Drug Survival Of Adalimumab Research Articles

P668 Dashboard-guided anti-TNF induction as an effective proactive strategy in Inflammatory Bowel Disease's treatment

Abstract Background Infliximab (IFX) and Adalimumab (ADA) are effective treatments for managing Inflammatory Bowel Disease (IBD) but treatment failure is common. Therapeutic drug monitoring (TDM) of trough serum drug concentrations (C Trough) has been used to optimize treatment induction, mitigate immunogenicity, and ensure appropriate drug exposure. HLA DQA1*05 genotype variants have been identified as predictors of immunogenicity. This study aimed to investigate the impact of dashboard-guided optimized induction dosing strategy on clinical and pharmacokinetics outcomes of anti-TNF, with the goal of analysing the HLA DQA1*05 effect. Methods We conducted a retrospective single-centre cohort analysis of IBD patients, Crohn’s disease (CD) and Ulcerative Colitis (UC), who initiated treatment with IFX or ADA between January 2020 and March 2023, using a pharmacokinetic dashboard-guided induction, protocolized with the Pharmacy Department. C Trough measurements were taken at week 2, 6 and 14, first drug intervention based on the model was in week 4. Targeted C Trough levels during induction were set at 10-15 mcg/mL for ADA and > 17 mcg/mL for IFX. Primary objective was to assess clinical remission (CR). Secondary outcomes included treatment failure (TF) and endoscopic remission (ER). We performed a descriptive analysis and generated Kaplan Meier curves to assess drug survival Results We enrolled 147 patients, 92 having CD (74 treated with ADA and 18 with IFX) and 55 having UC (36 treated with ADA and 19 CU with IFX). HLA DQA1*05 genotype variant was present in 44,14% of patients. Combined treatment with thiopurine was used in 45,58% and 11,54% had been previously received biologic treatment. After 24 weeks, 91,83% (135/147) of patients achieved CR and 65,81% (77/117) at week 56. ER was observed in 59,84% (76/127) after a year. Anti-TNF drug survival probability was 85% after a year, meanwhile ADA drug survival in UC patients was 75%. A 77,7% of patients were prescribed an accelerated dose in the first year, which was associated with improved drug durability. Only a patient out of 147 developed antibodies to ADA. The HLA DQA1*05 variant was not a statistically significant predictor of adverse treatment or pharmacokinetic outcomes. Conclusion Optimizing anti-TNF induction with a Dashboard-guide dosing strategy proves to be a valuable approach to enhance clinical remission and durability rates in IBD patients. The role of HLADQA1*05 variant in immunogenicity appears to be mitigated by the model.

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

Drug Survival of Adalimumab, Secukinumab, and Ustekinumab in Psoriasis as Determined by Either Dose Escalation or Drug Discontinuation during the First 3 Years of Treatment – a Nationwide Cohort Study

The real-world efficacy of biologics may be insufficiently assessed through common drug survival studies. The objective was thus to examine the real-world performance of biologics in the treatment of psoriasis using the composite endpoint of either discontinuation or off-label dose escalation. Using a prospective nationwide registry (DERMBIO, 2007-2019), we included patients with psoriasis treated with adalimumab, secukinumab, and/or ustekinumab, which have all been used as first-line therapy during the inclusion period. The primary endpoint was a composite of either off-label dose escalation or discontinuation of treatment, whereas the secondary outcomes were dose escalation and discontinuation, respectively. Kaplan-Meier curves were used for the presentation of unadjusted drug survival curves. Cox-regression models were used for risk assessment. In 4,313 treatment series (38.8% women, mean age 46.0 years, and 58.3% bio-naivety), we found that the risk of the composite endpoint was lower for secukinumab when compared with ustekinumab (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.59-0.76), but higher for adalimumab (HR 1.15, 95% CI 1.05-1.26). However, the risk of discontinuation was higher for secukinumab (HR 1.24, 95% CI 1.08-1.42) and adalimumab (HR 2.01, 95% CI 1.82-2.22). For bio-naive patients treated with secukinumab, the risk of discontinuation was comparable to that of ustekinumab (HR 0.95, 95% CI 0.61-1.49).

Employing Adalimumab in Treatment of Moderate‐to‐Severe Hidradenitis Suppurativa: Real‐Life Multicenter Data from the Czech Republic

Adalimumab is the only approved biologic treatment for moderate‐to‐severe hidradenitis suppurativa, nonetheless, long‐term data from real‐life setting are still limited. The objective of this observational multicenter study was to evaluate the effectiveness, safety, and drug survival of adalimumab in patients with hidradenitis suppurativa included in the BIOREP registry. A total of 299 patients who initiated adalimumab therapy for hidradenitis suppurativa from 2011 to November 2021 were included. The Dermatology‐Life‐Quality‐Index (DLQI), pain scale, the number of abscesses, inflammatory nodules and draining tunnels, and International Hidradenitis Suppurativa Severity Score System (IHS4) were recorded in the 0th, 3rd, and 6th months; then every 6 months during the ongoing adalimumab treatment. Studied patients underwent treatment for up to 48 months, with the average duration of treatment lasting 2.3 years. The mean age of the patients was 44.9 years, 79% were smokers or ex‐smokers, 54.8% were obese, and 26.4% were overweight, the mean BMI was 30.8. The mean time from diagnosis to initiation adalimumab therapy was 9.1 years. The number of patients with severe IHS4 dropped from the initial 249 (83.3%) to 65 (30.1%) after 12 months and this trend was maintained up to the 48th month. A decreasing number of inflammatory lesions were rapid and sustained and correlated to the improvement of patients’ quality of life, the mean DLQI score dropped from 17.6 to 8.5 after 3 months and to 5, 7 after 48 months. No unexpected risk signals were observed. Our long‐term study demonstrates the effectiveness and safety of adalimumab in a real‐life setting.

Adalimumab and infliximab survival in patients with hidradenitis suppurativa: a daily practice cohort study.

SummaryBackgroundBiologics are often required for the treatment of hidradenitis suppurativa (HS). However, data on the drug survival of biologics in daily practice are currently lacking.ObjectivesTo assess the drug survival of antitumour necrosis factor biologics in a daily practice cohort of patients with HS and to identify predictors for drug survival.MethodsA retrospective multicentre study was performed in two academic dermatology centres in the Netherlands. Adult patients with HS using biologics between 2008 and 2020 were included. Drug survival was analysed with Kaplan–Meier survival curves and predictors of survival with univariate Cox regression analysis.ResultsThe overall drug survival of adalimumab (n = 104) at 12 and 24 months was 56·3% and 30·5%, respectively, which was predominantly determined by infectiveness. Older age (P = 0·02) and longer disease duration (P < 0·01) were associated with longer survival time. For infliximab (n = 44), overall drug survival was 58·3% and 48·6% at 12 and 24 months, respectively, and was predominantly determined by infectiveness and side‐effects. Surgery during treatment was associated with a longer survival time (P = 0·01).ConclusionsSurvival rates were comparable for adalimumab and infliximab at 12 months, and were mainly determined by ineffectiveness. Age, disease duration (adalimumab) and surgery (infliximab) are predictors for longer survival.

Drug survival of adalimumab, ustekinumab and secukinumab in patients with psoriasis: a prospective cohort study from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR).

Real-world biologic drug survival is an important proxy measure for effectiveness. Predictors of drug survival may help patients with psoriasis choose between biologic therapies. (i) To assess the relative drug survival of adalimumab, ustekinumab and secukinumab in patients with psoriasis. (ii) To investigate predictors of biologic drug survival. A prospective cohort study was performed in the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) between November 2007 and August 2019. We performed survival analysis and fitted a flexible parametric survival model for biologic discontinuation due to ineffectiveness. In total 9652 patients were included: 5543 starting on adalimumab (57·4%), 991 on secukinumab (10·3%) and 3118 on ustekinumab (32·3%). The overall drug survivals of adalimumab, secukinumab and ustekinumab in year 1 were 0·78 [95% confidence interval (CI) 0·77-0·79], 0·88 (95% CI 0·86-0·91) and 0·88 (95% CI 0·87-0·89), respectively. The adjusted hazard ratios (adjHRs) for discontinuation of adalimumab and secukinumab compared with ustekinumab were 2·11 (95% CI 1·76-2·54) and 0·67 (95% CI 0·40-1·11), respectively. The presence of psoriatic arthritis predicted for survival in the adalimumab and secukinumab cohorts (adjHR 0·67, 95% CI 0·51-0·88 and 0·70, 95% CI 0·40-1·24, respectively), but for discontinuation in the ustekinumab cohort (adjHR 1·42, 95% CI 1·12-1·81). Previous exposure to biologic therapies predicted for discontinuation in the ustekinumab and secukinumab cohorts (adjHR 1·54, 95% CI 1·26-1·89 and 1·49, 95% CI 0·91-2·45, respectively) and for survival in the adalimumab cohort (adjHR 0·71, 95% CI 0·55-0·92). Secukinumab and ustekinumab have similar sustained drug survival, while adalimumab has a lower drug survival in patients with psoriasis. Psoriatic arthritis and previous biologic experience were predictors with differential effects between the biologic therapies. What is already known about this topic? There is conflicting evidence over the real-world drug survival of secukinumab in patients with psoriasis. Data from registries to date suggest that secukinumab has a lower drug survival than that reported from clinical trials. What does this study add? This study found that secukinumab and ustekinumab had similar sustained drug survival in the real world, while the drug survival of adalimumab was lower, suggesting that the real-world drug survival of secukinumab is higher than previously reported. We found that psoriatic arthritis and previous biologic experience had differential effects on drug discontinuation in the three biologic cohorts. These predictors may help patients and clinicians choose the most appropriate biologic therapy.

Optimizing adalimumab treatment in psoriasis with concomitant methotrexate (OPTIMAP): study protocol for a pragmatic, single-blinded, investigator-initiated randomized controlled trial

BackgroundThe introduction of anti-tumor necrosis factor medications has revolutionized the treatment of psoriasis with achievement of treatment goals (Psoriasis Area and Severity Index score 75, remission) that are not usually met with conventional systemics. Nevertheless, some patients continue to experience persistent disease activity or treatment failure over time. Strategies to optimize treatment outcomes include the use of concomitant methotrexate, which has demonstrated beneficial effects on pharmacokinetics and treatment efficacy in psoriasis and other inflammatory diseases.MethodsThis is an investigator-initiated, multicenter randomized controlled trial (RCT) designed to compare the combination treatment of adalimumab and methotrexate with adalimumab monotherapy in patients with psoriasis. The primary outcome is adalimumab drug survival at week 49. Other outcomes include improvement in disease severity and quality of life, tolerability, and safety. Moreover, anti-adalimumab antibodies and adalimumab serum concentrations will be measured and correlations between genotypes and clinical outcomes will be assessed. Patient recruitment started in March 2014. Up to now, 36 patients have been randomized. Many more patients have been (pre)screened. A total of 93 patients is desired to meet an adequate sample size. In our experience, the main limitation for recruitment is prior adalimumab therapy and intolerability or toxicity for methotrexate in the past.DiscussionOPTIMAP is the first RCT to examine combination therapy with adalimumab and methotrexate in a psoriasis population. With data derived from this study we expect to provide valuable clinical data on long-term treatment outcomes. These data will be supported by assessment of the impact of concomitant methotrexate on adalimumab pharmacokinetics. Furthermore, the influence of several single nucleotide polymorphisms on adalimumab response will be analyzed in order to support the development of a more personalized approach for this targeted therapy.Trial registrationNTR4499. Registered on 7 April 2014.

Sex Is Associated with Adalimumab Side Effects and Drug Survival in Patients with Crohn's Disease.

Adalimumab (ADA) is an effective treatment for Crohn's disease (CD). In rheumatology, sex differences concerning the response to ADA therapy have been described. However, such differences have not yet been reported for patients with CD. As such, the aim of this study was to compare ADA treatment outcomes in male and female patients with CD. A clinical cohort was formed of consecutive patients with CD starting ADA in a single tertiary center between March 2006 and February 2011. The cohort was followed up to August 2015. Clinical outcomes were primary nonresponse, secondary nonresponse, and drug survival (ongoing ADA use). Reasons for stopping ADA were recorded. Kaplan-Meier analysis and Cox regression were used to assess drug survival. The cohort consisted of 107 female and 81 male patients. Median follow-up was 6.0 years (range 0.3-9.2). Drug survival was higher in male than female patients (48.1% versus 30.8%, P = 0.016). Side effects were reported more often by female patients (81.3% versus 64.2%, P = 0.008), and female patients ceased ADA more often due to side effects (35.4% versus 18.4%, P = 0.017). In survival analysis, female sex was associated with higher cessation rates (P = 0.006). Cox regression also identified female sex (P = 0.020), along with higher baseline CD Activity Index (P = 0.003), as predictors of ADA cessation. Female sex is negatively associated with ADA drug survival. Female patients report more side effects and cease ADA because of side effects more often. A more personalized and sex-specific approach seems warranted to increase drug survival in female patients.

Drug survival of adalimumab in patients with rheumatoid arthritis over 10years in the real-world settings: high rate remission together with normal function ability.

The purpose of the study was to estimate the clinical profile of naïve biological patients with rheumatoid arthritis (RA) starting adalimumab through 3-year calendar periods and their clinical outcomes such as drug survival and global clinical disease control (GCDC). RA patients starting adalimumab as first biological drug between 2003 and 2012 were subdivided in 3-year calendar periods. Survival on therapy was estimated using the Kaplan-Meier analysis. One and 2-year clinical response was assessed by calculating percentage of patients attaining GCDC (28-joint Disease Activity Score (DAS28)≤2.6+Health Assessment Questionnaire (HAQ)≤0.5), low disease activity (DAS28≤3.2), remission (DAS28≤2.6) and good European League Against Rheumatism (EULAR) response. Multivariate regression models were used to assess baseline predictors of drug discontinuation or achievement of clinical remission. We recruited 1695 RA patients. Overall drug persistence at 3years was 40.6%, while the global rate of nonswitching patients was 54.7%. Compared to 2003-2005, initiators in more recent years had a significantly lower 3-year crude drug retention rate (log rank, p<0.0001) and a significantly higher rate of switching to alternative biologics (log rank, p<0.0001). No difference in adverse events or effectiveness rate among the calendar periods was found. A substantial proportion of patients (up to 27%) achieved GCDC at 2years, regardless of the calendar period. In real-life setting, RA patients starting adalimumab in more recent years had a higher rate of drug discontinuation not related to ineffectiveness or side effects but to switching, probably due to a wider availability of biologics. A meaningful proportion of patients attained GCDC without any difference across calendar periods.

Adalimumab drug survival in patients with psoriasis, Crohn's disease, and rheumatoid arthritis: Relevant differences using the same treatment

Adalimumab drug survival in patients with psoriasis, Crohn's disease, and rheumatoid arthritis: Relevant differences using the same treatment

Drug survival for adalimumab in a long-term daily practice cohort of patients with psoriasis

Drug survival for adalimumab in a long-term daily practice cohort of patients with psoriasis

'Happy' drug survival of adalimumab, etanercept and ustekinumab in psoriasis in daily practice care: results from the BioCAPTURE network.

Drug survival is a marker for treatment success. To date, no analyses relating dermatological quality-of-life measures to drug survival have been published. (i) To describe 1-year drug survival for adalimumab, etanercept and ustekinumab in a daily practice psoriasis cohort, and (ii) to introduce the concept of 'happy' drug survival, defined as Dermatology Life Quality Index (DLQI)≤5 combined with being 'on drug' at a specific time point. Data were extracted from a prospective registry. Drug survival was analysed using Kaplan-Meier estimates. 'Happy' drug survival was calculated, with data split into 'happy' (DLQI ≤5) vs. 'unhappy' (DLQI >5) at baseline and months 3, 6, 9 and 12. 249 treatment episodes were included (101 adalimumab, 82 etanercept, 66 ustekinumab). The 1-year drug survival rates for ustekinumab, adalimumab and etanercept were 85%, 74% and 68%, respectively. Ustekinumab showed a better confounder-corrected drug survival vs. etanercept [hazard ratio (HR) 3·8, P=0·02] and a trend towards better survival vs. adalimumab (HR 2·3, P=0·1). At baseline, the majority (n=115, 73%) was considered 'unhappy' and a minority 'happy' (n=42, 27%) (ratio 'happy':'unhappy' was 1 : 2.7). The percentage of treatment episodes with 'happy' on-drug patients increased to 79% after 1 year. Ustekinumab showed a better overall drug survival than etanercept, and a trend towards a better overall drug survival than adalimumab. After 1 year, patients reported to be 'happy' in 79% of episodes and 'unhappy' in 21%. We introduced the new concept of 'happy' drug survival because the proportion of on-drug patients with good quality of life is an important indicator for treatment success.