater (P l 0.0001) than the 7.0% (11 of 158) of placebo plus NBBM patients in whom ASDAS-MI was achieved. Of the placebo plus NBBM patients, 60.8% (96 of 158) switched to open-label treatment before week 52 compared to 12.6% (20 of 159) of the CZP plus NBBM patients.ConclusionAdding CZP to background medication is superior to adding placebo in patients with active nonradiographic axial SpA. These results indicate that remission in nonradiographic axial SpA treated without biologics occurs infrequently, demonstrating the need for treatment beyond nonbiologic therapy.

Introduction Achievement of remission is a key treatment goal for patients with axial spondyloarthritis (axSpA). C-OPTIMISE assessed achievement of sustained clinical remission in patients with axSpA, including radiographic (r) and non-radiographic (nr) axSpA, during certolizumab pegol (CZP) treatment, and subsequent maintenance of remission following CZP dose continuation, dose reduction or withdrawal. Here, we report outcomes from the first 48 weeks (induction period) of C-OPTIMISE, during which patients received open-label CZP. Methods C-OPTIMISE (NCT02505542) was a two-part, multicenter, phase 3b study in adult patients with early axSpA (r-/nr-axSpA), including a 48-week open-label induction period followed by a 48-week maintenance period. Patients with active adult-onset axSpA

Background Certolizumab pegol (CZP) treatment has demonstrated improvements in multiple manifestations of non-radiographic axial spondyloarthritis (nr-axSpA), including patient-reported outcomes (PROs). Here, we report PROs for nr-axSpA patients treated with CZP or placebo in CaxSpAnd - the first 52-week placebo-controlled study to investigate the efficacy of an anti-TNF agent in patients with active nr-axSpA and objective signs of inflammation. Methods C-axSpAnd (NCT02552212) is a 3-year, phase 3, multicenter study including a 52-week double-blind, placebo-controlled period (completed); patients who had an inadequate response to ≥ 2 non-steroidal anti-inflammatory drugs were randomized 1:1 to placebo or CZP (400mg at Weeks 0/2/4, then 200mg every 2 weeks). Clinical PROs included: Sleep Problems Index scores I (6 items) and II (9 items) from the Medical Outcomes Study Sleep Scale (assesses sleep disturbance, adequacy, somnolence, quantity, snoring, and awakening short of breath or with a headache), nocturnal spinal pain (numerical rating scale [NRS]), fatigue (BASDAI Q1), and morning stiffness (average of BASDAI Q5 + 6). Post-hoc analyses of minimal clinically important differences (MCID [≥1-point improvement]) for fatigue and nocturnal spinal pain were conducted. Variables were analyzed using an ANCOVA model including baseline score as a covariate and fixed effects for treatment group, region and MRI/CRP classification. P-values were nominal. Missing values following discontinuation of double-blind treatment were imputed using last observation carried forward. Results 317 patients with nr-axSpA were randomised to CZP (n = 159) or placebo (n = 158); 125 (79%) and 54 (34%) patients, respectively, completed Week 52. CZP-treated patients showed greater improvements (indicated by higher scores) in Sleep Problems Index II scores vs placebo-treated patients at Week 12 (mean change from baseline: 4.8 [CZP] vs 2.2 [placebo]; p < 0.001). Improvements were also seen in other clinical PROs (Table). By Week 12, greater proportions of patients treated with CZP vs placebo experienced at least MCID response in fatigue (85.4% vs 57.6%, respectively) and nocturnal spinal pain (82.8% vs 58.9%, respectively); results were sustained through Week 52. Conclusion CZP-treated nr-axSpA patients showed substantial improvements in sleep quality and other clinical outcomes important to patients; future analyses of these data will explore associations between sleep quality and other clinical PROs. Disclosures R. Sengupta: Other; R.S. has received speaker fees, support for conference attendance and grants from Abbvie, Biogen, Celgene, Novartis, Pfizer and UCB Pharma. L. Gensler: Grants/research support; AbbVie, Amgen, Novartis, UCB Pharma; consulting fees from Galapagos, Eli Lilly and Janssen. J. Kay: Consultancies; AbbVie, Boehringer Ingelheim, Celltrion Healthcare, Horizon Therapeutics, Merck Sharp & Dohme, MorphoSys, Novartis, Pfizer, Samsung Bioepis, Sandoz and UCB Pharma. Grants/research support; Gilead Sciences, Novartis AG, Pfizer and UCB Pharma. W. Maksymowych: Other; Consultant and/or speaker fees and/or grants from AbbVie, Amgen, Eli Lilly, Janssen, Merck, Pfizer, Synarc, Sanofi and UCB Pharma. N. Haroon: Consultancies; Abbvie, Amgen, Eli Lilly, Janssen, Novartis and UCB Pharma. L. Bauer: Other; Employee of UCB Pharma. B. Hoepken: Other; Employee of UCB Pharma. N. de Peyrecave: Other; Employee of UCB Pharma. T. Kumke: Other; Employee of UCB Pharma. A. Deodhar: Consultancies; AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Glaxo Smith and Klein, Janssen, Novartis, Pfizer and UCB. Grants/research support; BMS, Eli Lilly, Glaxo Smith & Kline, Janssen, Novartis, Pfizer and UCB.

Background Certolizumab pegol (CZP) treatment has been shown to significantly improve work and household productivity and social participation compared to placebo in active non-radiographic axial spondyloarthritis (nr-axSpA) patients up to 24 weeks. Here, we report the impact of CZP in combination with non-biologic background medication (NBBM) on signs and symptoms of nr-axSpA compared to placebo+NBBM. Methods C-axSpAnd (NCT02552212) is a 3-year, phase 3, multicentre study including a 52-week double-blind, placebo-controlled period (completed). Patients had active nr-axSpA, objective signs of inflammation (OSI; elevated CRP and/or positive MRI of the sacroiliac joint), previous inadequate response to ≥ 2 NSAIDs and were randomised 1:1 to CZP (400 mg at Weeks 0/2/4, then 200 mg every 2 weeks) or placebo. The validated arthritis-specific Work Productivity Survey (WPS) assessed the impact of nr-axSpA on work and household productivity and social participation. Missing data were imputed using last observation carried forward (LOCF) post hoc in the Full Analysis Set (randomised patients who received ≥1 dose of CZP). Results 317 patients were randomised (CZP: 159; placebo: 158). Mean age at baseline was 37.3 years and 51.4% of patients were female. At baseline, most patients were employed (CZP: 124 [77.8%]; placebo: 123 [78.0%]) and reported a mean 3.7 (CZP) and 3.5 (placebo) workdays missed per month due to disease (Table 1). By Week 12, work absenteeism substantially improved in the CZP group compared with placebo (0.9 vs 2.1 days missed per month, LOCF), with further improvements at Week 52 (0.3 vs 2.0 days missed per month, LOCF). Between Week 12 and Week 52, most placebo patients (104, 65.8%) switched to open-label CZP, impacting Week 52 imputed outcomes. Despite this, similar patterns of improvement following CZP treatment were seen for absenteeism, workdays with impaired productivity, household days with missed/reduced productivity and social participation between imputed and observed case data (Table 1). Improvements were similar between male and female patients (data not shown). Conclusion CZP treatment resulted in improvements in work and household productivity and social participation for nr-axSpA patients as early as Week 12 compared to background medication only, with benefits maintained to Week 52. Disclosures K. Gaffney: Other; Research Grants/Consultancy Fees from Abbvie, Biogen, Celgene, Gilead, Izana, Janssen, Lilly, Novartis, Pfizer, UCB Pharma. A. Deodhar: Consultancies; AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Glaxo Smith and Klein, Janssen, Novartis, Pfizer and UCB. Grants/research support; BMS, Eli Lilly, Glaxo Smith & Kline, Janssen, Novartis, Pfizer and UCB. L. Gensler: Consultancies; Galapagos, Eli Lilly and Janssen. Grants/research support; AbbVie, Amgen, Novartis, UCB Pharma. J. Kay: Consultancies; AbbVie, Boehringer Ingelheim, Celltrion Healthcare, Horizon Therapeutics, Merck Sharp & Dohme, MorphoSys, Novartis, Pfizer, Samsung Bioepis, Sandoz and UCB Pharma. Grants/research support; Gilead Sciences, Novartis AG, Pfizer and UCB Pharma. W. Maksymowych: Other; Consultant and/or speaker fees and/or grants from AbbVie, Amgen, Eli Lilly, Janssen, Merck, Pfizer, Synarc, Sanofi and UCB Pharma. N. Haroon: Consultancies; Abbvie, Amgen, Eli Lilly, Janssen, Novartis and UCB Pharma. R. Landewé: Consultancies; Abbott, Ablynx, Amgen, Astra-Zeneca, Bristol Myers Squibb, Centocor, GlaxoSmithKline, Novartis, Merck, Pfizer, Roche, Schering-Plough, UCB Pharma, Wyeth. Member of speakers’ bureau; Abbott, Amgen, Bristol Myers Squibb, Centocor, Merck, Pfizer, Roche, Schering-Plough, UCB Pharma, Wyeth. Grants/research support; Abbott, Amgen, Centocor, Novartis, Pfizer, Roche, Schering-Plough, UCB Pharma, Wyeth. M. Rudwaleit: Consultancies; Abbott, Bristol-Myers Squibb, Janssen, MSD, Pfizer, Roche, UCB Pharma. S. Hall: Other; Consulting fees/ research grants from AbbVie, Eli Lilly, Novartis, and UCB Pharma. L. Bauer: Other; Employee of UCB Pharma. B. Hoepken: Other; Employee of UCB Pharma. N. de Peyrecave: Other; Employee of UCB Pharma. T. Kumke: Other; Employee of UCB Pharma. D. van der Heijde: Consultancies; AbbVie, Amgen, Astellas, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, and UCB. Other; Director of Imaging Rheumatology BV.

BackgroundThe best strategy for maintaining clinical remission in patients with axial spondyloarthritis (axSpA) has not been defined. C-OPTIMISE compared dose continuation, reduction and withdrawal of the tumour necrosis factor inhibitor certolizumab pegol (CZP) following achievement of sustained remission in patients with early axSpA.MethodsC-OPTIMISE was a two-part, multicentre phase 3b study in adults with early active axSpA (radiographic or non-radiographic). During the 48-week open-label induction period, patients received CZP 200 mg every 2 weeks (Q2W). At Week 48, patients in sustained remission (Ankylosing Spondylitis Disease Activity Score (ASDAS) 3.5 at any time point) during the double-blind period.ResultsAt Week 48, 43.9% (323/736) patients achieved sustained remission, of whom 313 were randomised to CZP full maintenance dose, CZP reduced maintenance dose or placebo. During Weeks 48 to 96, 83.7% (87/104), 79.0% (83/105) and 20.2% (21/104) of patients receiving the full maintenance dose, reduced maintenance dose or placebo, respectively, were flare-free (pConclusionsPatients with early axSpA who achieve sustained remission at 48 weeks can reduce their CZP maintenance dose; however, treatment should not be completely discontinued due to the high risk of flare following CZP withdrawal.Trial registration numberNCT02505542, ClinicalTrials.gov.

ObjectivesTo report 4-year imaging outcomes in the RAPID-axSpA (NCT01087762) study of patients with ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA), treated with certolizumab pegol (CZP).MethodsThis phase III, randomised trial was placebo-controlled and double-blind to week 24, dose-blind to week 48 and open-label to week 204. Patients fulfilling the Assessment of Spondyloarthritis International Society (ASAS) axSpA criteria with active disease were stratified (AS/nr-axSpA) according to the modified New York (mNY) criteria at randomisation. Spinal radiographs were assessed using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). MRI inflammation used the Spondyloarthritis Research Consortium of Canada (SPARCC) score for sacroiliac joints (SIJ) and the Berlin spinal score (remission defined as SPARCC ResultsMRI improvements from baseline (BL) to week 12 were maintained to week 204 (SPARCC BL: AS=8.5, nr-axSpA=7.5; SPARCC week 204: AS=1.3, nr-axSpA=2.4; Berlin BL: AS=7.4, nr-axSpA=4.4; Berlin week 204: AS=2.6, nr-axSpA=1.9). 66.7% of patients with AS and 69.6% of patients with nr-axSpA with BL SPARCC scores ≥2, and 65.4% of patients with AS and 57.3% of patients with nr-axSpA with BL Berlin score >2, achieved remission at week 204. Mean mSASSS change in AS from BL to week 204 was 0.98 (95% CI 0.34, 1.63); 0.67 (95% CI 0.21,1.13) from BL to week 96; and 0.31 (95% CI 0.02,0.60) from week 96 to week 204. Corresponding nr-axSpA changes were 0.06 (95% CI −0.17,0.28), –0.01 (95% CI −0.19,0.17) and 0.07 (95% CI −0.07,0.20). 4.5% of patients with nr-axSpA fulfilled the mNY criteria at week 204, while 4.3% of patients with AS no longer did so.ConclusionsIn patients with CZP-treated axSpA, rapid decreases in spinal and SIJ MRI inflammation were maintained to week 204. Overall, 4-year spinal progression was low, with less progression during years 2–4 than 0–2. Radiographic SIJ grading changes demonstrated limited progression.Trial registration numberNCT01087762; Post-results.

We thank Dr Babaoglu for his question about our manuscript entitled ‘Limited Radiographic Progression and Sustained Reductions in MRI Inflammation in Patients with Axial Spondyloarthritis: Four-Year Imaging Outcomes from the RAPID-axSpA Phase 3 Randomised Trial.’1 2 In his response, he refers to an apparent discrepancy between information in the main manuscript and supplemental material. He is correct …

Background In patients (pts) with axial spondyloarthritis (axSpA), inflammation of the spine is believed to trigger a repair mechanism that results in syndesmophyte formation.1Fatty lesions (FLs) in the bone marrow and erosions in the axial skeleton, both visible on magnetic resonance imaging (MRI) T1 sequences, are post–inflammatory changes that have been shown to contribute significantly to models predicting new bone formation.2 It has previously been shown that resolution of inflammatory lesions (INFLs) in pts with axSpA treated with anti–TNF therapy may be associated with an increase in FLs.3,4 RAPID–axSpA was a long–term study in pts with radiographic (r)–axSpA (also known as ankylosing spondylitis) or non–radiographic (nr)–axSpA treated with certolizumab pegol (CZP), which rapidly suppressed active inflammation of the spine, with pts showing limited spinal radiographic progression over 4 years.5 However, it is not known whether CZP treatment coincides with changes in FLs, sclerosis, and erosions. Objectives To report the incidence and association of active inflammation and chronic lesions in the spine of pts with axSpA treated with CZP over 4 years Methods RAPID–axSpA (NCT01087762) was double–blind and placebo (PBO)–controlled to Week (Wk)24, dose–blind to Wk48, and open–label to Wk204. CZP–randomised pts (either 200mg every 2 weeks [Q2W] or 400 mg Q4W) continued their assigned dose throughout; PBO–randomised pts received CZP from Wk24, or if non–responders, from Wk16 onwards. Blinded spinal MRI scans at baseline (BL) and Wk12, 48, 96, and 204 were assessed by 2 central readers to evaluate the presence/absence of active INFLs (Short T1 Inversion Recovery [STIR] sequence) and FLs, sclerosis and erosions (T1 sequence) in vertebral edges (VEs) (present if recorded so by both readers). Pts (r–axSpA and nr–axSpA combined) with valid assessments at BL and at least once post–BL were included. Mean lesion counts at the pt level were estimated from mixed models with repeated measures (MMRM), fitted on observed data from CZP–randomised pts. Associations between INFLs and FLs at the VE level for CZP–and PBO–randomised pts were described using cross–tabulations. Results Of 325 randomised pts, 136 were eligible for these analyses. In pts randomised to CZP at Wk0 (n=89), active INFLs were reduced, and FL counts only slightly increased by Wk12; both were sustained at a low level to Wk204 (Table A). Very few VEs with sclerosis and erosions were observed at BL, and no changes in their frequency were observed over 4 years’ treatment (Table A). Over 4 years’ CZP treatment, the risk of developing a new FL was greater in VEs with vs without INFLs at BL, regardless of changes to INFLs in these VEs post–BL (Table B). The prevalence of FLs was greater in pts with >3 vs ≤3 years’ symptom duration and there were more new FLs in the >3 years subgroup during CZP treatment (data not shown) Conclusion Long–term CZP treatment in axSpA pts was associated with rapid and sustained reduction in active inflammation and a negligible increase in FLs in VEs. More FLs developed in VEs with INFLs at BL than without, but this was not affected by resolution of INFLs. There was no increase in sclerosis and erosions in VEs over 4 years’ CZP treatment. Reference: [1] Appel H. Curr Rheumatol Rep2008;10:356–63; 2. Poddubnyy D. Arthritis Rheum 2016;68:1899–903; 3. Maksymowych W. Ann Rheum Dis 2013;72:23–8; 4. Song I. Ann Rheum Dis 2011;70:1257–63; 5. van der Heijde D. Ann Rheum Dis2018;77:699–705. Acknowledgement We thank the patients who participated. This study was funded by UCB Pharma, medical writing by Hinal Tanna, Costello Medical, UK. Disclosure of Interests Xenofon Baraliakos Grant/research support from: AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Chugai, Janssen, MSD, Novartis, Pfizer Inc, Roche and UCB, Grant/research support from: AbbVie, Pfizer, Merck Sharp & Dohme, UCB Pharma, Novartis, Consultant for: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Chugai, Janssen Biologics, Novartis, Pfizer, UCB Pharma, Galapagos, Speakers bureau: AbbVie, Chugai, Janssen, Novartis, Pfizer, UCB Pharma, Sebastian Kruse: None declared, Simone Auteri Employee of: Employee of UCB Pharma, Natasha de Peyrecave Employee of: Employee of UCB Pharma, Tommi Nurminen Employee of: Employee of UCB Pharma, Thomas Kumke Employee of: UCB Pharma, Bengt Hoepken Employee of: Employee of UCB Pharma, Juergen Braun Shareholder of: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB, Grant/research support from: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB, Grant/research support from: Abbott, Bristol Myers Squibb, Celgene, Celltrion, Chugai, Johnson & Johnson, MSD, Novartis, Pfizer, Roche, UCB Pharma, Grant/research support from: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB, Grant/research support from: Abbvie (Abbott), Amgen, Baxter, Biogen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, Hexal, Janssen, Lilly, Medac, MSD (Schering-Plough), Mylan, Mundipharma, Novartis, Pfizer (Wyeth, Hospira), Roche, Sanofi-Aventis and UCB, Consultant for: Abbvie (Abbott), Amgen, Baxter, Biogen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, Hexal, Janssen, Lilly, Medac, MSD (Schering-Plough), Mylan, Mundipharma, Novartis, Pfizer (Wyeth, Hospira), Roche, Sanofi-Aventis and UCB, Consultant for: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB, Consultant for: Abbott, Bristol Myers Squibb, Celgene, Celltrion, Chugai, Johnson & Johnson, MSD, Novartis, Pfizer, Roche, UCB Pharma, Speakers bureau: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB, Speakers bureau: Abbvie (Abbott), Amgen, Baxter, Biogen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, Hexal, Janssen, Lilly, Medac, MSD (Schering-Plough), Mylan, Mundipharma, Novartis, Pfizer (Wyeth, Hospira), Roche, Sanofi-Aventis and UCB, Speakers bureau: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB

Background C-OPTIMISE is the first trial to evaluate whether certolizumab pegol (CZP) can be reduced/discontinued in patients with radiographic(r)-axSpA/ankylosing spondylitis (AS) and non-radiographic(nr)-axSpA achieving sustained remission after 48 weeks’ (wks’) treatment. Objectives Here, we report interim efficacy and safety data for both subpopulations from the ongoing trial. Methods Up to Wk48, C-OPTIMISE (NCT02505542) was open-label (Part A), followed by 48-wk parallel-group, double-blind, placebo-controlled treatment (full dose and half dose) to Wk96 (Part B). Patients with adult-onset axSpA of Results Part A: Of 736 patients (Table A), 43.9% achieved sustained remission (r-axSpA/AS: 42.8%; nr-axSpA: 45.3%; NRI). At baseline, 98.5% patients had high/very high disease activity (ASDAS≥2.1); at Wk48, 52.7% (r-axSpA/AS: 52.6%; nr-axSpA: 52.9%) had inactive disease (ASDAS Conclusion The run-in phase of C-OPTIMISE shows that similar and substantial proportions of patients with r–axSpA/AS and nr-axSpA achieved sustained remission during 48 wks’ CZP treatment. No new safety signal was identified. Acknowledgement We thank the patients who participated. This study was funded by UCB Pharma, medical writing by Hinal Tanna, Costello Medical, UK. Disclosure of Interests Robert B.M. Landewe: None declared, Desiree van der Heijde Consultant for: AbbVie, Amgen, Astellas, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, Union Chimique Belge, maxime dougados Grant/research support from: Eli Lilly and Company, Pfizer, AbbVie, and UCB Pharma, Consultant for: Eli Lilly and Company, Pfizer, AbbVie, and UCB Pharma, Xenofon Baraliakos Grant/research support from: AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Chugai, Janssen, MSD, Novartis, Pfizer Inc, Roche and UCB, Grant/research support from: AbbVie, Pfizer, Merck Sharp & Dohme, UCB Pharma, Novartis, Consultant for: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Chugai, Janssen Biologics, Novartis, Pfizer, UCB Pharma, Galapagos, Speakers bureau: AbbVie, Chugai, Janssen, Novartis, Pfizer, UCB Pharma, Filip van den Bosch Consultant for: AbbVie, BMS, Galapagos, Janssen, Lilly, Merck, Novartis, Pfizer and UCB, Speakers bureau: AbbVie, BMS, Janssen, Lilly, Merck, Novartis, Pfizer and UCB., Karl Gaffney Grant/research support from: Abbvie, Pfizer, Consultant for: Abbvie, Lilly, Novartis, UCB, Speakers bureau: Abbvie, Biogen, Gilead, Lilly, Novartis, UCB, Natasha de Peyrecave Employee of: Employee of UCB Pharma, Lars Bauer Employee of: Employee of UCB Pharma, Bengt Hoepken Employee of: Employee of UCB Pharma, Karen Thomas Employee of: Contracted Statistician of UCB Pharma., Lianne S. Gensler Grant/research support from: Abbvie, Amgen, UCB Pharma, Consultant for: Novartis, Lilly, Janssen