Active Active Ankylosing Spondylitis Research Articles

Tofacitinib Reduces Spinal Inflammation in Vertebral Bodies and Posterolateral Elements in Ankylosing Spondylitis: Results from a Phase 2 Trial.

This post hoc analysis of phase 2 trial data assessed the efficacy of tofacitinib on magnetic resonance imaging (MRI) outcomes with the detailed anatomy-based Canada-Denmark (CANDEN) MRI scoring system and evaluated tofacitinib suppression of spinal inflammation in patients with active ankylosing spondylitis (AS). Patients with active AS (per modified New York criteria) were randomized 1:1:1:1 to receive tofacitinib 2, 5, or 10mg twice daily (BID), or placebo, in a 16-week, phase 2, double-blind clinical trial. Spine MRI assessments were performed at baseline and week 12. For post hoc analysis, MRI images from patients receiving tofacitinib 5 or 10mg BID, or placebo, were re-evaluated by two readers blinded to time point/treatment and assessed by the CANDEN MRI scoring system. Least squares mean changes from baseline to week 12 were reported for CANDEN-specific MRI outcomes, with analysis of covariance used for comparisons of pooled tofacitinib and tofacitinib 5 or 10mg BID versus placebo. p values without multiplicity adjustment were reported. MRI data from 137 patients were analyzed. At week 12, CANDEN spine inflammation score and vertebral body, posterior elements, corner, non-corner, facet joint, and posterolateral inflammation subscores were significantly reduced with pooled tofacitinib versus placebo (p < 0.0001; except non-corner subscore, p < 0.05). Total spine fat score was numerically increased with pooled tofacitinib versus placebo. In patients with AS, tofacitinib treatment was associated with significant reductions in MRI scores of spinal inflammation versus placebo, as assessed by the CANDEN MRI scoring system. Tofacitinib reduced inflammation in posterolateral elements of the spine and facet joints, which has not been described previously. ClinicalTrials.gov registry (NCT01786668).

Upadacitinib (Rinvoq)

&#x0D; CADTH recommends that Rinvoq be reimbursed for the treatment of adults with active ankylosing spondylitis (AS) who have had an inadequate response to a biologic disease-modifying antirheumatic drug (bDMARD) or when use of those therapies is inadvisable only if certain conditions are met.&#x0D; Eligibility for Rinvoq should be based on the criteria used by each of the public drug plans for reimbursement of bDMARDs for the treatment of adult with active AS who have had an inadequate response to a bDMARD, are intolerant, or who have contraindications to bDMARDs.&#x0D; Rinvoq should only be reimbursed if it is prescribed by a rheumatologist. For patients with other manifestations, an ophthalmologist, gastroenterologist, or dermatologist may be consulted. Rinvoq should not be reimbursed when used in combination with bDMARDs or other Janus kinase (JAK) inhibitor treatments for active AS. The cost of Rinvoq should not exceed the drug program cost of treatment with the least expensive bDMARD reimbursed for the treatment of AS.&#x0D;

Efficacy and safety of upadacitinib for active ankylosing spondylitis refractory to biological therapy: a double-blind, randomised, placebo-controlled phase 3 trial

ObjectivesTo evaluate the efficacy and safety of upadacitinib, a Janus kinase inhibitor, in patients with active ankylosing spondylitis (AS) with an inadequate response (IR) to biological disease-modifying antirheumatic drugs (bDMARDs).MethodsAdults...

POS0306 EFFICACY AND SAFETY OF UPADACITINIB IN PATIENTS WITH ACTIVE ANKYLOSING SPONDYLITIS REFRACTORY TO BIOLOGIC THERAPY: A DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED PHASE 3 TRIAL

BackgroundUpadacitinib (UPA) was shown to be safe and effective through 2 years in patients (pts) with active ankylosing spondylitis (AS) naïve to biologic disease-modifying antirheumatic drugs (bDMARDs) in the pivotal phase 2/3 SELECT-AXIS 1 trial.1,2ObjectivesTo assess the efficacy and safety of UPA in pts with active AS with an inadequate response (IR) to bDMARDs.MethodsSELECT-AXIS 2 (NCT04169373) was conducted under a master protocol and includes two separate studies (one for AS bDMARD-IR and one for non-radiographic axial spondyloarthritis [nr-axSpA]). The AS bDMARD-IR study is a randomized, double-blind, placebo (PBO)-controlled, phase 3 trial that enrolled adults ≥18 years with AS who met modified New York criteria, had BASDAI and pt’s assessment of total back pain scores ≥4 (numeric rating scale 0–10) at study entry, and had an IR to one or two bDMARDs (TNF inhibitor or IL-17 inhibitor). Pts were randomized 1:1 to receive oral UPA 15 mg once daily (QD) or PBO during the 14-week (wk) double-blind treatment period. The primary endpoint was ASAS40 response at wk 14. Multiplicity-controlled secondary endpoints evaluated at wk 14 were improvements from baseline in disease activity (ASDAS [CRP], ASDAS ID [&lt;1.3], ASDAS LDA [&lt;2.1], BASDAI50, ASAS20, and ASAS PR), pain (total and nocturnal back pain), function (BASFI), objective measure of inflammation (SPARCC MRI score of the spine), spinal mobility (BASMI), enthesitis (MASES), and quality of life (ASQoL and ASAS HI). Non-responder imputation incorporating multiple imputation (NRI-MI) was used to handle intercurrent events and missing data for binary endpoints. Cochran-Mantel-Haenszel (CMH) test and mixed-effect model for repeated measures (MMRM) were used for analyzing binary and continuous endpoints, respectively. Treatment-emergent adverse events (TEAEs) assessed through wk 14 are reported for pts who had ≥1 dose of study drug.ResultsAll 420 randomized pts with active AS received assigned treatment (UPA 15 mg, n=211; PBO, n=209); 409 (97%) received study drug through wk 14. Baseline demographic and disease characteristics were generally similar between treatment groups and reflective of an active AS bDMARD-IR population (74% male; mean age 42.4 years; mean disease duration 7.7 years; 83% HLA-B27 positive; mean BASDAI 6.8). Significantly more pts achieved the primary endpoint of ASAS40 response at wk 14 with UPA vs PBO (45% vs 18%; P&lt;0.0001; Figure 1); UPA showed onset of effect in ASAS40 as early as wk 4 (nominal P≤0.05). All multiplicity-controlled secondary endpoints met statistical significance for UPA vs PBO at wk 14 across multiple clinical domains of AS (P&lt;0.0001; Figure 1). The rate of TEAEs was similar between treatment groups through wk 14 (UPA, 41%; PBO, 37%). TEAEs led to discontinuation in 3 (1.4%) pts treated with PBO and none with UPA. Serious infections occurred with UPA (2.4%) but not with PBO and included 4 events of COVID-19 and 1 event of uveitis. Additional events of uveitis were reported in 3 (1.4%) pts treated with PBO. Inflammatory bowel disease (IBD) occurred in 1 (0.5%) pt on UPA and none on PBO. No malignancy, major adverse cardiovascular events, venous thromboembolic events, or death were reported with UPA; 1 event of malignancy was observed with PBO.ConclusionUPA 15 mg QD was significantly more effective than PBO over 14 wks of treatment in pts with active AS and IR to bDMARDs. No new safety risks were identified with UPA compared with its known safety profile.3,4 These findings are consistent with and complementary to those of SELECT-AXIS 1 (bDMARD-naïve AS population),1,2 and support the use of UPA in pts with active AS, including those who had a previous IR to bDMARD therapy.

OP0019 BIMEKIZUMAB IN PATIENTS WITH ACTIVE ANKYLOSING SPONDYLITIS: 24-WEEK EFFICACY &amp; SAFETY FROM BE MOBILE 2, A PHASE 3, MULTICENTRE, RANDOMISED, PLACEBO-CONTROLLED STUDY

OP0019 BIMEKIZUMAB IN PATIENTS WITH ACTIVE ANKYLOSING SPONDYLITIS: 24-WEEK EFFICACY &amp; SAFETY FROM BE MOBILE 2, A PHASE 3, MULTICENTRE, RANDOMISED, PLACEBO-CONTROLLED STUDY

P254 Secukinumab retention and safety in patients with active psoriatic arthritis or ankylosing spondylitis: two-year interim results of the observational SERENA study

Abstract Background/Aims SERENA is an ongoing, prospective, non-interventional study evaluating retention, effectiveness, safety/tolerability and quality of life in &amp;gt; 2,900 patients with moderate to severe plaque psoriasis, active psoriatic arthritis (PsA) or active ankylosing spondylitis (AS) treated with secukinumab at 438 sites across Europe for up to 5 years. We present interim results reporting secukinumab treatment retention and safety data through two years in PsA and AS patients. Methods This interim analysis presents data from 534 PsA and 470 AS patients enrolled (target population fulfilling eligibility criteria) and followed for at least two years. Patients (≥18 years) with active PsA or AS should have received at least 16 weeks secukinumab treatment before enrolment in the study. Retention rate was defined as percentage of patients who did not discontinue secukinumab treatment. Treatment break was defined as interruption of therapy for at least three months after last injection. Results The mean treatment duration prior to enrolment in the study was 1.0 year and 0.91 year for PsA and AS, respectively. The retention rates for secukinumab after one year since enrolment and since initiation of treatment were: PsA, 85.2% (n = 519, CI: 82.01-88.32) and 96.8% (n = 528, CI: 95.18-98.38); AS, 85.8% (n = 452, CI: 82.52-89.17) and 94.2% (n = 464, CI: 91.94-96.42), respectively. After two years since enrolment and since initiation of treatment, the retention rates were: PsA, 74.9% (n = 498, CI: 70.99-78.81) and 87.0% (n = 515, CI: 83.99-89.99); AS, 78.9% (n = 437, CI: 75.01-82.88) and 84.8% (n = 454, CI: 81.39-88.21), respectively. At baseline, the majority of PsA (79.5%; n/N=423/532) patients were receiving secukinumab 300 mg, while 97.0% (n/N=456/470) of AS patients were receiving secukinumab 150 mg. The majority of patients continued their initial secukinumab dose; “no dose change” in secukinumab treatment was reported after one and two years in the study (year one: PsA, 93.4% [n = 499] and AS, 92.6% [n = 435]; year two: PsA, 89.7% [n = 479] and AS, 87.9% [n = 413]). Secukinumab treatment break was recorded for 31 PsA patients (median [min, max] treatment break duration in days: 125.0 [61-461]) and for 42 AS patients (118.0 [61-813]), mainly due to adverse events reported in 58.1% (n = 18) and 45.2% (n = 19) of patients, respectively. The retreatment started with monthly dosing in most of the cases: PsA, 80.6% (n/N=25/31) and AS, 76.2% (n/N=32/42). No new or unexpected safety signals were reported. Conclusion Secukinumab retention rates in a real-world setting after more than two years since initiation of treatment and after two years since study enrolment indicate high persistence rates. Safety data collected prospectively for up to two years confirm the favorable safety profile of secukinumab. Disclosure K. Gaffney: Consultancies; AbbVie, Celgene, Lilly, Pfizer, Gilead, MSD, Novartis, UCB. Member of speakers’ bureau; AbbVie, Celgene, Lilly, Gilead, MSD, Novartis, UCB, Pfizer. Grants/research support; AbbVie, Celgene, Lilly, Pfizer, Gilead, MSD, Novartis, UCB. U. Kiltz: Consultancies; AbbVie, Biocad, Biogen, Chugai, Eli Lilly, Grünenthal, Hexal, Janssen, MSD, Novartis, Pfizer, Roche, UCB. Grants/research support; AbbVie, Biocad, Biogen, Chugai, Eli Lilly, Grünenthal, Hexal, Janssen, MSD, Novartis, Pfizer, Roche, UCB. P. Sfikakis: Consultancies; AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli-Lilly, Janssen, Novartis, Pfizer. Grants/research support; AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli-Lilly, Janssen, Novartis, Pfizer. N. Gullick: Consultancies; AbbVie, Celgene, Eli Lilly, Izana, Janssen, Novartis, UCB. Member of speakers’ bureau; AbbVie, Celgene, Eli Lilly, Izana, Janssen, Novartis, UCB. Grants/research support; AbbVie, Celgene, Eli Lilly, Izana, Janssen, Novartis, UCB. A. Theodoridou: Consultancies; UCB, Amgen, Novartis. J. Brandt-Juergens: Consultancies; AbbVie, Pfizer, Roche, Sanofi-Aventis, Novartis, Lilly, MSD, UCB, BMS, Janssen, Medac. Member of speakers’ bureau; AbbVie, Pfizer, Roche, Sanofi-Aventis, Novartis, Lilly, MSD, UCB, BMS, Janssen, Medac. E. Lespessailles: Consultancies; Amgen, Expanscience, Lilly, MSD. Member of speakers’ bureau; Amgen, Expanscience, Lilly, MSD. Grants/research support; Abbvie, Amgen, Lilly, MSD, UCB,. J. Fang: Other; Employee of Novartis. E. Pournara: Shareholder/stock ownership; Novartis. Other; Employee of Novartis. B. Schulz: Other; Employee of Novartis. P. Jagiello: Other; Employee of Novartis.

Effectiveness of a supervised group exercise therapy based on the biopsychosocial model introduced simultaneously with anti-TNF therapy in anti-TNF-naive patients with active ankylosing spondylitis.

This study aimed to investigate the effectiveness of a supervised group exercise therapy based on the biopsychosocial model introduced simultaneously with antitumor necrosis factor (TNF) therapy in anti-TNF-naive patients with active ankylosing spondylitis (AS). Forty-eight patients were divided into two groups: the control group (CG; n = 36) received only anti-TNF therapy, and the study group (SG; n = 12) received the supervised exercise therapy based on the biopsychosocial model in addition to anti-TNF therapy. The measurements of disease activity and functionality were evaluated by The Bath AS Disease Activity Index (BASDAI) and The Bath AS Functional Index (BASFI) respectively. Other outcome measures evaluated biopsychosocial status, emotional state, spinal mobility, pain, fatigue, sleep, and quality of life. All measurements were applied to both groups at baseline and repeated 12 weeks later. BASDAI and BASFI analyses revealed significant differences between groups in favor of the SG (p < 0.05). At the end of the 12 weeks, the results showed that there were additional improvements in all outcome measurement parameters in the SG compared to the CG. The supervised group exercise therapy based on the biopsychosocial model introduced simultaneously with anti-TNF therapy is more effective than only anti-TNF therapy in anti-TNF-naive patients with active AS.

Evaluation of adalimumab biosimilar candidate (HS016) in Chinese patients with active ankylosing spondylitis based on a health survey: sub-analysis of a phase 3 study

ObjectiveThe equivalence of the biosimilar HS016 to adalimumab (Humira) for the treatment of active ankylosing spondylitis (AS) patients has been previously validated. The aim was to compare the efficacy of HS016 and adalimumab in stratified subgroups at different time points using Health Assessment Questionnaire for Spondyloarthropathies (HAQ-S) and short form 36 (SF-36) questionnaires.MethodsWe carried out a multicenter, randomized, double-blind, parallel, positive control, phase 3 trial of patients with active AS. They were selected randomly to be subcutaneously administered 40 mg HS016 or adalimumab every 2 weeks for a total treatment period of 24 weeks in a 2:1 ratio. A health surveys were used to assess mental and physical improvements of patients as well as other factors.ResultsHAQ-S revealed that changes in scores from baseline in both groups were time dependent until 14 weeks and that during the first 4 weeks of treatment the changes declined rapidly. The SF-36 health survey revealed that both HS016 and adalimumab produced rapid beneficial effects against AS during the first 2 weeks of therapy, which gradually declined between 2 and 12 weeks and flattened out after 12 weeks until 24 weeks.ConclusionThis trial demonstrated that both HS016 and adalimumab produced rapid improvements in symptoms during the first 2 weeks of treatment. These findings suggest that HS016 is an alternative economical treatment for Chinese AS patients producing a rapid amelioration of symptoms, aiding them to recover their lifestyle satisfaction.Trial registrationhttp://www.chictr.org.cn/enindex.aspx, ChiCTR1900022520, retrospectively registered.Key points• HS016 and adalimumab produced rapid AS symptom improvements during the first 2 weeks followed by a slowdown of improvements until week 4 with afterwards few improvements evaluated by HAQ-S• The improvements according to the short form of the 36 (SF-36) questionnaires revealed similar trends as for HAQ-S• There was no significant difference in HAQ-S and SF-36 scores between HS016 and adalimumab

Comparative efficacy and safety of secukinumab 75 mg, 150 mg, and 300 mg inpatients with active ankylosing spondylitis.

The purpose of this research was to assess the efficacy and safety of secukinumab at various doses in patients with active ankylosing spondylitis (AS). A Bayesian network meta-analysis was performed using direct and indirect data from randomized controlled trials (RCTs) investigating the efficacy and safety of secukinumab 75, 150, and 300 mg in patients with active AS. Data of 1,049 patients from three RCTs were examined. In AS patients with inadequate response (IR) to tumor necrosis factor inhibitor (TNFI), secukinumab 300mg was associated with the most favorable assessment of Spondyloarthritis International Society 40% (ASAS40) response rate according to surface under the cumulative ranking curve (SUCRA), while placebo was associated with the least favorable outcomes. In TNFI-IR patients with AS, ASAS40 was significantly higher in the secukinumab 300, 150, and 75 mg groups than in the placebo group. SUCRA-based rating of likelihood indicated that secukinumab 300 mg was most likely to be the best therapy to achieve ASAS40 response rate, followed by secukinumab 150 mg and 75 mg and placebo. ASAS20 response rate showed a distribution pattern identical to ASAS40 response rate. In TNFI-naïve patients with AS, the response rates for ASAS40 and ASAS20 were also significantly higher in the 300, 150, and 75 mg groups than in the placebo group. There was no substantial difference in the number of severe adverse effects (SAEs) between the treatment groups. Secukinumab demonstrated dose-dependent efficacy in TNFI-IR patients with AS without increasing the risk of SAEs.

OP0141 EFFECTS OF FILGOTINIB ON SPINAL LESIONS IN ANKYLOSING SPONDYLITIS: MAGNETIC RESONANCE IMAGING DATA FROM THE TORTUGA TRIAL

Background:The oral Janus kinase 1 preferential inhibitor filgotinib (FIL) significantly improved Spondyloarthritis Research Consortium of Canada (SPARCC) magnetic resonance imaging (MRI) inflammation scores (bone marrow oedema) in the spine and sacroiliac joints vs placebo (PBO) in the Phase 2 TORTUGA trial (NCT03117270) in patients with active ankylosing spondylitis (AS).1Objectives:This post-hoc analysis evaluated the effects of FIL on Canada-Denmark (CANDEN) MRI measures of spinal inflammation and structural lesions in patients from the TORTUGA trial.Methods:TORTUGA was a PBO-controlled, multicentre, double-blind, randomised trial. Patients with active AS (as per modified New York classification criteria, with sacroiliitis confirmed by central reading) were treated with FIL 200 mg (n=58) or PBO (n=58) once daily for 12 weeks. MRI of the total spine was conducted at baseline and at treatment end. Scans were re-evaluated post-hoc by 2 independent experts (blinded to time point and assigned treatment) using the CANDEN method;2 inter-reader discrepancies were resolved by an independent adjudicator. Observed changes from baseline were evaluated using analysis of covariance, with factors for treatment, baseline value, and randomisation stratification by prior tumour necrosis factor inhibitor use. Least-squares (LS) mean changes from baseline and between-group differences with 95% confidence intervals (CI) were calculated; P values are nominal.Results:MRI scans from 88 patients (47 FIL, 41 PBO) with an evaluable scan at baseline and Week 12 (or early termination) were re-evaluated. Baseline characteristics were generally similar between patients with/without an MRI scan. Of those with MRI scans, mean total spine inflammation score (which ranges from 0–614) was higher, and mean ankylosis score (which ranges from 0–460) was lower, in the FIL vs PBO group at baseline. Total spine inflammation scores decreased from baseline with FIL but not with PBO (Figure and Table; P=0.0003 for between-group difference). Cumulative probability plots favoured FIL over PBO for change from baseline in subregion inflammation scores, including posterolateral elements (i.e. sum of lesions in ribs, transverse processes, spinous processes, soft tissue inflammation, and postero-lateral vertebral body), facet joint, and vertebral body. Total spine fat lesion scores numerically increased from baseline in the FIL but not PBO group (P=0.0878 for between-group difference; Table). There were no significant differences between groups for changes in erosion (P=0.1956) or ankylosis (P=0.3888) scores (Table).Table 1.Change from baseline at Week 12 in CANDEN total spine inflammation, total spine fat, total spine bone erosion, and ankylosis scoresTreatment groupnSample mean (SE)LS mean (SE)95% CI of treatment meanLS mean of group difference (SE)95% CI of group differenceBetween-group P valueTotal spine inflammation scoreFilgotinib47–4.98 (0.96)–4.40 (1.13)–6.65, –2.15–4.49 (1.21)–6.85, –2.120.0003Placebo410.29 (0.78)0.09 (1.13)–2.17, 2.34Total spine fat scoreFilgotinib471.01 (0.62)1.09 (0.66)–0.22, 2.401.18 (0.69)–0.18, 2.550.0878Placebo41–0.25 (0.19)–0.09 (0.66)–1.40, 1.21Total spine bone erosion scoreFilgotinib470.01 (0.02)0.07 (0.03)0.00, 0.140.05 (0.04)–0.02, 0.120.1956Placebo41–0.02 (0.03)0.02 (0.03)–0.04, 0.09Total ankylosis scoreFilgotinib470.30 (0.29)0.23 (0.31)–0.40, 0.850.28 (0.34)–0.37, 0.940.3888Placebo41–0.01 (0.08)–0.06 (0.31)–0.68, 0.56SE, standard errorConclusion:This is the first PBO-controlled trial to demonstrate a decrease in inflammatory activity with FIL, not only in the spinal vertebrae but also in the postero-lateral elements of the spine and facet joints. As expected in a 12-week study period, no changes in erosion or ankylosis were seen, while fat lesions showed a tendency to increase with FIL. Larger trials are needed to confirm these results.

POS0234 SECUKINUMAB RETENTION AND SAFETY IN PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS OR ANKYLOSING SPONDYLITIS: 2 YEAR INTERIM RESULTS OF THE OBSERVATIONAL SERENA STUDY

Background:SERENA is an ongoing, prospective, non-interventional study evaluating retention, effectiveness, safety/tolerability and quality of life in more than 2900 patients (pts) with moderate to severe plaque psoriasis, active psoriatic arthritis (PsA) or active ankylosing spondylitis (AS) treated with secukinumab (SEC) at 438 sites across Europe for a period of up to 5 years1.Objectives:We present interim results reporting SEC treatment retention and safety data through 2 years in the PsA and AS pts enrolled in the study.Methods:This interim analysis presents data from 534 PsA and 470 AS pts who were enrolled (target population fulfilling all eligibility criteria) in the study and were followed up for at least 2 years. Pts (aged ≥18 years) with active PsA or AS should have received at least 16 weeks SEC treatment before enrolment in the study1. Retention rate was defined as the percentage of pts who have not discontinued SEC treatment. A treatment break was defined as interruption of therapy for at least 3 months after last injection.Results:The mean treatment duration prior to enrolment in the study was 1.0 year and 0.91 year for PsA and AS, respectively. The retention rates for SEC after 1 year since enrolment and since initiation of treatment were: PsA, 85.2% [n=519, CI: 82.01–88.32] and 96.8% [n=528, CI: 95.18–98.38]; AS, 85.8% [n=452, CI: 82.52–89.17] and 94.2% [n=464, CI: 91.94–96.42], respectively. After 2 years since enrolment and since initiation of treatment, the retention rates were: PsA, 74.9% [n=498, CI: 70.99–78.81] and 87.0% [n=515, CI: 83.99–89.99]; AS, 78.9% [n=437, CI: 75.01–82.88] and 84.8% [n=454, CI: 81.39–88.21], respectively. Survival probabilities for individual indications are presented in Figure 1. At baseline, the majority of PsA (79.5%; n/N=423/532) pts were receiving SEC 300 mg, while 97.0% (n/N=456/470) of AS pts were receiving SEC 150 mg. The majority of pts continued their initial SEC dose; “no dose change” in SEC treatment was reported after 1 and 2 years in the study (Year 1: PsA, 93.4% [n=499] and AS, 92.6% [n=435]; Year 2: PsA, 89.7% [n=479] and AS, 87.9% [n=413]). SEC treatment break was recorded for 31 PsA pts [median (min, max) treatment break duration in days: 125.0 (61, 461)] and for 42 AS [118.0 (61, 813)] pts mainly due to adverse events reported in 58.1% (n=18) and 45.2% (n=19) of pts, respectively. The retreatment started with monthly dosing in most of the cases: PsA, 80.6% (n/N=25/31) and AS, 76.2% (n/N=32/42). No new or unexpected safety signals were reported (Table 1).Table 1.Safety profile of treatment-emergent adverse events within the study periodAE summary, n (%)PsA N=575AS N=499Year 1Year 2Year 1Year 2Subject with any AE239 (41.6)289 (50.3)203 (40.7)247 (49.5)Subject with any serious AE29 (5.0)45 (7.8)29 (5.8)44 (8.8)Subject with AE leading to discontinuation55 (9.6)84 (14.6)47 (9.4)62 (12.4)Death0 (0.0)0 (0.0)0 (0.0)1 (0.2)AEs of special interest, n (IR per 100 subject-years)Serious infections and infestations5 (0.96)9 (0.95)8 (1.78)11 (1.33)Candida infections1 (0.19)2 (0.21)2 (0.44)2 (0.24)Malignancy5 (0.96)7 (0.74)N/R3 (0.36)Major adverse cardiovascular eventsN/R1 (0.11)2 (0.44)3 (0.36)Inflammatory bowel diseaseN/RN/R1 (0.22)1 (0.12)N, total number of patients in the safety set; n, number of patients with event; AE, adverse events; IR, incidence rate; N/R, not reported.Conclusion:Secukinumab retention rates in a real world setting after more than 2 years since initiation of treatment and after 2 years since enrolment in the study indicate high persistence rates. Safety data collected prospectively for up to 2 years confirm the favorable safety profile of secukinumab.

Tofacitinib for the treatment of ankylosing spondylitis: a phase III, randomised, double-blind, placebo-controlled study

ObjectiveTo assess the efficacy/safety of tofacitinib in adult patients with active ankylosing spondylitis (AS).MethodsThis phase III, randomised, double-blind, placebo-controlled study enrolled patients aged ≥18 years diagnosed with active AS, meeting...

P186 Secukinumab effectiveness and safety in patients with active psoriatic arthritis or ankylosing spondylitis: interim analysis of an observational study in the real-world setting

Abstract Background/Aims SERENA is an ongoing, non-interventional study involving ∼400 European sites with an observation period of ≤ 5 years to evaluate retention, effectiveness, safety/tolerability and quality of life with secukinumab (SEC) in patients with moderate-to-severe plaque psoriasis, active psoriatic arthritis (PsA) or active ankylosing spondylitis (AS) in the real world. We present effectiveness and safety data through 1 year in the 577 PsA and 507 AS patients enrolled, of which 533 PsA and 461 AS patients comprised the target study population (fulfilling all eligibility criteria). Methods Patients (aged ≥18 years) with active PsA or AS who were treated for at least 16 weeks with SEC were enrolled. Effectiveness assessments included 78 tender joint count/76 swollen joint count, PGA, total pain (VAS, 0-100 mm), presence of enthesitis/dactylitis and PASI75/90/100 in patients with PsA, and BASDAI, PtGA, C-reactive protein, ASDAS and total spinal pain in patients with AS. Results Mean disease duration from diagnosis to enrolment was 8.6 and 9.8 years for PsA and AS patients. Patients received SEC for a mean duration of 1 year prior to enrolment (range: 0.90-1.00). In total, 64.7% (N = 533) of PsA and 60.7% (N = 461) of AS patients received other biologic drugs prior to SEC treatment, with 59.7% and 52.7% of PsA and AS patients receiving at least two different biologic drugs. Most patients pre-treated with biologics discontinued biologic treatment due to lack of efficacy (88.0% PsA; 86.8% AS). Retention rates for SEC after 1 year were 85.9% and 86.5% in PsA and AS patients. Responses across all effectiveness assessments in both cohorts were maintained or improved after 1 year of observation (Table 1). No new or unexpected safety signals were reported. P186 Table 1:Effectiveness outcomes in patients with PsA or AS at enrolment and Year 1Characteristic, mean±SD (M), unless otherwise specifiedPsA (N = 533)PsA (N = 533)AS (N = 461)AS (N = 461)EnrolmentYear 1EnrolmentYear 1Total pain (VAS 0-100 mm)31.80±24.28a (432)30.77±24.57a (322)34.68±24.23b (350)34.16±24.49b (228)Presence of tender or swollen joint, n/M (%)280/520 (53.8%)158/373 (42.4%)--Tender joint count, mean [min-max] (m)6.5 [0-68] (203)6.8 [0-78] (140)--Swollen joint count, mean [min-max] (m)3.3 [0-38] (203)2.8 [0-23] (140)--Presence of dactylitis, n/M (%)33/516 (6.4%)13/370 (3.5%)--Enthesitis index0.4±1.0c (276)c0.3±0.9c (243)c0.7±1.70d (246)0.6±1.7d (170)HAQ-DI0.83±0.70 (398)0.83±0.72 (268)--BASDAI--3.20±2.28 (436)3.24±2.36 (270)ASDAS-CRP--2.25±0.94 (229)2.27±0.97 (173)hsCRP, mg/L--8.53±13.42 (285)8.10±14.72 (218)PtGA (NRS) (VAS 0-10 cm)--4.18±2.32 (366)4.07±2.37 (246)aTotal pain;bTotal back pain;cLeeds enthesitis index;dMaastricht Ankylosing Spondylitis Enthesitis Score. AS, ankylosing spondylitis; ASDAS-CRP, Ankylosing Spondylitis Disease Activity Score-C-reactive protein; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; HAQ-DI, Health Assessment Questionnaire Disability Index; hsCRP, high sensitivity C-reactive protein; m, number of patients with detailed assessments of tender or swollen joints; M, number of patients with evaluation; n, number of patients with a positive response; N, number of patients in the study population; NRS, numeric rating scale; PsA, psoriatic arthritis; PtGA, Patient’s Global Assessment; SD, standard deviation; VAS, visual analogue scale. Conclusion Patients in SERENA had long-standing disease with more than half previously treated with biologics, most of whom had discontinued treatment due to lack of efficacy. SEC showed sustained effectiveness, a high retention rate and favourable safety profile in PsA and AS patients in the real world over 1 year of observation. Incomplete data due to lack of rigorous monitoring (an intrinsic weakness of observational studies) must be considered when interpreting real-world findings. Disclosure K. Gaffney: Grants/research support; Research grants, consultancy fees and/or speaker fees from AbbVie, Celgene, Lilly, Pfizer, Gilead, MSD, Novartis and UCB. N. Gullick: Grants/research support; Research support, consultancy fees and/or speakers fees from AbbVie, Celgene, Eli Lilly, Izana, Janssen, Novartis, UCB. U. Kiltz: Grants/research support; Research grants, support and/or consultancy fees from AbbVie, Biocad, Biogen, Chugai, Eli Lilly, Grünenthal, Janssen, MSD, Novartis, Pfizer, Roche and UCB. P. Sfikakis: Grants/research support; Research grants, support and consultancy fees from AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, Novartis and Pfizer. A. Theodoridou: Honoraria; Consultancy fees from UCB, Amgen, Novartis. J. Brandt-Jürgens: Honoraria; Consultancy fees and speaker honoraria from AbbVie, Pfizer, Roche, Sanofi-Aventis, Novartis, Lilly, MSD, UCB, BMS, Janssen and Medac. E. Lespessailles: Honoraria; Received speaker and consultant fees from Amgen, Expanscience, Lilly and MSD, and research grants from AbbVie, Amgen, Lilly, MSD and UCB. C. Perella: Other; Novartis employee. E. Pournara: Shareholder/stock ownership; Novartis shareholder. Other; Novartis employee. B. Schulz: Other; Novartis employee. J. Veit: Other; Novartis employee.

Safety and Efficacy of Prefilled Liquid Etanercept-Biosimilar Yisaipu for Active Ankylosing Spondylitis: A Multi-Center Phase III Trial.

IntroductionThe aim of this work is to examine the efficacy and safety of prefilled liquid etanercept-biosimilar Yisaipu versus lyophilized Yisaipu in active ankylosing spondylitis (AS) patients.MethodsThis double-blind, phase III trial with non-inferiority design randomized adult patients with active AS in a 3:1:1 ratio to receive twice-weekly 25-mg prefilled liquid Yisaipu for a total of 48 injections (group I, n = 330), once-weekly 50-mg prefilled liquid Yisaipu for 24 injections (group II, n = 110), or twice-weekly 25-mg lyophilized Yisaipu for 48 injections (group III, n = 110). Both physicians and patients who received 25-mg twice-weekly lyophilized or liquid Yisaipu were blinded to treatment assignment while patients who received 50-mg once-weekly liquid Yisaipu received treatment in an open-label design. In addition, 90 patients in the PK/PD study were randomized in a 1:1:1 ratio to each group. The primary outcome was the proportion of patients who achieved ASAS20 at week 24.ResultsA total of 640 subjects were enrolled. The proportion of patients who attained ASAS20 at week 24 was 85.56% in group I, 85.71% in group II, and 83.45% in group III (group I vs. III, P = 0.545; group II vs. III, P = 0.605). The difference between group I and III was 2.10% (95% CI − 5.06%, 9.27%) and 2.26% (95% CI − 6.21%, 10.73%) between group II and III, meeting the non-inferiority threshold (Δ = − 15%) (P < 0.001). Except for a statistical difference between group I (75.83%) and group III at week 8 (64.75%, P = 0.011), there was no statistical difference in the ASAS20 attainment rate among the three groups at other time points. The incidence of serious adverse events was comparable among the three groups (group I, 2.50%, II, 2.86% and III, 1.43%; P > 0.05). No deaths were reported.ConclusionsOnce-weekly 50-mg or twice-weekly 25-mg prefilled liquid Yisaipu is safe and non-inferior to twice-weekly 25-mg lyophilized Yisaipu.Trial RegistrationCTR20130124 and NCT04345458.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-021-00276-1.

Cost of Illness, Quality of Life, and Work Outcomes in Active Ankylosing Spondylitis Patients Treated With Adalimumab in China.

Objectives: To access the cost of illness, quality of life and work limitation in active ankylosing spondylitis (AS) patients using adalimumab in China.Methods: A prospective study was performed in 91 patients with active AS in China. Adult patients (aged ≥ 18 years) fulfilled the 1984 New York modified criteria of AS with the Bath Ankylosing Spondylitis Disease Activity Index ≥ 4 were enrolled. All participants received adalimumab (40 mg per 2 weeks) therapy and completed questionnaires about disease characteristics, quality of life and cost. Only patients with pay-work completed the Work Limitation Questionnaire and Work productivity and activity impairment questionnaire in AS. Factors associated with work outcomes were evaluated.Results: A total of 91 patients with mean age of 30 years old (87.8% males) and mean disease duration of 10 years received adalimumab treatment for 24 weeks. The annual estimated cost of each patient was $37581.41 while the direct cost accounted for 84.6%. Seventy-eight percent of patients have a paid job with average work productivity loss of 0.28 measured by work limitation questionnaire, absenteeism and presenteeism were 10.22 and 43.86%, respectively, with a mean work productivity loss of 47.92% measured by Work productivity and activity impairment questionnaire in AS. Patients experienced significantly greater improvements after adalimumab treatment in presenteeism, absenteeism, work productivity, and quality of life.Conclusions: The cost of AS patients with adalimumab therapy was high in China. Disease activity, physical function, quality of life, and work outcomes improved significantly after therapy.

Propensity score matching/reweighting analysis comparing intravenous golimumab to infliximab for ankylosing spondylitis using data from the GO-ALIVE and ASSERT trials

ObjectiveTo compare the relative efficacy of intravenous golimumab (GOL IV) and infliximab (IFX) for active ankylosing spondylitis (AS).MethodsPropensity score (PS) methods were used to compare the efficacy of GOL IV 2 mg/kg and IFX 5 mg/kg using individual patient data (IPD) from the active arms of the phase 3 GO-ALIVE and ASSERT studies. Outcomes included the proportion of patients with a ≥ 20% improvement in the Assessment of Spondyloarthritis International Society Criteria (ASAS20), change from baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) score, and change from baseline in C-reactive protein (CRP) levels from weeks 4–52.ResultsBefore matching, 105 patients were treated with GOL IV and 201 patients were treated with IFX. After matching on all covariates, 118 patients were included in the ASAS20 analysis, 96 in the BASFI analysis, and 160 in the CRP analysis. After matching, GOL IV showed significantly greater improvement in ASAS20 response than IFX for weeks 28–44 (e.g., OR = 9.05 [95% CI 1.62–50.4] at week 44) and was comparable in change from baseline in BASFI scores and CRP levels to IFX at all time points. Results were robust for inclusion of different sets of covariates in scenario analyses.ConclusionsThis is the first analysis of its kind to leverage clinical trial data to compare two biologics using PS methods in the treatment of active AS. Overall, GOL IV was associated with greater improvement in ASAS20 response than IFX in patients with AS at 28, 36, and 44 weeks of follow-up.Key Points• Although intravenous golimumab (GOL IV) and infliximab (IFX) are the only two IV-based tumor necrosis factor (TNF) inhibitors with demonstrated phase 3 clinical efficacy in patients with ankylosing spondylitis (AS), no study has evaluated their comparative efficacy in a head-to-head trial.• Propensity score matching was used to derive indirect treatment comparisons of GOL IV and IFX for ≥ 20% in the Assessment of Spondyloarthritis International Society Criteria (ASAS20), change in Bath Ankylosing Spondylitis Functional Index (BASFI), and change in C-reactive protein (CRP) using individual patient data from the GO-ALIVE and ASSERT phase 3 trials.• Propensity score matched indirect comparisons showed improved relative efficacy of GOL IV compared to IFX; after matching for up to 16 baseline covariates, GOL IV was associated with significantly greater odds of ASAS20 response at weeks 28, 36, and 44 than IFX as well as equivalent changes from baseline in BASFI and CRP.• This novel application of propensity score matching using data from phase 3 trials, the first analysis of its kind in AS, allowed adjustment for important imbalances in prognostic factors between trials to generate estimates of comparative efficacy between GOL IV and IFX in the absence of a head-to-head trial between these treatments.

Dual neutralisation of interleukin-17A and interleukin-17F with bimekizumab in patients with active ankylosing spondylitis: results from a 48-week phase IIb, randomised, double-blind, placebo-controlled, dose-ranging study

ObjectivesBimekizumab selectively neutralises both interleukin (IL)-17A and IL-17F. We report efficacy and safety in a phase IIb dose-ranging study in patients with active ankylosing spondylitis (AS).MethodsAdults with AS (fulfilling modified...

TNF Receptor: Fc Fusion Protein Downregulates RANKL/OPG Ratio by Inhibiting CXCL16/CXCR6 in Active Ankylosing Spondylitis.

Clinical studies indicate that recombinant tumor necrosis factor receptor:Fc fusion protein (rhTNFR:Fc) quickly alleviates symptoms and physical signs of active Ankylosing Spondylitis (AS), improving the manifestation of spinal inflammation on radiological imaging. However, the regulatory mechanism of rhTNFR:Fc in the chemokine pathway is unclear. Thus we study the mechanism of phlogogenic activity of CXCL16/CXCR6 in AS and the related mechanism of rhTNFR: Fc treatment. Thirty-two cases of active AS were treated with rhTNFR:Fc for 3 consecutive months. Clinical response was evaluated at baseline and after treatment. CXCL16/CXCR6 expression as well as Receptor Activator Of Nuclear Factor-Κb Ligand (RANKL)/Osteoprotegerin (OPG), essential molecules for osteoclast differentiation, were studied in AS before and after treatment. Further, the proliferation of lymphocytes and the RANKL level stimulated by recombinant human CXCL16 (rhCXCL16) were measured in vitro. Thirty cases responded to rhTNFR:Fc treatment. The RANKL level, RANKL/OPG ratio, CXCLl6 level in serum, and CXCLl6 and CXCR6 mRNA levels in active AS were higher than those in controls and treated patients (P<0.001). rhCXCL16 treatment increased lymphocyte proliferation and RANKL level in active AS (P<0.001), but not in controls or treated patients (P>0.05). A positive linear correlation was noted between CXCL16 serum levels and RANKL/OPG ratio and between CXCL16 levels and C-reactive protein results (P<0.001). Our findings suggest that rhTNFR:Fc suppresses inflammation and bone destruction of AS by reducing the RANKL/OPG ratio through inhibition of the CXCL16/CXCR6 pathway.

Efficacy and safety of a new original interleukin 17A inhibitor in the treatment of patients with active ankylosing spondylitis: results of a basic (BCD-085-3/AILAS) and extended (BCD-085-3ext/AILAS-II) phase II clinical trial

The paper presents the results of a double-blind (BCD-085-3/AILAS) phase II clinical trial of the original interleukin 17A (IL17A) inhibitor BCD-085 prescribed at different doses to patients with active ankylosing spondylitis (AS) and those of an extended (BCD-085-3ext/AILAS-II) trial characterizing the efficacy and safety of this drug when used for a year. The objective of the AILAS study is to determine the therapeutically effective and safe dose of BCD-085 in the treatment of active AS. The efficacy, safety, and immunogenicity of BCD-085 during its annual use were additionally evaluated in the extended trial. Subjects and methods . The investigation enrolled 89 patients diagnosed as having active (BASDAI scores >4.0; mean spinal pain scores >4.0) AS that met the 1984 New York classification criteria. After the end of the screening period, the patients were randomized at a ratio of 1:1:1:1 in one of four groups that received 40; 80 or 120 mg of BCD-085 subcutaneously or placebo on day 1 of weeks 0, 1, 2 and then once every two weeks up to week 12. The primary end point was the number of patients who achieved an ASAS20 response at week 16. The investigation evaluated the safety of the drug, by calculating the total incidence of adverse events (AEs) and serious AEs (SAEs) and the number of cases of premature therapy termination because of AEs. Results and discussion . An ASAS20 response at week 16 was achieved in 72.7% of patients receiving 40 mg of BCD-085, in 81.8% of those receiving 80 mg, in 90.9% of those receiving 120 mg, and in 42.9% of cases in the placebo group (p=0.004). The superiority of BCD-085 over placebo was proven for 80- and 120-mg doses. The fastest and most pronounced effect was observed in patients treated with 120 mg of BCD-085. In the extended study, an ASAS20 response at week 52 was recorded in 86.4% of patients. One or more AEs during the first 16 weeks of therapy were reported in 11 (50.0%) patients of the 40-mg group; in 6 (27.3%) of the 80 mg group; in 4 (18.2%) of the 120 mg group and in 7 (31.8%) of the placebo group (p=0.183). The frequency and spectrum of AEs did not significantly differ in patients who received placebo and BCD-085 in different doses. No SAE was recorded. Conclusion. Phase II study yielded data demonstrating the high efficacy and good tolerance of BCD-085 in the treatment of active AS. The best effect and optimal tolerance were demonstrated for a dose of 120 mg.

Efficacy and safety of loxoprofen hydrogel patch versus loxoprofen tablet in patients with ankylosing spondylitis: A 4-week randomized, open-label study.

The aim of the present study was to assess the efficacy and safety of loxoprofen sodium hydrogel patch (LX-P) vs. loxoprofen sodium tablet (LX-T) in patients with active ankylosing spondylitis (AS). The study population consisted of patients who met the modified New York radiographic criteria for AS and had active disease. Patients were randomly assigned to either the LX-P group (LX-P 100 mg per day) or LX-T group (LX-T 60 mg 3 times daily) for 4 weeks. The primary efficacy endpoint was the percentage of patients reaching Assessment in Ankylosing Spondylitis 20% (ASAS20) response at week 4. Secondary efficacy outcomes included ASAS5/6 response rate and changes from baseline to week 4 for Ankylosing Spondylitis Disease Activity Score, patient's global assessment of disease activity, and pain score. Of the 70 randomized patients included, 35 patients were allocated to the LX-P group and 35 to the LX-T group. No significant differences were observed between the LX-P and LX-T groups in the proportion of patients achieving ASAS20 response at week 4 (54.3 vs. 74.3%; P=0.081), nor in the ASAS5/6 response and changes of efficacy outcomes between the two groups. Furthermore, patients without peripheral arthritis in the LX-P group were more likely to achieve ASAS20 response. There was a decreased incidence of gastrointestinal adverse events in the LX-P group, but this was not significant. There was no significant differences in efficacy and safety between topical LX-P and oral LX-T administration for patients with active AS.