Biologic-naive Patients Research Articles

Effect of Therapy on Radiographic Progression in Axial Spondyloarthritis: A Systematic Review and Meta-Analysis.

To investigate the effect of therapies on radiographic progression in patients with axial spondyloarthritis (SpA). A comprehensive database search for studies assessing radiographic progression in axial SpA (particular treatment versus no treatment of interest) was performed. Study-specific standardized mean differences in treatment outcomes at 2 and ≥4 years were estimated and combined using random-effects models. Twenty-four studies in patients with axial SpA were identified, of which 18 involved tumor necrosis factor inhibitors (TNFi), 8 involved nonsteroidal antiinflammatory drugs (NSAIDs), and 1 involved secukinumab. Spinal radiographic progression, as measured by the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS), was not significantly different between TNFi-treated and biologics-naive patients at 2 years (mSASSS difference -0.73 [95% confidence interval (95% CI) -1.52, 0.12], I2 = 28%) and ≥4 years (mSASSS difference -2.03 [95% CI -4.63, 0.72], I2 = 63%). Sensitivity analyses restricted to studies with a low risk of bias showed a significant difference in spinal radiographic progression between TNFi-treated and biologics-naive patients at ≥4 years (mSASSS difference -2.17 [95% CI -4.19, -0.15]). No significant difference in spinal radiographic progression was observed between NSAID-treated and control patients (mSASSS difference -0.30 [95% CI -2.62, 1.31], I2 = 71%) or between secukinumab-treated and biologics-naive patients (mSASSS difference -0.34 [95% CI -0.85, 0.17]). With regard to treatment differences in patients with nonradiographic axial SpA or in patients with radiographic progression measured using the sacroiliac joint score, an insufficient number of studies were available for analysis. Although no significant protective effect of TNFi treatment on spinal radiographic progression was seen over the course of 2 years or ≥4 years in patients with axial SpA, our analysis restricted to studies with a low risk of bias showed a protective effect of TNFi after ≥4 years. Therefore, long-term TNFi exposure might confer beneficial effects on spinal radiographic progression in axial SpA. No difference in radiographic progression at 2 years was seen in either the NSAID or secukinumab treatment groups compared to their controls. Future studies should explore the effects of biologic treatment on radiographic progression, as well as the effects of long-term biologics exposure, in patients with early axial SpA or those with nonradiographic axial SpA.

Guselkumab in biologic-naive patients with active psoriatic arthritis (DISCOVER-2): a double-blind, randomised, placebo-controlled phase 3 trial

The interleukin-23 (IL-23)/T-helper 17 cell pathway is implicated in psoriatic arthritis pathogenesis. Guselkumab, an IL-23 inhibitor that specifically binds the IL-23 p19 subunit, significantly and safely improved psoriatic arthritis in a phase 2 study. DISCOVER-2 was a phase 3 trial to assess guselkumab in biologic-naive patients with psoriatic arthritis. This phase 3, double-blind, placebo-controlled study was done at 118 sites in 13 countries across Asia, Europe, and North America. We enrolled biologic-naive patients with active psoriatic arthritis (at least five swollen joints, at least five tender joints, and C-reactive protein ≥0·6 mg/dL) despite standard therapies. Patients were randomly assigned (1:1:1, computer-generated permuted blocks; stratified by baseline disease-modifying antirheumatic drug use and C-reactive protein concentration) to subcutaneous injections of guselkumab 100 mg every 4 weeks; guselkumab 100 mg at weeks 0, 4, then every 8 weeks; or placebo. The primary endpoint was American College of Rheumatology 20% improvement (ACR20) response at week 24 in all patients per assigned treatment group. Safety was assessed in all patients per treatment received. This trial is registered at ClinicalTrials.gov, NCT03158285 (active, not recruiting). From July 13, 2017, to Aug 3, 2018, 1153 patients were screened, of whom 741 were randomly assigned to receive guselkumab every 4 weeks (n=246), every 8 weeks (n=248), or placebo (n=247). One patient in the every 4 weeks group and one in the placebo group did not start treatment, and the remaining 739 patients started treatment; 716 patients continued treatment up to week 24. Significantly greater proportions of patients in the guselkumab every 4 weeks group (156 [64%] of 245 [95% CI 57-70]) and every 8 weeks group (159 [64%] of 248 [58-70]) than in the placebo group (81 [33%] of 246 [27-39]) achieved an ACR20 response at week 24 (percentage differences vs placebo 31% [95% CI 22-39] for the every 4 weeks group and 31% [23-40] for the every 8 weeks group; both p<0·0001). Up to week 24, serious adverse events occurred in eight (3%) of 245 patients receiving guselkumab every 4 weeks (three serious infections), three (1%) of 248 receiving guselkumab every 8 weeks (one serious infection), and seven (3%) of 246 receiving placebo (one serious infection). No deaths occurred. Guselkumab, a human monoclonal antibody that specifically inhibits IL-23 by binding the cytokine's p19 subunit, was efficacious and demonstrated an acceptable benefit-risk profile in patients with active psoriatic arthritis who were naive to treatment with biologics. These data support the use of selective inhibition of IL-23 to treat psoriatic arthritis. Janssen Research and Development.

Dosage Adjustments in Patients With Psoriasis on Etanercept: A Retrospective Chart Review

Etanercept, 1 of 11 Food and Drug Administration (FDA)–approved biologics used for the treatment for psoriasis, may often be used at off-label dosages. The aim of this retrospective chart review was to determine the frequency of off-label dosing in a single center and the reasons for these deviations as well as the outcomes. The results of this study demonstrated that nearly two-thirds (64.7%) of patients treated with etanercept had some form of dosage adjustment during their treatment course. Dosage increases were reported most often; all were due to inefficacy of etanercept at the FDA-approved dosing. Interruptions and decreased dosages were reported among 36.4% and 18.2% of patients, respectively. Our study confirms previous data suggesting use of off-label doses of etanercept is commonplace, and a trial of increased etanercept dosing may be worthwhile for biologic-naive patients achieving suboptimal clinical response on standard dosing before switching to another biologic.

Effect of Golimumab Dose Escalation in Japanese Patients With Rheumatoid Arthritis: Post-Hoc Analysis of Post-Marketing Surveillance Data.

IntroductionWhile dose escalation of golimumab has been used for patients with rheumatoid arthritis who demonstrate an inadequate response to the standard dose, its effectiveness has not been fully evaluated. The aim of this study was to assess the clinical outcome observed by dose escalation of golimumab for patients with rheumatoid arthritis in the daily clinical setting.MethodsA post hoc analysis was performed of data from the 24-week post-marketing surveillance conducted in Japan (n = 5154). A total of 301 patients with moderate or high disease activity at baseline who underwent dose escalation of golimumab were assessed for effectiveness at 24 weeks based on several variables, such as DAS28-CRP, SDAI, and CDAI, as well as for medication persistence through 24 weeks. In addition, the study population was stratified by the time to dose escalation, and effectiveness was likewise evaluated. Logistic regression analysis was performed to identify factors associated with a moderate/good EULAR response to golimumab at 24 weeks.ResultsPatients with golimumab dose escalation showed significant improvement of the clinical signs and symptoms of rheumatoid arthritis at 24 weeks, as indicated by reduction of the DAS28-CRP (∆0.89), SDAI (∆8.64), and CDAI (∆8.28) scores. This result was relatively consistent across the subgroups stratified by the timing of dose escalation. According to Kaplan-Meier analysis, 78.1% of the patients continued to receive golimumab at 24 weeks, and this was also similar among the subgroups stratified by the time to dose escalation. Multivariate analysis identified male sex and previous biologic therapy as factors that were significantly associated with the clinical response at 24 weeks.ConclusionIn real-world clinical practice, improvement of disease activity was observed after uptitration of golimumab from 50 to 100 mg regardless of the timing. Male patients and biologic-naive patients were more likely to respond to dose escalation of golimumab.Trial RegistrationUMIN-CTR, Identifier: UMIN000015895.Electronic Supplementary MaterialThe online version of this article (10.1007/s40744-020-00198-4) contains supplementary material, which is available to authorized users.

Effects of successive switches to different biosimilars infliximab on immunogenicity in chronic inflammatory diseases in daily clinical practice

ObjectiveTo evaluatre the risk of immunogenicity in patients with chronic inflammatory diseases who experienced successive non-medical swiches to different biosimilars infliximab. Patients and MethodsObservational study over a 3-year observation period assessing the risk of immunogenicity in i) patients in maintenance therapy with innovator infliximab who were successively switched to CT-P13, then to SB2 (cohort-1) and ii) biologic-naive patients initiated with CT-P13 before being switched to SB2 (cohort-2). A propotion meta-analysis was also performed, integrating our results to 16 additional studies. ResultsCohort-1 included 265 patients who switched to CT-P13, and 140 patients were subsequently switched to SB2. Among the 235 anti-drug antibody (ADA)-free patients at baseline, 20 patients (8.5%) developed ADA over the 3-year observation period (rate of 3 for 100 patient years). Cohort-2 included 44 patients, of whom 29 subsequently switched to SB2. A total of 11 patients (25%) developed ADA within 3 years (rate of 14 for 100 patients years). We found no influence of the number of biosimilars infliximab received on ADA deveopment in both cohorts. The risk of treatment discontinuation was significantly higher in patients with positive ADA in both cohorts. The meta-analysis including our data exposed an incidence of immunogenicity of 4.7% (95% CI 3.5–6.1%) after the switch from innovator infliximab to biosimilar infliximab and 21.1% (95% CI 13.1–30.3%) in patients initiating biosimilar infliximab. ConclusionImmunogenicity was not favored by successive non-medical switches to biosimilars infliximab in our study, but was associated with treatment discontinuation.

Comparative Analysis of 3-Year Persistence With Vedolizumab Compared With Antibodies Against Tumor Necrosis Factor-Alpha in Patients With Inflammatory Bowel Disease in Germany: Retrospective Analysis of a Large Prescription Database.

The goal of the study was to compare persistence with vedolizumab versus adalimumab, golimumab, and infliximab in biologics-naïve patients with inflammatory bowel disease treated in gastroenterological practices and outpatient clinics in Germany. Patients aged 18 or older who had initiated a biological therapy (vedolizumab, infliximab, adalimumab, or golimumab) were included in the present study. Prescriptions between July 2014 and March 2017 of the respective biological drug emerging from gastroenterological practices or outpatient clinics in Germany were retrieved from the longitudinal prescription (LRx) database. Patients treated with vedolizumab were matched with patients treated with infliximab, adalimumab, or golimumab on the basis of age, gender, medication before biologic therapy, and index year. The primary outcome variable of the study was the rate of persistence with vedolizumab compared with antitumor necrosis factor biologics (infliximab, adalimumab, and golimumab) within 3 years of the first prescription in outpatient settings. Kaplan-Meier analysis was performed in 15,984 patients naïve to biologics revealing the statistically lower risk of discontinuation for vedolizumab compared with adalimumab, golimumab, or infliximab. In matched-pairs analyses, within 3 years after the first prescription, 39.5% of 2076 patients were persistent to vedolizumab compared with 33.5% of matched patients persistent to adalimumab (P<0.001). 37.6% of 716 patients were persistent to vedolizumab compared with 24.7% of matched patients persistent to golimumab (P<0.001). 35.7% of 2055 patients were persistent to vedolizumab compared with 30.2% of matched patients persistent to infliximab (P=0.119). Vedolizumab was associated with a significantly lower risk of therapy discontinuation compared with adalimumab [hazard ratio (HR)=0.86; 95% confidence interval (CI), 0.81-0.93] and golimumab (HR=0.60; 95% CI, 0.54-0.67), respectively; the vedolizumab risk of therapy discontinuation was numerically lower than infliximab but statistical significance was not achieved (HR=0.93; 95% CI, 0.85-1.02). In biologics-naïve IBD patients treated in outpatient settings in Germany, matched-pair analyses showed that vedolizumab was associated with significantly improved drug persistence compared with adalimumab or golimumab, whereas numerical improvement was shown in comparison with infliximab.

P405 Comparison of long-term outcomes of infliximab vs. adalimumab in 1488 biologic-naive Korean patients with Crohn’s disease

Abstract Background Data on the comparative effectiveness of infliximab (IFX) or adalimumab (ADA) in patients with Crohn’s disease (CD) are rare, particularly for Asian patients. We compared the clinically key outcomes (surgery, hospitalisation, and corticosteroid use) of these two drugs in biologic-naive Korean patients with CD. Methods Using National Health Insurance claims, we collected data on patients who were diagnosed with CD and exposed to IFX or ADA between 2010 and 2016. Results We included 1488 new users of biologics (1000 IFX users and 488 ADA users). Over a median follow-up of 2.1 years after starting biological therapy, there were no significant differences in the risk of surgery (ADA vs. IFX; adjusted hazard ratio [aHR], 1.30; 95% confidence interval [CI], 0.86–1.95), hospitalisation (aHR, 1.05; 95% CI, 0.84–1.32), and corticosteroid use (aHR, 0.84; 95% CI, 0.58–1.22) between IFX and ADA users. These results were unchanged even when only patients who used biologics for over 6 months were analysed (aHR [95% CI]; surgery: 1.41 [0.88–2.26], hospitalisation: 1.06 [0.83–1.35], and corticosteroid use: 0.82 [0.56–1.21]). Additionally, these results were stable in patients treated with biological monotherapy or combination therapy with immunomodulators. Conclusion In this nationwide population-based study, there was no significant difference in the long-term effectiveness of IFX and ADA in the real-world setting of biologic-naive Korean patients with CD. In the absence of trials to directly compare IFX and ADA, our study supports that the choice of one of these two biologics may be allowed to be determined by the preference of patients and/or physicians.

Switching Biologics in the Treatment of Psoriasis: A Multicenter Experience

Background/Objective: The purpose of our study was to provide evidence on the treatment choices, reasons, and results of switching between biologic agents in treating patients with psoriasis. Methods: We conducted a retrospective database search of six tertiary referral centers for pso­riasis patients between January 2007 and May 2019. We analyzed patient and treatment characteristics of all patients in the registry. Results: We enrolled 427 psoriatic patients treated with biologics, and 145 (34%) required a switch to another biologic. The reasons for discontinuing the first biologic agent were inefficacy (n = 106, 62.4%), adverse events (n = 28, 16.5%), and others (n = 36, 21.2%). At week 12, there was a 67.7% reduction in the Psoriasis Area and Severity Index (PASI) score of patients treated with their first biologic, and 51.4% reduction for the second. A drug survival analysis showed no statistically significant difference between the drug survival of first-line biologic agents, but ustekinumab had the highest survival rate among second-line biologics (log-rank p = 0.010). Multivariate analyses for overall drug discontinuation showed that the occurrence of psoriatic arthritis (OR: 1.883, 95% CI: 1.274–2.782, p = 0.001), nail involvement (OR: 2.334, 95% CI: 1.534–3.552, p < 0.001), and use of concomitant treatment (OR: 2.303, 95% CI: 1.403 –3.780, p = 0.001) are predictors for discontinuation. Conclusion: Discontinuation of treatment was most commonly due to inefficacy. Patients who switched to a different biologic agent showed a similar improvement in PASI scores compared to biologic-naive patients. Switching to a second biologic therapy due to inefficacy or adverse events caused by the first one may improve psoriasis.

P105 Use of Infliximab or Adalimumab in Biologic-Naive Patients With Inflammatory Bowel Disease: Study of Patient Reported Outcomes in IBD Partners

BACKGROUND: We sought to compare Patient-Reported Outcomes Measurement Information System (PROMIS) measures and corticosteroid-free remission in biologic naive individuals with Crohn's disease (CD) or ulcerative colitis (UC) newly initiating therapy with adalimumab (ADA) or infliximab (IFX) in a large cohort of patients with inflammatory bowel disease (IBD). METHODS: Using data from the IBD Partners cohort from April 2014 to July 2019, we performed longitudinal analyses comparing the effects of initiation of ADA or IFX therapy on PROMIS measures and corticosteroid-free remission. We included adult IBD patients who were naive to biologics and who started ADA or IFX within 90 days of their baseline visit. Patients were required to have at least one follow-up visit 91-365 days later. Patients were excluded if they had prior exposure to biologic therapy at baseline, history of ileoanal pouch or end ileostomy, or if they failed to include a start date for initiation of their biologic therapy. We performed bivariate analyses by IFX or ADA subgroup, followed by logistic regression models to investigate factors associated with steroid-free remission, stratified by CD or UC disease subtype. RESULTS: A total of 256 biologic naive patients were included in our study. A total of 170 individuals started ADA (109 (64%) with CD and 61 (36%) with UC). Of the 86 patients initiating IFX, 51 (59%) had CD and 35 (41%) had UC. A majority of patients were female, Caucasian, and had similar mean age and disease duration at baseline. Overall, there were no significant differences at baseline of IBD-related hospitalization, prior IBD-related surgery, concurrent corticosteroid use, or immunomodulator (IMM) use between the ADA and IFX groups. No significant differences in anxiety, depression, fatigue, pain, sleep or social satisfaction were found at follow up between IFX and ADA groups overall, and for UC and CD subgroups. Reported rates of steroid-free remission at follow up were similar between biologic naive UC patients treated with ADA or IFX (37.1% vs 36.2%, P = 0.93). For UC, combination therapy with IFX and IMM had a higher rate of steroid-free remission as compared to IFX alone (53.8% vs 27.3%, P = 0.12), albeit not statistically significant. A similar trend was seen for ADA and IMM as compared to ADA alone (43.9% vs 35.3%, P = 0.20). Among biologic naive CD patients, rates of steroid-free remission at follow up were similar amongst groups (54.9% IFX vs 67.0% ADA, P = 0.14). Rates of steroid-free remission at follow up for combined therapy vs monotherapy were also similar for CD patients. In logistic regression models, only lack of steroid use at baseline was independently associated with steroid-free remission at follow up in CD patients (OR 0.37, 0.17-0.78). CONCLUSION(S): Among this cohort of biologic naive IBD patients, therapy with ADA or IFX resulted in similar rates of corticosteroid-free remission. Other PROs including PROMIS measures of anxiety, depression, fatigue, pain, sleep, and social satisfaction were also similar in ADA vs IFX treated patients. These findings suggest the comparative effectiveness of ADA and IFX are similar.

Comparative Effectiveness of Certolizumab Pegol, Abatacept, and Biosimilar Infliximab in Patients With Rheumatoid Arthritis Treated in Routine Care: Observational Data From the Danish DANBIO Registry Emulating a Randomized Trial.

Nationwide Danish guidelines regarding rheumatoid arthritis (RA) patients initiating biologic treatment (i.e., biologic disease-modifying antirheumatic drugs [DMARDs]) are issued on an approximately annual basis. For biologics-naive patients treated with concomitant methotrexate, mandatory medications included certolizumab pegol (CZP; year 2013-2014, recommended compliance 80%), abatacept (ABA; 2014-2015, 80%), and biosimilar infliximab (CT-P13; 2015-2016, 50%). We hypothesized that these guidelines could be perceived as a surrogate randomization tool in which calendar period rather than patient-specific factors defined the choice of the biologic DMARD. We undertook this study to assess compliance with guidelines (supporting the assumption of surrogate randomization) and to compare the effectiveness of CZP, ABA, and CT-P13 in patients treated according to guidelines. This was an observational cohort study emulating a randomized trial (using intent-to-treat analyses). RA patients compliant with the treatment guidelines were identified in DANBIO, and information on prior comorbidities was obtained by linking to national registries. Outcome measures included remission rates according to the Disease Activity Score in 28 joints (DAS28) (at 6 and 12 months) and treatment retention at 1 year, compared across treatment regimens. Comorbidity/confounder-adjusted multivariable logistic and Cox regression analyses were used. Seven hundred seventy-six patients were included in the study (336 receiving CZP, 215 receiving ABA, 225 receiving CT-P13). Compliance with treatment guidelines was high: 70%, 65%, and 59%, respectively. Six-month DAS28 remission rates were 35%, 33%, and 42%, and 12-month rates were 35%, 31%, and 35%, respectively. Compared to CZP, adjusted odds ratios for 6- and 12-month DAS28 remission rates were 0.96 (95% confidence interval [95% CI] 0.63-1.47) and 0.74 (95% CI 0.47-1.15) for ABA and 1.38 (95% CI 0.91-2.09) and 0.96 (95% CI 0.62-1.49) for CT-P13, respectively. Adjusted hazard ratios for withdrawal (during days 0-90 and days 91-365) were 0.70 (95% CI 0.39-1.27) and 1.16 (95% CI 0.84-1.60) for ABA and 0.58 (95% CI 0.33-1.10) and 0.83 (95% CI 0.59-1.17) for CT-P13, respectively, compared to CZP. The surrogate randomization procedure enabled head-to-head comparisons of CZP, ABA, and CT-P13. Although some differences in estimated effectiveness were observed across drugs, confidence intervals were wide and statistical significance was not reached.

Risk of major cardiovascular events in patients with psoriasis receiving biologic therapies: a prospective cohort study.

BackgroundThe cardiovascular safety profile of biologic therapies used for psoriasis is unclear.ObjectivesTo compare the risk of major cardiovascular events (CVEs; acute coronary syndrome, unstable angina, myocardial infarction and stroke) in patients with chronic plaque psoriasis treated with adalimumab, etanercept or ustekinumab in a large prospective cohort.MethodsProspective cohort study examining the comparative risk of major CVEs was conducted using the British Association of Dermatologists Biologics and Immunomodulators Register. The main analysis compared adults with chronic plaque psoriasis receiving ustekinumab with tumour necrosis‐α inhibitors (TNFi: etanercept and adalimumab), whilst the secondary analyses compared ustekinumab, etanercept or methotrexate against adalimumab. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using overlap weights by propensity score to balance baseline covariates among comparison groups.ResultsWe included 5468 biologic‐naïve patients subsequently exposed (951 ustekinumab; 1313 etanercept; and 3204 adalimumab) in the main analysis. The secondary analyses also included 2189 patients receiving methotrexate. The median (p25–p75) follow‐up times for patients using ustekinumab, TNFi, adalimumab, etanercept and methotrexate were as follows: 2.01 (1.16–3.21), 1.93 (1.05–3.34), 1.94 (1.09–3.32), 1.92 (0.93–3.45) and 1.43 (0.84–2.53) years, respectively. Ustekinumab, TNFi, adalimumab, etanercept and methotrexate groups had 7, 29, 23, 6 and 9 patients experiencing major CVEs, respectively. No differences in the risk of major CVEs were observed between biologic therapies [adjusted HR for ustekinumab vs. TNFi: 0.96 (95% CI 0.41–2.22); ustekinumab vs. adalimumab: 0.81 (0.30–2.17); etanercept vs. adalimumab: 0.81 (0.28–2.30)] and methotrexate against adalimumab [1.05 (0.34–3.28)].ConclusionsIn this large prospective cohort study, we found no significant differences in the risk of major CVEs between three different biologic therapies and methotrexate. Additional studies, with longer term follow‐up, are needed to investigate the potential effects of biologic therapies on incidence of major CVEs.

Development and Validation of a Test to Monitor Endoscopic Activity in Patients With Crohn’s Disease Based on Serum Levels of Proteins

Noninvasive tests to measure endoscopic activity in patients with Crohn's disease (CD) have limitations. We aimed to develop a test to identify patients in remission, based on endoscopic analysis, and monitor CD activity based on serum levels of proteins. We developed a test to measure 13 proteins in blood (ANG1, ANG2, CRP, SAA1, IL7, EMMPRIN, MMP1, MMP2, MMP3, MMP9, TGFA, CEACAM1, and VCAM1), called the endoscopic healing index [EHI], using samples from 278 patients with CD from a multinational training cohort. We validated the test using 2 independent cohorts of patients with CD: 116 biologic-naive patients with early-stage CD (validation cohort 1) and 195 biologic-exposed patients with chronic CD (validation cohort 2). The ability of the test to identify patients with active disease vs patients in remission (defined as a simple endoscopic score for CD of ≤2 and ≤1 in each segment, or a total CD endoscopic index of severity score <3) was assessed by using area under receiver operating characteristic curve (AUROC) analysis. The diagnostic accuracy of the test was compared with that of measurement of serum C-reactive protein (CRP) and fecal calprotectin. The EHI scores range from 0 to 100 units; higher scores indicate more severe CD activity, based on endoscopy findings. The EHI identified patients in remission with an AUROC of 0.962 in validation cohort 1 (95% confidence interval, 0.942-0.982) and an AUROC of 0.693 in validation cohort 2 (95% confidence interval, 0.619-0.767), regardless of CD location or phenotype. A cutoff value of 20 points identified patients in remission with the highest level of sensitivity (97.1% in validation cohort 1 and 83.2% in validation cohort 2), with specificity values of 69.0% and 36.6%, respectively. A cutoff value of 50 points identified patients in remission with the highest level of specificity (100% in validation cohort 1 and 87.8% in validation cohort 2), with sensitivity values of 37.3% and 30.0%, respectively. The EHI identified patients in remission with a significantly higher AUROC value than the test for CRP (0.876, P < .001 in validation cohort 1 and 0.624, P= .109 in validation cohort 2). In analysis of patients with available FC measurements, the AUROC value for the EHI did not differ significantly from that of measurement of FC (AUROC, 0.950 for EHI vs AUROC, 0.923 for FC; P= .147 in validation cohort 1 and AUROC, 0.803 for EHI vs AUROC, 0.854 for FC; P= .298 in validation cohort 2). We developed an index called the EHI to identify patients with CD in endoscopic remission based on blood levels of 13 proteins. The EHI identified patients with resolution of endoscopic disease activity, with good overall accuracy, although with variation between the 2 cohorts assessed. The EHI AUROC values were comparable to measurement of FC and higher than measurement of serum CRP. The test might be used in practice to assess endoscopic activity in patients with CD.

PMS31 COST-EFFECTIVENESS ANALYSIS OF SECUKINUMAB IN ANKYLOSING SPONDYLITIS IN BIOLOGIC-NAIVE PATIENTS FROM THE PORTUGUESE PERSPECTIVE

Biologic therapy has been successfully adopted for the treatment of patients with ankylosing spondylitis (AS). Several biologics are currently licensed in AS in Portugal including etanercept, infliximab, adalimumab, golimumab, certolizumab pegol and secukinumab. We aimed to assess the cost-effectiveness of secukinumab in AS biologic-naive patients from the Portuguese National Healthcare Service (NHS) perspective. A decision analytic model (semi-Markov) was developed to evaluate the cost-effectiveness of secukinumab 150mg over a lifetime horizon (60 years) against other biologics, with the exception of infliximab, which is not a first-line anti-TNF in the context of the Portuguese current clinical practice. Model clinical inputs (short- and long-term changes in Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] and in Bath Ankylosing Spondylitis Functional Index [BASFI], withdrawal rates, adverse events, resource use, costs, utilities and disutilities) were obtained from clinical trials, literature and expert’s opinion, and national official sources. Benefits were expressed as quality-adjusted life years (QALYs). Costs were expressed in 2019 Euros. Incremental cost per QALY gained was estimated considering an annual discount rate of 5% for costs and benefits. Sensitivity analyses were performed. Over a lifetime horizon, the model predicted that patients treated with secukinumab 150mg achieve the highest benefit (10.03 QALYs) at the lowest cost (€191,182) versus etanercept (9.28 QALYs; €214,547), adalimumab (9.59 QALYs; €206,259), certolizumab (9.72 QALYs; €214,373) and golimumab (9.94 QALYs; €211,435). Therefore, secukinumab dominated all comparators. In all treatments, about half of the cost is related with the acquisition of the biologic drug. Probabilistic sensitivity analysis showed that secukinumab demonstrated higher probability of achieving maximum net monetary benefit versus comparators at a threshold of €30,000/QALY. This analysis indicates that secukinumab is the most cost-effective treatment option for biologic-naive AS patients in Portugal. Treatment of AS with secukinumab may thus result in relevant benefits for patients and higher efficiency for the NHS.

PSS15 REAL-WORLD COSTS IN BIOLOGIC NAIVE PSORIATIC ARTHRITIS PATIENTS INITIATING APREMILAST OR BIOLOGICS IN A US HEALTHCARE CLAIMS DATABASE

Psoriatic arthritis (PsA) is a chronic inflammatory disorder. Information on real-world healthcare costs associated with apremilast and biologic therapy in PsA is limited. This study examined healthcare costs among biologic-naive PsA patients who initiated treatment with apremilast or a biologic. Adult patients with PsA were identified if they initiated treatment with either apremilast, a tumor necrosis factor (TNF) inhibitor (adalimumab, certolizumab, etanercept, golimumab, infliximab) or an interleukin (IL) inhibitor (ixekizumab, secukinumab, ustekinumab) between January 1, 2015, and December 31, 2016, and had a minimum of 12 months pre-index and post-index continuous enrollment in the Truven Health (now IBM Watson Health) MarketScan® Commercial and Medicare Supplemental Database. The study used 1:2 propensity score matching between apremilast and biologic patients based on available demographics and clinical characteristics. Total healthcare costs were measured by type of service (inpatient, outpatient and outpatient pharmacy) and were based on paid amounts of adjudicated claims. Costs were reported at 6, 12 and 18 months post-index. T-test, Wilcoxon rank-sum test and chi-squared test were used to evaluate differences between the apremilast and biologic cohorts for continuous and categorical variables, as appropriate. In all, 1,471 biologic-naive PsA patients initiating apremilast were matched to 890 biologic-naive PsA patients initiating biologics (TNF: n=804; IL: n=86). Patient characteristics were similar between the 3 cohorts (mean age: 50 years; Charlson Comorbidity Index score: 0.58 [apremilast], 0.55 [TNF], 0.56 [IL]). Twelve-month total costs were significantly lower among apremilast initiators vs TNF and IL initiators ($39,854 vs $57,243 and $65,867; both P<0.0001). Outpatient pharmacy costs were significantly lower for apremilast patients vs TNF and IL patients ($29,130 vs $48,540 and $57,038; P<0.0001). Similar results were seen at 6 and 18 months post-index. Biologic-naive PsA patients initiating apremilast had significantly lower healthcare costs than patients initiating biologics in a US claims database.

PBI20 SECUKINUMAB VS. ADALIMUMAB AND INFLIXIMAB FOR THE TREATMENT OF ANKYLOSING SPONDYLITIS: A COST PER RESPONDER ANALYSIS AT 52 WEEKS FROM A GREEK PERSPECTIVE

This analysis estimated and compared long-term Cost Per Responder (CPR) based on the ASAS outcomes following 52 weeks treatment for ankylosing spondylitis (AS) with Secukinumab (SEC), compared to Adalimumab (ADA) and Infliximab (INF) for Greek NHS Analysis is based on a matching-adjusted indirect comparison (MAIC). CPR calculated using long-term response rates from MAIC based on MEASURE 2, ATLAS & ADEPT RCTs. The CPR was estimated by dividing drug acquisition cost for the course of treatment with its response rate. Drug costs were based on December 2017 price bulletin and the number of doses required for 52 weeks. (infliximab administration cost also estimated). MAIC showed that ASAS response rates were significantly higher for SEC compared to ADA at 52 weeks. ASAS20 response rates were 81% vs 65%, ASAS40 response rates were 62% vs. 47% and ASAS5/6 response rates were 72% vs. 55% for SEC and ADA, respectively. The CPR for ASAS20 responders were €7,073 vs. €10,139, for ASAS40 responders were €9,195 vs. €14,096 & for ASAS5/6 responders were €7,918 vs. €12,061 for SEC and ADA, respectively. The CPR for ASAS20/40/5/6 responders were 34%/38%/38% lower, respectively, for SEC compared to ADA. ACR20 response rates were 91% vs. 69% & ASAS5/6 response rates were 33% vs. 23% for SEC and INF, respectively. CPR for ACR20 responders were €6,298 vs. €16,046 & for ASAS5/6 responders were €17,281 vs €47,746 for SEC and INF, respectively. Sensitivity analyses confirmed results robustness. The CPR for all ASAS outcomes at 52 weeks were consistently lower for SEC vs. ADA and INF, leading to important savings for Greek Social Security Fund . These findings indicate that may be more efficient treat AS biologic naive patients in Greece with SEC vs. ADA or INF. A potential weakness is that the comparison between drugs is indirect and based on a statistical model.

847 Real World Experience of Ustekinumab for Induction and Maintenance of Remission in Crohn’s Disease: A U.K. Single Center Experience

INTRODUCTION: Ustekinumab(UST),an IgG1 monoclonal antibody targeting IL12/IL23(p40 sub-unit)has been licensed in UK for use in moderate to severe Crohn’s disease(CD) since 2017.We present a real -world experience from our center. METHODS: A retrospective analysis of patients commenced on UST was conducted using electronic medical records to evaluate efficacy. Patients were assessed at baseline, induction (week 8) and at 1 year. Our primary end point was reduction in Physicians global assessment (PGA). Secondary endpoints were improvement in CRP (&gt;10 at baseline), Fecal Calprotectin (&gt;250 at baseline) and albumin (&lt;35 at baseline). Concomitant medication and surgical history were also recorded. RESULTS: 62 patients received UST (42 female; mean age 44.74). Mean age at diagnosis was 33.61 years and average duration of disease was 135 months (median 180, IQR 135.25). Sixteen patients had previous surgery for CD. At baseline 95% patients had PGA of moderate to severe disease with 54 (87%) achieving primary endpoint at induction. 16 patients had annual follow up and 81.25% achieved the primary endpoint. The Harvey Bradshaw index at follow up appointments correlated with the PGA values to account for clinical remission. From baseline to induction, 24 had CRP &gt;10. Of these, 20 (83.3%) patients achieved the secondary endpoint for CRP at induction. At annual follow up 15 patients had CRP recorded, 7 out of them had CRP &gt;10 at baseline and all achieved the secondary endpoint. Albumin was &lt; 35 in 21 patients at baseline and 71.5% showed improvement at induction. At 12 months eight of the above 21 had albumin recorded and 5 achieved the secondary endpoint of improvement in albumin. Fecal calprotectin was elevated in 19 out 47 patients recorded at baseline. Of whom 58% achieved the secondary endpoint. 53 patients (85.5%) had received a previous biologic with 20 receiving Infliximab (IFX), adalimumab (ADA) and vedolizumab (VDZ) prior to UST.15 received only IFX, 11 only ADA and 20 both anti-TNF’s. One patient received IFX and VDZ. Four adverse reactions were noted, 2 had rash after infusion and 1 headache. One patient reported epidydimo-orchitis 7 days post infusion and required hospitalisation. Twelve patients discontinued UST with 6 having surgery and 6 from loss of response (5 secondary and 1 primary loss of response). CONCLUSION: UST is effective in induction well as maintenance of remission in CD for biologic experienced and naive patients as also in those with previous surgical resection.There were no significant safety concerns.

Treatment patterns and healthcare costs among biologic-naive patients initiating apremilast or biologics for the treatment of psoriatic arthritis: results from a US claims analysis

Objective: Information on treatment costs for psoriatic arthritis (PsA) can be valuable for payers and providers who make treatment and formulary decisions. This study compared real-world treatment patterns and healthcare costs among biologic-naive patients with PsA initiating apremilast or biologics.Methods: A retrospective cohort study was conducted using the Optum Clinformatics™ claims database. The study included biologic-naive patients with PsA who initiated treatment with apremilast or a biologic between 1 January 2014, and 31 December 2015. Propensity score matching was used to adjust for selection bias. Treatment persistence/adherence and all-cause healthcare costs were evaluated. Cost differences were determined using Wilcoxon rank-sum tests.Results: In all, 125 biologic-naive patients initiating treatment with apremilast were matched to 245 biologic-naive patients initiating treatment with a biologic. Twelve-month treatment persistence was similar for apremilast vs. biologic users (43.2 vs. 36.7%; p = .2277). While persistent on treatment for up to 12 months, total healthcare costs (from all utilizations) were significantly lower among apremilast vs. biologic users ($28,130 vs. $37,093; p < .0001). Likewise, per-patient per-month costs while persistent on treatment were significantly lower among apremilast vs. biologic users whether they switched treatments ($2,455 vs. $3,497; p = .0103), remained persistent on treatment ($2,434 vs. $3,521; p < .0001), or discontinued but did not switch treatments ($2,178 vs. $2,696; p = .0082).Conclusions: Apremilast patients had significantly lower healthcare costs than biologic patients, even when they switched to a biologic, during the 12-month post-index period. These results may be useful to payers and providers seeking to optimize PsA care while reducing healthcare costs.

Defining response to TNF-inhibitors in rheumatoid arthritis: the negative impact of anti-TNF cycling and the need for a personalized medicine approach to identify primary non-responders

Current guidelines recommend treating rheumatoid arthritis (RA) patients to reach low disease activity or remission, however, most biologic-naive RA patients fail to reach treatment targets on their first biologic therapy. Approximately 90% of biologic-naive RA patients receive a tumor necrosis factor alpha inhibitor (anti-TNF) as their first biologic treatment, even though several alternative mechanism of action (MOA) therapies are approved as first-line options. After 3 months of therapy, patients may remain on anti-TNF therapy even if they fail to achieve the treatment target, mainly due to formulary structures. This means patients have to endure a second and even a third ineffective anti-TNF—called anti-TNF cycling—before changing MOA. This significantly delays patients from reaching their treatment targets. All anti-TNF drugs target the same molecular and inflammatory pathways; thus, it is not surprising that most patients who are primary non-responders to their initial anti-TNF therapy fail to achieve their treatment targets when cycled through alternative anti-TNFs. This suggests that primary non-responders should be switched to an alternative MOA therapy rather than enduring anti-TNF cycling. Avoiding anti-TNF cycling would prevent disease progression and improve quality of life for RA patients who are primary non-responders to anti-TNFs. The development of a personalized medicine approach to identify primary non-responders to anti-TNFs prior to treatment would allow significantly more patients to reach their treatment target by treating them with alternative MOA therapies as first-line therapies.

Reduction in the utilization of prednisone or methotrexate in Canadian claims data following initiation of etanercept in pediatric patients with juvenile idiopathic arthritis

BackgroundIn adult patients with arthritis, use of the tumor necrosis factor (TNF) inhibitor etanercept (ETN) is often associated with a reduction in the utilization of co-medications, particularly steroids. Comparatively little is known about the utilization of co-medications when ETN is initiated in pediatric patients with juvenile idiopathic arthritis (JIA).MethodsThis study analyzed Canadian longitudinal claims level data spanning January 2007 to April 2017. Data were collated from the IQVIA Private Drug Plan, Ontario Public Drug Plan, and the Quebec Public Drug Plan (Régie de l’assurance maladie du Québec) databases. Patients < 18 years of age were indexed when filling a prescription for ETN between January 2008 and January 2016. Those who met the inclusion and exclusion criteria were assessed for methotrexate (MTX), and prednisone (PRD) use in the 6 months prior to and 12 months following initiation of ETN.ResultsLongitudinal claims data for 330 biologic-naive pediatric patients initiating ETN therapy were included. The majority of patients were female (67%), aged 10–17 years (64%), and with a drug history consistent with JIA (96%). Most patients were from Quebec (36%) or Ontario (33%). Dosing of ETN was weight-based with a mean dosage over the first year of 31 mg per week. ETN dosing was relatively consistent over the first year. In total, 222 (67%) patients did not use MTX and 223 (68%) did not use PRD before or after starting ETN. A total of 17% (18/103) of MTX-treated and 50% (46/92) of PRD-treated patients discontinued use of those medications upon initiation of ETN treatment. In patients continuing MTX or PRD, significant reductions in the weekly dosage from 14.3 to 6.8 mg per week for MTX and from 56 to 23 mg per week for PRD were observed (P < 0.01).ConclusionsThis study of Canadian claims-level data is the first large prespecified analysis of co-medication utilization following the initiation of ETN therapy in pediatric patients. A decline in both MTX and PRD use and dosage was observed and may be associated with benefits related to safety, tolerability, and overall healthcare costs.

A real life experience with novel biosimilar InfimabTM in biologic naive patients with active rheumatoid arthritis

A real life experience with novel biosimilar InfimabTM in biologic naive patients with active rheumatoid arthritis