Longer Drug Survival Research Articles

Real-World Data on Brodalumab Treatment in Patients with Moderate-to-Severe Plaque Psoriasis: An Observational Study from the Czech Republic BIOREP Registry.

The aim of this observational, multicenter study was to assess the real-world use of brodalumab for the treatment of moderate-to-severe plaque psoriasis in patients in the Czech Republic, using data from the BIOREP registry. The study included 273 patients aged≥18years with moderate-to-severe psoriasis who received brodalumab. Endpoints were drug survival (time from treatment initiation to discontinuation), effectiveness [Psoriasis Area and Severity Index (PASI)], and health-related quality-of-life [Dermatology Life Quality Index (DLQI)]. Predicted drug survival probability was 92.4% [95% confidence interval (CI): 89.1, 95.7%] at 6months and 84.2% (95% CI 79.5, 89.1%) at 12months; this was maintained at 24months [80.4% (95% CI 74.5, 86.8%)]. Younger age, higher body mass index, and no previous biologic treatment were significantly associated with longer drug survival. Absolute PASI≤3 after 3months was achieved by 89.8% of patients; 92.4%, 77.8%, and 59.1% reached PASI 75, PASI 90, and PASI 100, respectively. After 12months, 96.5% of 141 patients had an absolute PASI≤3. The proportion of patients achieving DLQI 0/1 was 87.3% at 12months. This study demonstrated high and sustained drug survival with high rates of skin clearance and improved quality of life in patients with relatively severe disease treated with brodalumab. Improvements were observed as early as 3months post-treatment initiation and were sustained for up to 24months in a real-life setting.

Drug survival of biologics in psoriasis: An Australian multicentre retrospective study.

Drug survival, which refers to the time from treatment initiation to discontinuation, provides a surrogate measure of the effectiveness of a biologic in a real-world setting (J Invest Dermatol, 2015, 135, 1). The aim of this study was to determine the drug survival of biologics that are currently available in Australia. We also analysed the treatment efficacy of these biologics and reasons for discontinuation. Retrospective data from outpatient Dermatology biologic clinics in Westmead Hospital and Royal Prince Alfred Hospital (Sydney, Australia) from April 2006 to December 2020 were collected. Kaplan-Meier analysis was used to calculate drug survival. A total of 306 patients who underwent 566 treatment courses were analysed. Guselkumab was observed to have the longest drug survival, with cumulative drug survival rates of 94.2% ± 4.0 at 1- and 5-years. This was followed by ixekizumab which had a 1-year survival rate of 87.2% ± 4.5 and 5-year survival rate of 59.4% ± 9.5. Ixekizumab and guselkumab were also noted to have superior treatment efficacy compared with other biologics, with PASI-75 rates of 94.9% and 93.8%, respectively. The most common reasons for treatment discontinuation were a lack of initial efficacy to treatment and a loss of efficacy over time despite an initial response, respectively. To our knowledge, this is the first Australian study to report on outcomes of multiple new biologics that are currently in use for the treatment of chronic plaque psoriasis. Overall, this study provides insight into patterns of care from a local experience that may help guide the management of moderate-to-severe psoriasis.

Type 1/like Calr Mutation in Momelotinib-Treated Patients with Myelofibrosis Is the Most Prominent Predictor of Drug Survival and Longevity without Transplant

Background: Non-transplant treatment options in myelofibrosis MF are palliative in scope and include Janus kinase 2 (JAK2) inhibitors (JAKi). FDA-approved JAKi for the treatment of MF include ruxolitinib, fedratinib, and pacritinib. A fourth JAKi, momelotinib, is currently under review. We have previously reported long-term survival data on momelotinib and drug survival that was significantly longer, retrospectively compared to ruxolitinib ( AJH. 2022;97:E433). In the current study, we focused on molecular predictors of drug survival (i.e., drug retention) and longevity without allogeneic hematopoietic stem cell transplant AHSCT (transplant-censored survival). Methods : The current study included data from Mayo Clinic patients who participated in a phase-1/2 core study of momelotinib (NCT00935987). Study design, drug doses and schedule, and additional details on treatment effect and side effects have previously been published. Drug survival was calculated from time of initiation of momelotinib to time of treatment discontinuation. Survival analysis required censoring of patients at time of AHSCT. Conventional statistical methods were applied using JMP Pro 16.0.0 software (SAS Institute, Cary, NC, USA). Results : 79 JAKi-naïve patients with MF were considered: median age 67 years; males 54%; PMF 65%, post-PV MF 20%, post-ET MF 15%; JAK2 71%, type 1/like CALR ( CALR-1) 14%, CALR-2 3%, MPL 8%, triple-negative 5%. Risk category according to DIPSS was high/intermediate in 80% of the patients and unfavorable karyotype in 29%. Non-driver mutation information was available in a subset of patients and included ASXL1 22% and SRSF2 18%. Median time from diagnosis to study entry was 25.2 months; patients were enrolled between November 2009 and March 2011 with follow-up information updated through July 2023; during this period, 68 (86%) deaths, 13 (16%) leukemic transformations, and 7 (9%) AHSCTs were recorded. Median follow-up for alive patients was 12.5 years (range 11.3-13.1). Anemia response rate was 48% and spleen 47%. Median treatment duration was 25 months (range 0.1-157); the proportion of patients remaining on active therapy was 68% at 1 year, 30% at 3 years, 16% at 5 years, and 7% at 10 years (Figure 1a). At the time of this writing, 5 (6.3%) patients were still receiving momelotinib therapy with treatment durations of 152 to 157 months. In univariate analysis, molecular predictors of drug survival included CALR-1 (p=0.006) but not ASXL1 (p=0.6) or SRSF2 (p=0.3) mutation, or unfavorable karyotype (p=0.08). The 3-, 5-, and 10-year drug survival rates for CALR-1-mutated patients were 64%, 40%, and 18%, respectively, and for CALR-1 wild-type 25%, 11%, and 4% (p=0.01, Figure 1b). CALR-1 independent association with longer drug survival was also appreciated for younger age (p<0.01) and absence of baseline transfusion dependency at time of study entry (p=0.02); all three risk factors remained significant during multivariable analysis with HR (95% CI) rates of 0.4 (0.2-0.87) for CALR-1, 0.5 (0.3-0.89) for age <63 years, and 0.6 (0.3-0.9) for absence of transfusion-dependency. Spleen response (p<0.01) but not anemia response (p=0.23) was also associated with longer drug survival; in multivariable analysis all 4 risk factors retained significance. Multivariable analysis of genetic variables for transplant-censored survival identified absence of CALR-1 (HR 3.5, 95% CI 1.2-10.5; p=0.03) and presence of high molecular risk (HMR; ASXL1/ SRSF2) mutations (HR 2.3, 95% CI 1.1-4.6; p=02) to independently predict inferior survival. Among 11 patients with CALR-1 mutation, median transplant-censored survival was 125 months with 10-year survival rate of 60% (Figure 1c); by contrast, the corresponding figures were 37 months and 12%, in the 68 patients not harboring CALR-1 mutation (Figure 1c). In multivariable analysis, absence of CALR-1 (HR 2.9, 95% CI 1.02-8.1), age ≥63 years (HR 3.0, 95% CI 1.5-6.0), and absence of spleen response (HR 2.6, 95% CI 1.5-4.5) were identified as being most significant in predicting inferior transplant-censored survival. Conclusions : CALR-1 mutation is the most important risk factor for both drug survival and longevity without AHSCT, in momelotinib-treated patients with MF. Such information might help identify MF patients who might benefit from treatment with momelotinib and in whom AHSCT might be deferred or not.

Improving the Accuracy of Biologic Drug Survival Data: The Increasing Prevalence of Off-Label Dosing Must Be Considered when Reporting Drug Effectiveness and Safety

Improving the Accuracy of Biologic Drug Survival Data: The Increasing Prevalence of Off-Label Dosing Must Be Considered when Reporting Drug Effectiveness and Safety

P720 Drug survival of first-line biologics in inflammatory bowel disease: large single-centre experience from UR-CARE

Abstract Background The expanding therapeutic armamentarium for inflammatory bowel disease (IBD) has led to uncertainty about the optimal first-line biological therapy for a given patient. Given the paucity of dedicated head-to-head trials, treatment decisions can be supported by network meta-analyses or real-world data. Our aim was to assess the drug survival of first-line biologics by drug class (anti-tumour necrosis factor [TNF] agents, anti-integrin, anti-interleukin [IL]-12/23) and identify potential predictors for prolonged drug survival in our cohort of IBD patients, supported by the United Registries for Clinical Assessment and Research (UR-CARE). Methods We prospectively included all adult patients with IBD treated with biological drugs and at least one follow-up visit between October 2021 and August 2022 at our tertiary referral centre. Patient data were collected retrospectively from records and included demographics, disease characteristics and drug survival. Data were collected in UR-CARE with data lock on August 1, 2022. Cox regression was used to assess the association of patient and disease characteristics with drug survival of first-line biologic drugs by drug class. Results We included 1047 adult patients with IBD (644 Crohn’s disease [CD], 403 ulcerative colitis [UC]) (Table 1). Among TNF antagonists, adalimumab was most frequently used in CD (280/644, 43.5%; infliximab: 241/644, 37.4%), infliximab was most frequently used in UC (169/403, 41.9%; adalimumab: 55/403, 13.6%; golimumab: 52/403, 12.9%). Unadjusted median drug survival of the first-line biologic did not differ by medication class in CD, but was significantly longer for vedolizumab than for anti-TNF agents in UC (hazard ratio [HR] for discontinuation 0.585, 95% confidence interval [CI] 0.41–0.84; P = 0.003) (Table 2). Disease duration and extent were not associated with drug survival. In CD, isolated ileal disease was associated with longer drug survival (HR 0.83, 95% CI 0.70–0.99; P = 0.04). Findings for both CD and UC were consistent in a sensitivity analysis of patients (CD 228, UC 202) started on biologics after January 1, 2019 when all three drug classes could be prescribed first line without limitations. Conclusion In our cohort of 1047 patients with IBD, the drug survival of first-line biologics was comparable regardless of drug class in CD. In UC, first-line vedolizumab was associated with longer drug survival. Disease location and duration did not impact drug survival.

Adalimumab or etanercept as first line biologic therapy in enthesitis related arthritis (ERA) - a drug-survival single centre study spanning 10 years

ObjectivesTo analyse and compare drug-survival of adalimumab and etanercept (and their biosimilars) in biologic-naïve patients with ERA (Enthesitis-Related Arthritis). MethodsIn this retrospective observational study, conventional statistics and machine-learning were applied to compare drug-survival (adalimumab, etanercept and their biosimilars initiated: 2009–2019) in ERA and identify determinants. The primary outcome was discontinuation of treatment due to primary- or secondary-failure and adverse drug-reactions. ResultsDuring the observation period, 99 of 188 patients with ERA on first-line TNF inhibitors (etanercept-n=108, adalimumab-n=80) discontinued their treatment (median survival-time 3.9years, 95%CI 2.6-4.9years). Adalimumab was associated with longer drug-survival compared to etanercept especially after an initial positive response, with the median time to treatment discontinuation 4.9years (95% CI 3.9–5.7) for adalimumab, compared to 2years (95%CI 1.4–4.0) for etanercept (HR of treatment-discontinuation-0.49, 95%CI 0.32–-0.75, p=0.001). Adjusted by propensity-score, adalimumab-methotrexate combination was associated with longer drug survival, compared to adalimumab-monotherapy (HR-0.41, 95%CI 0.20–0.85), etanercept-monotherapy (HR-0.28, 95%CI 0.15–0.53), and etanercept-methotrexate combination (HR-0.39, 95%CI 0.21–0.73). The presence of HLA-B27 was associated with longer drug-survival (HR-0.50, 95%CI 0.29–0.87) following an initial positive response. Higher-CRP at baseline was associated with higher rate of primary-failure (HR-1.68, 95%CI 1.08–2.62). Axial-ERA (sacroiliitis±spinal-involvement) was associated with poorer drug-survival for both primary- and secondary-failure (overall HR-2.03, 95%CI 1.22–3.40). Adjusted by propensity-score, shorter drug-survival was observed in patients with baseline-CRP≥12.15 mg/L, but only in the context of axial-ERA, not in peripheral-ERA (no sacroiliitis/spinal-involvement) (HR-2.28, 95%CI 1.13–-3.64). ConclusionFollowing an initial positive primary response, continuing methotrexate with adalimumab was associated with the longest drug-survival compared to adalimumab-monotherapy or etanercept-based regimens. Axial-ERA was associated with a poorer drug-survival. A CRP >12.15 in patients with axial-ERA was associated with a higher rate of primary-failure. Further prospective studies are required to confirm these findings.

Factors associated with drug survival on first biologic therapy in patients with rheumatoid arthritis: a population-based cohort study.

Lack of sufficient head-to-head trials comparing biologic disease-modifying antirheumatic drugs (bDMARDs) in rheumatoid arthritis (RA), makes the choice of the first bDMARD a matter of rheumatologist's preference. Longer drug survival on the first bDMARD usually correlates with early remission. We aimed to identify factors associated with longer drug survival. We conducted a population-based retrospective longitudinal cohort study. We identified RA patients using the relevant International Classification of Disease 9th codes. "True" RA patients were defined as patients fulfilling, additionally, at least one of the following: receiving conventional DMARDs (cDMARDs), being positive for rheumatoid factor or anti-cyclic citrullinated peptide, or being diagnosed by a rheumatologist. We compared drug survival times and identified factors associated with longer drug survival. We identified 4268 true RA patients between the years of 2000-2017. 820 patients (19.2%) received at least one bDMARD. The most commonly prescribed bDMARDs were etanercept (352, 42.9%), adalimumab (143, 17.4%), infliximab (142, 17.3%) and tocilizumab (58, 7.1%). Infliximab was associated with the longest drug survival (47.1months ± 46.3) while golimumab was associated with the shortest drug survival (14.9months ± 15.1). Male gender [hazard ratio (HR) = 0.76, 95% confidence interval (CI), 0.63-0.86, p = 0.001], concurrent conventional DMARDs use (HR = 0.79, 95% CI 0.68 - 0.98, p = .031) and initiating bDMARD therapy in earlier calendric years (HR = 1.12, 95% CI 1.10 -1.18, p = 0.0001) were associated with longer drug survival. Male gender, concomitant cDMARDs and initiating biologic therapy at earlier calendric years are associated with longer drug survival.

Response to Biologics During the First Six Months of Therapy in Biologic-naïve Patients with Psoriasis Predicts Risk of Disease Flares: A Danish Nationwide Study.

Early response to treatment with biologics might be important for the stability of psoriasis and long-term outcome. The aim of this study was therefore to assess whether risk of flares and drug survival are associated with disease activity in the first 6 months of treatment of psoriasis with biologics. Biologic-naïve patients from the Danish nationwide registry, DERMBIO, were grouped based on absolute Psoriasis Area and Severity Index (PASI) during the first 6 months of treatment, as: PASI = 0, PASI > 0–≤2, PASI > 2–≤ 4, and PASI > 4. Among 1,684 patients, 746 achieved PASI= 0, 485 PASI > 0–≤2, 246 PASI > 2–≤4, and 207 PASI > 4. Longer flare-free period and drug survival were observed for patients with lower PASI in the first 6 months of treatment (adjusted hazard ratios for flares (95% confidence interval) with PASI= 0 as reference: PASI > 0–≤2 (1.35 (1.11–1.72]), PASI > 2–≤ 4 (2.32 [1.80–2.99]), and PASI > 4 (2.38 [1.80–3.15])). In conclusion, a low PASI in the first 6 months of treatment with biologics in biologic-naïve patients with psoriasis was associated with a more stable disease course, lower risk of flares, and longer drug survival.

Predictors of drug survival of biologic therapies in psoriasis patients

Introduction We aimed to investigate the clinical, immunological, and genetic factors affecting the response to anti-TNFα (tumor necrosis factor-α) and interleukin-12/23 therapies and drug survivals. Methods A total of 180 patients were divided into two groups: 89 patients who used at least two biologic agents, with the initial biologic agent used less than 12 months (group A), and 91 biologic-naive patients who have been receiving a single biologic agent for more than 12 months (group B). ELISA (enzyme-linked immunosorbent assay) was used to analyze anti-drug antibodies (ADAs) in blood samples. Clinical data of the patients were retrospectively analyzed. HLA-SSO (sequence-specific oligonucleotide) Typing Kits were used for HLA-C typing. IBM SPSS v.21 was used for statistical analysis. Results: Infliximab had the longest drug survival as the first biologic agent in group A (p = .015). Etanercept had the lowest ADA count compared to the other anti-TNF agents (p = .001). HLA-Cw6 negativity, late-onset psoriasis, smoking and alcohol use were determined to be risk factors for treatment failure in group A. HLA-Cw6 was found to be associated with type I psoriasis (p = .000). Conclusions Although our study is retrospective of a relatively low number of patients, this is a preliminary study focusing on two different patient populations based on therapy response.

Efficacy and Safety of Biologics for Psoriasis and Psoriatic Arthritis and Their Impact on Comorbidities: A Literature Review

Psoriasis is a chronic inflammatory skin disease characterized by scaly indurated erythema. It impairs patients’ quality of life enormously. It has been recognized not only as a skin disease but as a systemic disease, since it also causes arthritis (psoriatic arthritis) and mental disorders. Furthermore, an association with cardiovascular events is indicated. With the advent of biologics, treatment of psoriasis dramatically changed due to its high efficacy and tolerable safety. A variety of biologic agents are available for the treatment of psoriasis nowadays. However, characteristics such as rapidity of onset, long-term efficacy, safety profile, and effects on comorbidities are different. Better understanding of those characteristic leads to the right choice for individual patients, resulting in higher persistence, longer drug survival, higher patient satisfaction, and minimizing the disease impact of psoriasis. In this paper, we focus on the efficacy and safety profile of biologics in psoriasis patients, including plaque psoriasis and psoriatic arthritis. In addition, we discuss the impact of biologics on comorbidities caused by psoriasis.

Drug survival of conventional systemic and biologic therapies for moderate-to-severe psoriasis in clinical practice in Spain: prospective results from the SAHARA study

Background: A better understanding of determinants for drug survival of antipsoriatic agents may guide dermatologists in the right therapeutic choice.Objectives: To describe 2-year drug survival of conventional and biologic antipsoriatic treatments.Methods: SAHARA was a prospective study in patients with moderate-to-severe psoriasis who initiated a conventional or biologic drug. Kaplan-Meier analysis estimated the drug survival and Cox regression the predictors of treatment persistence at two years.Results: A total of 552 patients were included (conventional group n = 181, biologic group n = 371). After a median treatment duration of 21.4 months, more than 50% of patients remained on methotrexate, etanercept, and ustekinumab whereas the median exposition time to cyclosporine, acitretin, and adalimumab was 11.8, 10.6, and 25.5 months, respectively. There were 178 discontinuations for all causes, mainly in patients who initiated cyclosporine (58.3%), acitretin (52.8%), and adalimumab (46%), and less frequently with ustekinumab (14%). The main reason for discontinuing biologics was lack of efficacy (70%), especially for etanercept (76%).Conclusion: Biologics have a superior drug survival rate than conventional therapies. Ustekinumab is the biologic with the longest drug survival, only affected by the gradual loss of efficacy assumed for biological therapies.

Long-term etanercept survival in patients with psoriatic arthritis: a multicenter retrospective analysis in daily clinical practice in Spain.

Although several randomized clinical trials and observational studies have evaluated the effectiveness, safety and drug survival of etanercept (ETN) in the treatment of psoriatic arthritis (PsA), long-term data regarding these aspects are currently scarce. For this reason, we sought to investigate the long-term survival and safety of ETN in PsA patients in 4 tertiary care Spanish hospitals over a 13-year observation period (from 2004 to 2017). The records of 85 PsA patients were reviewed. ETN showed an excellent survival profile, with rates of treatment discontinuation at 1, 3, 5 and 10years of 15, 37, 46 and 59%, respectively. In our cohort, a trend toward longer drug survival in patients with shorter disease duration and those who were treated with ETN as their first biologic agent was observed. On the other hand, combination therapy with conventional disease-modifying antirheumatic drugs did not provide greater improvement on the long-term drug survival. Only 12% of the patients reported adverse events (AEs) during therapy, being most of them of mild to moderate intensity, and in only 7% AEs led to drug discontinuation. To the best of our knowledge, the present study shows the largest follow-up period of ETN-treated population analyzed in a real-life setting, and these results demonstrate the positive safety profile and long-term effectiveness of this biologic agent in the management of PsA patients.

P635 Real-world treatment persistence and associated costs with biologic therapy in patients with inflammatory bowel disease (IBD): Results of a retrospective cohort analysis of 1,149 patients treated in Germany

Data on biologic treatment (Tx) persistence and switching in German IBD patients are sparse. The main objectives of this interim analysis of a retrospective claims database (7.5 Mio. insured, covering out- and inpatient care) were to describe rates of biologic Tx switching and discontinuation for anti-TNFα (adalimumab, golimumab, infliximab) and vedolizumab (VDZ) IBD patients and to report associated drug costs. Adult patients with a confirmed diagnosis of Crohn’s disease or ulcerative colitis (63% of 37%), initiating Tx with an anti-TNFα or VDZ between 1 July 2015 and 30 June 2016 and follow-up for 12 months (or death within 12 months) were included. Observation started with the first prescription in this period. First observed Tx discontinuation (prescription gap >90 days) and switching to another biologic were compared between anti-TNFα and VDZ patients, both unadjusted and adjusted (Cox regression). Drug costs, based on pharmacy retail prices, were reported per observed patient month for periods of continuous index Tx. 1149 out of 51,222 IBD patients started anti-TNFα or VDZ within the inclusion period. Of these, 582 patients were followed up for 12 months or until death (n = 4) in this interim analysis (476 anti-TNFα: mean age, 37.2 years, 53.9% female, 78.7% bio-naïve; 107 VDZ: mean age, 40.5 years, 55.1% female, 21.5% bio-naïve). During follow-up, 20.6% vs. 16.8% of anti-TNFα vs. VDZ patients (p = 0.227) switched to another biologic agent; 19.8% vs. 15.0% (p = 0.154) discontinued index Tx, and 59.4% vs. 67.6% (five patients censored; p = 0.060) continued Tx. VDZ Tx was associated with longer drug survival (mean 309 days) than anti-TNFα Tx (286 days; p = 0.028). In the multivariable Cox regression, female gender was associated with earlier Tx discontinuation and switch (HR = 1.490; 95% CI: 1.139–1.949), whereas VDZ Tx was associated with later discontinuation and switch (HR = 0.692; 95% confidence interval (CI): 0.480–0.998); prior biologic Tx and comorbidity were not significant. Drug costs per patient month were €2,561.66 for anti-TNFα and €2,314.74 for VDZ. 12-month treatment continuation of anti-TNFα vs. VDZ patients in a German claims database. In contrast to previous observational evidence, less than two-thirds of IBD patients continued Tx with a biologic agent after 12 months. There is a tendency towards a longer drug survival in VDZ patients, with comparable drug costs. Analysis of the full dataset including 1,149 patients will provide more detail, especially for subgroups (UC vs. CD and bio-naïve vs. bio-experienced).

Effectiveness of Tumor Necrosis Factor Inhibitors in Combination with Various csDMARD in the Treatment of Rheumatoid Arthritis: Data from the DREAM Registry.

To analyze and compare the effectiveness and drug survival in patients with rheumatoid arthritis, as measured by 28-joint Disease Activity Score (DAS28) and Health Assessment Questionnaire-Disability Index (HAQ-DI), of tumor necrosis factor inhibitor (TNFi) monotherapy, TNFi + leflunomide (LEF), TNFi + sulfasalazine (SSZ), TNFi + other conventional synthetic disease-modifying antirheumatic drugs (csDMARD), and TNFi + methotrexate (MTX) therapy, in daily practice. Data were collected from the DREAM registry. Patients beginning their first TNFi treatment were included in the study: TNFi monotherapy (n = 320), TNFi + SSZ (n = 103), TNFi + LEF (n = 80), TNFi + other csDMARD (n = 99), TNFi + MTX alone (n = 919), TNFi + MTX + other csDMARD (n = 412). Treatment effectiveness was analyzed using DAS28 and HAQ-DI with linear mixed models and the TNFi drug survival was analyzed using Kaplan-Meier curves and Cox regression. All analyses have been corrected for confounders. The patients who received TNFi + MTX had significantly better DAS28 and HAQ-DI values over time (both p < 0.001) and longer TNFi drug survival than TNFi monotherapy (p < 0.001). TNFi + SSZ and TNFi + other csDMARD had significantly better DAS28 values over time (p = 0.001) and longer drug survival (p = 0.001) versus TNFi monotherapy. TNFi + LEF was not significantly better compared to monotherapy. Adding other csDMARD to the TNFi + MTX combination provided no added value. Preferably, TNFi should be prescribed together with MTX. If this is not possible, we advise the use of other csDMARD.

Predictors of adalimumab drug survival in psoriasis differ by reason for discontinuation: long-term results from the Bio-CAPTURE registry.

Drug survival is an indicator for treatment success; insight in predictors associated with drug survival is important. To analyse the long-term drug survival for adalimumab in patients with psoriasis treated in daily practice and (II) to identify predictors of prolonged drug survival for adalimumab split for different reasons of discontinuation. Data were extracted from a prospective psoriasis cohort and analysed using Kaplan-Meier survival curves split for reasons of discontinuation. Baseline predictors associated with longer drug survival were identified using multivariate Cox-regression analysis. One hundred and sixteen patients were included with a total of 208 patient-years. Overall drug survival was 76% after 1year and 52% after 4.5years. In patients who stopped due to ineffectiveness, longer drug survival was associated with the absence of specific comorbidities (P=0.03). In patients who stopped due to side-effects, longer drug survival was associated with male gender (P=0.02). Predictors of adalimumab drug survival in psoriasis differ by reason for discontinuation. Strong, specific predictors can lead to patient-tailored treatment.

Drug survival of fumaric acid esters for psoriasis: a retrospective study

Fumaric acid esters (FAEs) have been used for over 30 years in the management of psoriasis. To determine drug survival of FAEs in patients with psoriasis, treatment-limiting adverse drug events and the range of effective drug doses. A retrospective, single-centre study assessing all patients commenced on FAEs between October 2003 and July 2012. Demographic data, length of treatment, reasons for discontinuation of FAEs, side-effects and range of doses were recorded. Two hundred and forty-nine patients [160 (64%) male] were included. The mean age at which FAEs were commenced was 44·5 years (range 17-82 years). The mean length of treatment was 28 months (range 1 week to 106 months). In patients who were commenced on FAEs ≥ 4 years before inclusion in this study, the 4-year drug survival was 60% (64/107). FAEs were discontinued in 146/249 patients (59%); this was due to lack of efficacy in 59/146 (40%) and gastrointestinal upset in 39/146 (27%). A very low dose of FAEs (< 240 mg daily) was successful in maintaining control of psoriasis in 26 (10%) patients. The mean treatment duration of these patients was 64 months (range 32-106 months). Fumaric acid esters have a 4-year drug survival rate of 60%, which compares favourably with reported 4-year survival rates of 40% for etanercept and adalimumab and 70% for infliximab. Longer drug survival is more likely in the significant subgroup of patients in whom a very low dose of FAEs is sufficient to control disease. The reasons for this are unclear.

Treatment response, drug survival, and predictors thereof in 764 patients with psoriatic arthritis treated with anti–tumor necrosis factor α therapy: Results from the nationwide Danish DANBIO registry

To investigate disease activity, treatment response, and drug survival, and predictors thereof, among Danish patients with psoriatic arthritis (PsA) receiving their first treatment series with a tumor necrosis factor α (TNFα) inhibitor. Patients with PsA were identified from a prospective nationwide rheumatologic database, the Danish biologics registry DANBIO, using data registered from 2000-2009. Information was obtained on the patients' clinical response to anti-TNFα treatment (defined as achievement of the American College of Rheumatology 20% [ACR20], ACR50, and ACR70 improvement criteria or a European League Against Rheumatism [EULAR] good response at least once during the first 6 months of treatment) and duration and rate of drug adherence (referred to as drug survival), as well as predictors thereof. Of 764 patients with PsA, 320 received adalimumab, 260 infliximab, and 184 etanercept. Median drug survival was 2.9 years, and 1-year and 2-year drug survival rates were 70% and 57%, respectively. Clinical parameters that showed improvement over 6 months were the C-reactive protein (CRP) level, Health Assessment Questionnaire score, and 28-joint Disease Activity Score. Male sex, CRP level >10 mg/liter, concomitant methotrexate use, and low patient health visual analog scale score at baseline were associated with longer drug survival. Improvement was achieved by 59%, 45%, 24%, and 54% of patients according to the ACR20, ACR50, ACR70 response criteria and EULAR good response, respectively. A CRP level >10 mg/liter was predictive of the improvement responses (odds ratio [OR] 2.6 for ACR20, OR 3.0 for ACR50, OR 3.6 for ACR70, and OR 2.2 for EULAR good response). In these patients with PsA treated with their first TNFα inhibitor in clinical practice, high drug adherence and responder rates were observed. Moreover, increased levels of CRP at baseline were associated with both good treatment responses and continued treatment, which may be of clinical value in selecting the patients most likely to benefit from treatment with TNFα inhibitors.

Predictors of treatment response and drug continuation in 842 patients with ankylosing spondylitis treated with anti-tumour necrosis factor: results from 8 years' surveillance in the Danish nationwide DANBIO registry

ObjectivesTo use prospectively registered data from the Danish nationwide rheumatological database (DANBIO) to describe disease activity, clinical response, treatment duration and predictors of drug survival (ie, number of days individual...