Biologic Therapy For Psoriatic Arthritis Research Articles

'Double target' ultrasound monitoring of biologic therapy in psoriatic arthritis.

We aimed to 1) evaluate by power Doppler (PD) ultrasound (US) the response to therapy of the most inflamed joint and enthesis (target sites) in psoriatic arthritis (PsA) patients starting a biologic disease-modifying anti-rheumatic drug (bDMARD); and 2) to investigate the correlation between the US response and clinical data. Consecutive PsA patients with US synovitis and US 'active' enthesitis, starting a bDMARD, were included. The joint with the highest OMERACT-EULAR-US composite score and the enthesis with the highest PD grade (targets) were identified at baseline. The US examination and clinical assessment were performed at 0, 3 and 6 months. The response of OMERACT-EULAR-US synovitis composite score was defined as reaching a grade = 0 at follow-up examination; synovial and entheseal PD responses were defined as a PD=0 and/or a reduction of ≥2 PD grades at follow-up examination. Thirty patients were included. Synovitis composite score, synovial PD and entheseal PD showed significant responses at 3 and 6 months compared to baseline (p<0.01). Synovial PD responses were higher than entheseal PD responses at 3 months (71.4% vs 40.0%, p=0.01) and 6 months (77.8% vs. 46.7%, p=0.02). US synovitis responses were correlated with DAPSA (p<0.01) and MDA responses (p=0.01 for composite score, p=0.02 for PD). US was found sensitive for monitoring treatment response in PsA patients starting a biologic drug. Entheseal PD was less responsive than synovial PD, suggesting that enthesitis may represent a 'difficult-to-treat' domain in PsA.

Effects of TNF-α inhibition versus secukinumab on active ultrasound-confirmed enthesitis in psoriatic arthritis.

Enthesitis is a hallmark of psoriatic disease, but its clinical assessment is problematic in terms of diagnostic sensitivity and overlap with other comorbid conditions. Ultrasound is a useful tool that can give a more detailed assessment of enthesitis. Research demonstrates that those with persistent ultrasound entheseal disease are at risk of progressive articular damage. With limited data to guide choice between biologic therapy for psoriatic arthritis (PsA) patients, we wanted to assess the response of ultrasound-confirmed enthesitis to different forms of biologic therapies and study its utility in making more informed decisions. This was an open label observational study including patients aged ⩾18 years, who fulfil the classification criteria for PSA (CASPAR) and were due to commence on their first biologic therapy. The primary outcome was the change in MAdrid Sonographic Enthesitis Index (MASEI) score at 16 weeks of treatment. The MASEI score was also modified to assess the active elementary lesions (ActiveMASEI). In all, 80 PsA patients were enrolled with 75 patients completing the study [secukinumab n = 23 and tumour necrosis factor inhibitor (TNFi) n = 52]. The mean reduction in MASEI score after 16 weeks of treatment was 3.42 with TNFi versus 1.74 with secukinumab (p = 0.097). There was a significant difference in the change in the MASEIActive score for TNFi versus secukinumab (4.37 versus 2.26; p = 0.030) and this difference was more pronounced when only power Doppler signal within 2 mm of the enthesis insertion was included (4.37 versus 2.00; p = 0.007). Clinical outcomes were similar for both classes of biologic apart from a significant reduction in regards to the Dermatology Life Quality Index and Psoriasis Area and Severity Index score with secukinumab versus TNFi. We have for the first time compared the effect of ultrasound-confirmed enthesitis between different forms of biologic therapies for PsA. We have seen an overall improvement in entheseal scores for both classes of medications and demonstrated a larger reduction in active entheseal disease for TNFi versus secukinumab that merits further exploration.

Long-term survival of biological therapy in psoriatic arthritis: 18-year analysis of a cohort in a tertiary hospital.

To study retention of biologic disease-modifying anti-rheumatic drugs (bDMARDs) or apremilast and potential predictors of lack of response in patients with psoriatic arthritis (PsA). A single-center retrospective analysis of PsA patients who received ≥ 1 bDMARD or apremilast during 2000-2018. The main endpoint was lack of response (primary or secondary failure). Analyses included retention of DMARDs (Kaplan-Meier curves) and potential predictors of lack of response (bivariate and multivariate logistic regression models). A total of 159 patients with PsA received up to 8 DMARDs: etanercept (34%), adalimumab (30%), infliximab (9%), golimumab (9%), apremilast (7%), ustekinumab (5%), certolizumab (4%), and secukinumab (2%). Therapy was discontinued in 96 cases (60%), mainly owing to secondary failure (37%), followed by primary failure (25%) and adverse effects (24%). Retention was analyzed based on 313 units of analysis. Duration of follow-up was 846.1 treatment-years (maximum 14.8years, median 2.75years). A total of 172 DMARDs were discontinued. The probability of continuing the initial treatment was 37% at 5years, 22% at 10years, and 12% at 14years. The longest medium retention time was observed for infliximab (6.2years) and etanercept (4.5years). Predictors of lack of response included male sex, number of swollen joints, and, especially, depression (OR = 35.2). The sensitivity and specificity of the model were 86.4% and 85.7%, respectively, with a coefficient of determination (R2) of 45.6 (ROC, 0.912). Rates of discontinuation due to primary and secondary failure are high in PsA. Retention is better for anti-TNF agents than for other agents.

POS0976 ANALYSIS OF BIOLOGIC THERAPY RETENTION RATE IN PSORIATIC ARTHRITIS PATIENTS WITH AND WITHOUTV AXIAL INVOLVEMENT. DATA FROM CLINICAL PRACTICE

Background:Limited data are available on retention rates of biologic therapy in psoriatic arthritis (PsA) patients (pts) with axial involvement. It has been shown that in the subset of pts with prevalent axial involvement (AS versus PsA and AxSpA versus PsA) a longer duration of anti-TNF-α-therapy was observed as compared to peripheral arthritis [1].Objectives:To compare retention rates of biologic therapy in PsA pts with and without axial involvement in routine clinical practice.Methods:731 pts with PsA according to CASPAR criteria were included in the study. Data were collected from 43 rheumatology clinics over various regions of the Russian Federation. Among the pts, 243 (33.0%) (M/F 132/111) were given biologic therapy. Pts’ age 45.9±12.8 years (yrs), disease duration 8.6±6.5 yrs. Pts underwent standard clinical examination of PsA activity and were split into two groups (gr.), with and without axial PsA (axPsA): axPsA(+) and axPsA(-). Pts in the axPsA(+) gr. had inflammatory back pain by ASAS criteria and/or radiographic sacroiliitis (SI) (unilateral grade≥3 or bilateral grade≥2) and/or active MRI SI and/or typical of axPsA changes of the cervical and/or lumbar spine (marginal/paramarginal syndesmophytes, ankylosis of the facet joints). Pts in the axPsA(-) gr. had only peripheral arthritis. The axPsA(+) gr. included 143 (58.8%) pts, the axPsA(-) gr. 100 (41.2%) pts. 163 (67.1%) pts were treated with TNF inhibitors (TNF-i), 80 (32.9%) pts with interleukin inhibitors (IL-i): 55 pts with Ustekinumab, 25 pts with Secukinumab. During the TNF-i treatment courses Infliximab was given to 34 pts, Adalimumab to 53 pts, Etanercept to 36 pts, Golimumab to 27 pts and Certolizumab Pegol to 8 pts. The observation period lasted 12 months. Treatment retention rates were analyzed using Kaplan-Meier curves and the log-rank test.Results:Analysis of the treatment retention rates revealed statistically significant differences between the axPsA(+) and the axPsA(-) grs. After 12 months of observation, 72.9% of pts in the axPsA(-) gr. continued receiving biologic therapy, while in the axPsA(+) gr. only 53.1% of pts (р=0.0027) received it. The same kind of differences in anti-TNF therapy were found between the axPsA(-) gr. and the axPsA(+) gr.: 82.2% and 62.3% pts respectively (р=0.011) continued receiving TNF-i after 12 months. However no statistically significant differences were found between the two grs. in the treatment retention rates of IL-i therapy: after 12 months of observation 55.5% of axPsA(-) pts and 37% of axPsA(+) pts (р=0.086) continued receiving IL-i.Conclusion:In routine clinical practice, retention rates of biologic therapy were found to be worse in PsA pts with axial involvement. In clinical practice, TNF-i are prescribed twice as often than IL-i. However, considering the need of personalized therapy, in case of axPsA the use of IL-i is preferable because their treatment retention rates don’t depend on axial involvement.

Treatment persistence of biologics among patients with psoriatic arthritis

BackgroundPersistence of biologic therapy in psoriatic arthritis (PsA) patients is an important factor in individualized patient treatment planning and healthcare policy and guideline development.ObjectiveTo estimate the persistence of biologic agents prescribed to PsA patients in a real-life setting as well as factors associated with improved biologic drug survival in these patients.MethodsPatients with PsA from a large healthcare provider database with at least two consecutive dispensed prescriptions of a biologic agent indicated for PsA from January 1, 2002, until December 31, 2018, were identified and followed until medication stop date or the end of observation period. Patients were considered non-persistent whenever a permissible lag time of 6 months from the time of prescription issuance until medication filling date was exceeded. Treatment changes were based on physician decisions and patient preferences.Demographic data including age, sex, body mass index (BMI), ethnicity, smoking history, and socioeconomic status as well as Charlson comorbidity index were retrieved. Data regarding use of steroids and conventional disease-modifying anti-rheumatic drugs (cDMARDs) were also extracted. Descriptive statistics, including means (standard deviations) for continuous variables and frequencies (%) for categorical variables, were used. Persistence estimates were derived using non-parametric survival analysis using Kaplan-Meier functions, with treatment discontinuations as failure events. Cox regression hazard ratio models were conducted to investigate factors associated with drug persistence.ResultsA total of 2301 PsA patients with 2958 treatment periods were identified and included in the analyses. Mean age of the study population was 50.9 ± 14 years, 54% were females, 70.4% were with BMI > 25, 40% were current smokers, and 76% were with a Charlson comorbidity index > 1. The most commonly prescribed drug was etanercept (33%), followed by adalimumab (29%), golimumab (12%), secukinumab (10%), ustekinumab (8%), and infliximab (8%). While approximately 40% of patients persisted on therapy following 20 months of treatment, only about 20% of patients remained on any particular biologic agent after 5 years. Analyzing the data for all treatment periods while taking into account all lines of therapy revealed that secukinumab had a higher persistency than adalimumab, infliximab, and ustekinumab, with a log rank of 0.022, 0.047, and 0.001, respectively. Female sex and smoking were associated with lower drug persistence (HR = 1.25, 95% CI = 1.13–1.38 and HR = 1.109, 95% CI = 1.01–1.21, respectively). On analyzing the data using only the first indicated biologic line, no superiority of any single anti-tumor necrosis factor-alpha (anti-TNFα) agent was observed, while secukinumab was found to be superior as second line therapy to adalimumab, etanercept, infliximab, and ustekinumab but not to golimumab with a log rank P value of 0.001, 0.004, 0.025, and 0.002, respectively.ConclusionsIn this large observational cohort studied in the era of biologic therapy, a relatively low drug persistence was observed, with female sex and smoking having a negative impact on persistency. None of the anti-TNFα agents was found to be more persistent than others as first line therapy, while secukinumab was found to be superior to other biologics when indicated as second line of therapy.

Long-term remission and biologic persistence rates: 12-year real-world data

BackgroundBiologic therapies have greatly improved outcomes in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Yet, our ability to predict long-term remission and persistence or continuation of therapy remains limited. This study explores predictors of remission and persistence of the initial biologic therapy in patients after 12 years. Furthermore, outcomes with adalimumab and etanercept are compared.Patients and methodsRA and PsA patients were prospectively recruited from a biologic clinic. Outcomes on commencing therapy, at 1 year and 12 years were reviewed. Demographics, medications, morning stiffness, patient global health score, tender and swollen joint counts, antibody status, CRP and HAQ were collected. Outcomes at 1 year and 12 years are reported and predictors of biologic persistence and EULAR-defined remission (DAS28-CRP < 2.6) are examined with univariate and multivariate analysis.ResultsA total of 403 patients (274 RA and 129 PsA) were analysed. PsA patients were more likely to be male, in full-time employment and have completed higher education. PsA had higher remission rates than RA at both 1 year (60.3% versus 34.5%, p < 0.001) and 12 years (91.3% versus 60.6%, p < 0.001). This difference persisted when patients were matched for baseline disease activity (p < 0.001). Biologic continuation rates were high for RA and PsA at 1 year (49.6% versus 58.9%) and 12 years (38.2% versus 52.3%). In PsA, patients starting on etanercept had lower CRP at 12 years (p = 0.041). Multivariate analysis showed 1-year continuation [OR 4.28 (1.28–14.38)] and 1-year low-disease activity [OR 3.90 (95% CI 1.05–14.53)] was predictive of a 12-year persistence. Persistence with initial biologic at 12 years [OR 4.98 (95% CI 1.83–13.56)] and male gender [OR 4.48 (95% CI 1.25–16.01)] predicted 12 year remission.ConclusionsThis is the first study to show better response to biologic therapy in PsA compared to RA at 12 years. Long-term persistence with initial biologic agent was high and was predicted by biologic persistence and low-disease activity at 1 year. Interestingly, PsA patients had higher levels of employment, educational attainment, and long-term remission rates compared to RA patients.

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.

Psoriatic arthritis: combinational therapy of biologics and methotrexate - What do we know?

Psoriatic arthritis (PsA) is a systemic inflammatory disease characterized by musculoskeletal involvement mostly associated with skin psoriasis. PsA is associated with significant morbidity and disability, and thus constitutes a major socioeconomic burden. For therapeutic strategies, early diagnosis and sufficient treatment lead to the best outcome with prevention of structural damage and loss of function. The combination of biologics (e.g., tumor necrosis factor inhibitors) and methotrexate (MTX) shows a significantly stronger clinical effect in the treatment of rheumatoid arthritis compared to biologic monotherapy as demonstrated by randomized controlled clinical trials. However, the influence of concomitant MTX on biologic therapy for PsA has not yet been fully clarified due to the lack of data from controlled studies that directly compare both treatment strategies, biologic monotherapy and combination of biologic and MTX. Moreover, data from subgroup analyses, register studies and from non-interventional clinical trials show discrepant results. The Germany-wide MUST study is a placebo-controlled, multicenter, randomized study to investigate the influence of MTX on the efficacy, safety and adherence to biologic therapy with ustekinumab in patients with active PsA. The aim of the study is to evaluate whether MTX naive patients would achieve a greater disease improvement with the combination of MTX and biological therapy than with a biologic monotherapy and whether MTX patients who, in addition to MTX, start a biologic therapy would become worse if MTX is discontinued. Data from randomized and controlled clinical trials are important to better understand the role of MTX as a concomitant medication in patients with PsA. The MUST study offers the ideal opportunity to investigate this question in a controlled study and to find out whether the addition of MTX to ustekinumab therapy is beneficial for patients. The results of this and other studies could improve PsA treatment by potentially omitting additional, possibly ineffective, medication that might increase the risk of adverse reactions. This article gives an overview of the current knowledge and published data regarding the effect of MTX as additional therapy to biological treatments in PsA patients. Additionally, the article introduces current efforts to evaluate the role of MTX for PsA treatment, including the MUST study.

Discovery and confirmation of a protein biomarker panel with potential to predict response to biological therapy in psoriatic arthritis

ObjectiveBiological therapies, which include antitumour necrosis factor-α and T-cell inhibitors, are potentially effective treatments for psoriatic arthritis (PsA) but are costly and may induce a number of side effects. Response...

Biologic Therapy for Psoriatic Arthritis or Moderate to Severe Plaque Psoriasis: Systematic Review with Pairwise and Network Meta-Analysis

Background: A comprehensive assessment of the risk-benefit profile of biologic agents in psoriasis is lacking. We conducted a network meta-analysis of randomized trials on biologic agents in psoriasis. Methods: Trials on biologic agents in psoriasis (including psoriatic arthritis) were sought in several databases. Endpoints were ≥75% Reduction in the Psoriasis Area and Severity Index (PASI75), ≥20% improvement in the American College of Rheumatology core set of outcomes (ACR20), serious adverse events (SAE), and adverse events (AE) at the longest available non-cross-over follow-up. Random-effect methods were used to obtain pairwise and network pooled estimates. Results: A total of 52 trials with 17,617 patients and 9 different biologic agents included, with 52% affected by psoriatic arthritis. After an average follow-up of 18 weeks, treatment with placebo was associated with a 5.9% (5.2%-6.6%) rate of PASI75, 17.4% (15.1%-19.6%) of ACR20, 2.4% (1.9%-2.8%) of SAE, and 51.8% (50.2%-53.4%) of AE. Several biologic agents provided higher PASI75 rates than placebo, with golimumab yielding the most favorable results (relative risk [RR]=14.02 [6.85-17.11]). Accordingly, several agents provided higher ACR20 rates than placebo, with infliximab yielding the most favorable results (RR=3.02 [1.67-4.55]). Overall, rates of SAE and AE were higher for several but not all biologic agents versus placebo, with golimumab being associated with the most favorable results for SAE (RR=0.40 [0.11-1.41]), and abatacept for AE (RR=1.00 [0.79-1.22]). Conclusions: Efficacy and safety of biologic agents for psoriasis differ, and clinicians should bear in mind these features to maximize safety and efficacy in the individual patient.

Consensus statement of the Spanish Society of Rheumatology on the management of biologic therapies in psoriatic arthritis

ObjectiveDue to the amount and quality variability regarding the use of biologic therapy (BT) in psoriatic arthritis (PsA) patients, the Spanish Society of Rheumatology (SER) has promoted the generation of recommendations based on the best evidence available. These recommendations should serve as reference to rheumatologists and those involved in the treatment of patients with PsA, who are using, or about to use BT. MethodsRecommendations were developed following a nominal group methodology and based on systematic reviews. The level of evidence and degree of recommendation was classified according to the model proposed by the Center for Evidence Based Medicine at Oxford. The level of agreement was established through Delphi technique. ResultsWe have produced recommendations for the use of TB currently available for PsA in our country. These recommendations include disease assessment, treatment objectives, therapeutic scheme and switching. ConclusionsWe present an update on the SER recommendations for the use of BT in patients with PsA.

Analysis of 4-year Dutch reimbursement application data of biological therapies for psoriatic arthritis

To get the approval for reimbursement of biological therapies for PsA, patients need to fulfil specific criteria in many countries. The aim of this study was to evaluate the 4-year Dutch reimbursement application data, including the diagnostic, disease activity and response criteria that were applied for treatment of PsA with biologics. All initial and follow-up applications for approval of treatment with biologics were included for investigation. Data were analysed descriptively with regard to application characteristics, patient characteristics and response to therapy. In the period studied, 3723 application forms of 1991 patients were received. This concerned 2118 initial treatment applications and 1605 follow-up applications. Of all initial treatment applications, 2003 (94.6%) were approved. The major part of all applications concerned requests for etanercept (59.1%), followed by adalimumab (38.2%). Patients were suffering from polyarthritis in most cases (63.1%). MTX was used by nearly all patients, but only 55.8% had used the required dosage of 25 mg/week. Approximately 79.4% of all patients met the response criteria after 3 months of treatment. The mean number of affected joints declined from 7.7 at first application to 1.4 at follow-up. The initial visual analogue scale (VAS) score indicated by patients decreased from 71.2 to 24.1 at follow-up. The VAS score indicated by physicians decreased from 66.0 to 18.4. Biologics are expensive, but highly effective in the treatment of PsA. Careful compilation of treatment and reimbursement criteria is important for patients as well as for physicians and health insurance companies.

Anti-TNF alpha dans le traitement du rhumatisme psoriasique

Psoriatic arthritis is an inflammatory and possibly destructive form of arthritis. As in rheumatoid arthritis and ankylosing spondylitis, the use of biological therapy in psoriatic arthritis is a therapeutic revolution: both articular and cutaneous efficacy have been shown, and some improvement is visible on radiography. The benefit-risk ratio will improve when we learn to identify more accurately the patients likely to benefit from these treatments.

Consensus exercise on domains in psoriatic arthritis

Recent studies with biological therapy in psoriatic arthritis (PsA) have highlighted the need for validated and widely accepted assessment tools and outcome measures for this disease. A Delphi process was...