Mean Drug Survival Research Articles

Safety and effectiveness of disease-modifying therapies after switching from natalizumab

Introduction: One strategy to mitigate progressive multifocal leukoencephalopathy (PML) risk is to switch to other highly effective disease-modifying therapies (DMTs). However, the optimal switch DMT following natalizumab (NTZ) discontinuation is yet to be determined. Objective: The objective of the study is to determine the most effective and tolerable DMTs to switch to following NTZ discontinuation due to John Cunningham virus (JCV) antibody positivity. Methods: This is a multicenter observational cohort study that included all stable relapsing-remitting multiple sclerosis (MS) patients who were treated with NTZ for at least 6 months before switching therapy due to JCV antibody positivity. Results: Of 321 patients, 255 switched from NTZ to rituximab/ocrelizumab, 52 to fingolimod, and 14 to alemtuzumab, with higher annualized relapse rate (ARR) in fingolimod switchers (0.193) compared with rituximab/ocrelizumab or alemtuzumab (0.028 and 0.032, respectively). Fingolimod switchers also had increased disability progression (p = 0.014) and a higher proportion developed magnetic resonance imaging (MRI) lesions compared with rituximab/ocrelizumab (62.9% vs. 13.0%, p < 0.001, and 66.6% vs. 24.0%, p < 0.001, respectively). Mean drug survival favored rituximab/ocrelizumab or alemtuzumab over fingolimod (p < 0.001). Conclusion: Our study shows superior effectiveness of rituximab/ocrelizumab and alemtuzumab compared with fingolimod in stable patients switching from NTZ due to JC virus antibody positivity.

Predictive value of the systemic immune inflammation index and systemic inflammatory response index on omalizumab drug survival in chronic spontaneous urticaria

Abstract Background Omalizumab is recommended as adjunctive therapy for antihistamine-refractory chronic spontaneous urticaria (CSU). However, its long-term effectiveness is understudied. The systemic immune-inflammation index (SII) and the systemic inflammatory response index (SIRI) have shown prognostic value in cancer, strokes, and other diseases. Objectives This study aimed to evaluate the long-term effectiveness of omalizumab in CSU patients while investigating potential associations of SII and SIRI with the drug survival of omalizumab. Methods A retrospective study was conducted using patient data from the electronic hospital database, including patients with CSU treated with omalizumab between January 2018 and May 2021. Drug survival curves were visualized using Kaplan-Meier survival analysis. and Cox regression was utilized to assess potential associations. Results A total of 109 CSU treated with omalizumab at the University Hospital of Zurich were included. The mean drug survival was 13.6 ± 10.9 months. The mean SII and SIRI were 796.1 ± 961.3 and 2.1 ± 3.1, respectively. The multivariate model revealed that SIRI (p = 0.098) was a more robust predictor of omalizumab’s drug survival than SII (p = 0.367), while concurrent autoimmune disease or baseline immunoglobulin E (IgE) levels showed no significant impact. Conclusion This study suggests the potential utility of SIRI as a superior predictive indicator for omalizumab’s drug survival in CSU patients compared to SII. Concomitant autoimmune disease or baseline IgE levels did not significantly affect the drug’s effectiveness.

P80 Real-world evidence of the effectiveness of secukinumab in patients with psoriasis with and without scalp involvement from the British Association of Dermatologists Biologics and Immunomodulators Register

Abstract Secukinumab is a fully human anti-interleukin-17A monoclonal antibody approved for the treatment of moderate-to-severe plaque psoriasis in adults, adolescents and children aged ≥ 6 years. The British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) is an ongoing prospective observational registry that collects long-term data from patients receiving biologics for psoriasis in the UK and the Republic of Ireland. We report the clinical effectiveness, drug survival and patient-reported outcomes of secukinumab treatment in patients from BADBIR with psoriasis with and without scalp involvement. Patients aged ≥ 18 years who had one or more follow-up visit(s) after enrolment in BADBIR and were receiving secukinumab according to label (300 mg weekly loading dose for 5 weeks, followed by monthly dosing) were included (data cutoff 31 August 2021). Baseline Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) scores recorded between 4 and 8 months and 10 and 14 months of secukinumab initiation were used as 6- and 12-month time points, respectively. Overall mean drug survival was calculated at 12, 24 and 36 months for patients with and without scalp involvement. Outcomes of interest were the proportion of patients with PASI scores of ≤ 2 and DLQI scores of 0/1. Drug survival up to 36 months (Kaplan–Meier method) was defined as the duration between the date of first exposure to secukinumab and date of stopping secukinumab or the end of the study censoring period. The analysis included 1298 patients with psoriasis with scalp (n = 883; 68.0%) and without scalp (n = 415; 32.0%) involvement. The mean duration of follow-up was 2.9 and 2.8 years in patients with and without scalp involvement, respectively. The majority were male (60.4% and 61.5%), mean age was 45.9 and 49.5 years, mean age at disease onset was 24.7 and 26.8 years, mean baseline PASI scores were 15.2 and 14.5, and mean baseline DLQI scores were 17.4 and 17.0 in patients with and without scalp involvement, respectively. Overall, the drug survival rates at 12, 24 and 36 months were 86%, 73% and 63% and 86%, 77% and 69% in patients with psoriasis with and without scalp involvement, respectively. At 6 and 12 months of treatment, 73.9% and 70.4% and 72.1% and 68.4% of patients with and without scalp involvement, respectively, achieved PASI scores ≤ 2. At 6 and 12 months of treatment, 56.9% and 59.2% and 52.0% and 55.4% of patients with and without scalp involvement, respectively, achieved DLQI scores of 0/1. This analysis of real-world data from BADBIR shows that treatment with secukinumab resulted in high drug survival and sustained and consistent improvements in PASI and DLQI in most patients with psoriasis with and without scalp involvement.

32428 Secukinumab is effective and safe in the treatment of recalcitrant palmar-plantar psoriasis and palmar-plantar pustular psoriasis in a daily practice setting

Background: Palmar-plantar psoriasis (PP) and palmar-plantar pustular psoriasis (PPPP) are frequently recalcitrant to treatment. Currently we have limited information from guidelines for their management. Objective: To study drug effectiveness, safety and persistence as well as quality of life in patients with PP and PPPP treated with secukinumab (SEK) in real clinical practice. Methods: Retrospective, observational, noncontrolled, multicenter cohort, long-term study of patients with moderate-to-severe PP and PPPP (ppIGA/pppIGA score of ≥3) treated with SEK under daily practice conditions, conducted between January 2014 and July 2020. Results: Seventy-two patients (55 PP, 17 PPPP) were included. A 56.36% and 52.94% of PP and PPPP patients, respectively, achieved ppIGA/pppIGA response scores of 0 or 1 or a reduction of at least 2 points on the ppIGA/pppIGA scale from baseline in the 24-month follow-up. We found statistically significant differences in the ppIGA at 12 months between naïve subjects and patients with prior biologic therapy, with greater effectiveness in naïve patients. The mean drug survival for PP and PPP patients were 12.7 and 13.4 months, respectively. Safety profile was good. Limitations: Those derived from the retrospective and multicenter nature of the study with patients treated in daily clinical practice. Conclusions and relevance: SEK is a safe, fast and effective treatment alternative for some patients with PP and PPPP refractory to previous systemic or biologic treatments.

Use of Apremilast® in the psoriasis treatment: a real-life multicenter Italian experience.

Apremilast® (Amgen, Thousand Oaks, CA, USA) is the first small molecule approved for the treatment of moderate-to-severe psoriasis in adult patients; however, real-life data are still limited. We investigated the effectiveness and safety of this drug in a multicenter real-world setting. We retrospectively reviewed data from all psoriatic patients who received at least one dose of Apremilast® (Amgen) and collected demographic data and medical history at baseline and periodically for 36 months. A total of 111 patients entered in the study. The mean drug survival duration was 21.8±10.6 months; however, it was significantly shorter when comorbidities were ≥3 and if biologic drugs were previously administered. ΔPASI90 was achieved in 29% of patients and ΔPASI50 in 68% at T4; the rate of ΔPASI improvement increased progressively at T12, T24, T36 in patients who continued to receive Apremilast® (Amgen). At the end of the study 50 patients discontinued the treatment because of adverse events (19.8%), primary failure (19%) or secondary failure (6.3%). Apremilast® (Amgen) proved to be an effective, safe, and manageable drug, showing effectiveness also in difficult-to-treat patients with psoriasis, with a favorable tolerability profile and a potentially valid weight loss effect. We believe that treating patients with few comorbidities who are naive to biological therapy may result in higher response rates and longer mean drug survival.

Long-term use of spironolactone for acne in women: A case series of 403 patients

Thereare limited data regarding the long-term outcomes of spironolactone use for women with acne and its effect on truncal acne. To comprehensively describe outcomes of patients treated with spironolactone in routine clinical practice, including long-term outcomes. We performed a retrospective case series of 403 adult women treated for acne with spironolactone at an academic medical center between 2008 and 2019. Rates of objective, as assessed by Comprehensive Acne Severity Scale scores, and subjective acne clearance were evaluated, as well as rates of treatment discontinuation, dosage changes, and drug survival. Logistic regression was used to assess for association between incidence of menstrual adverse effects and combined oral contraceptive use. As evaluated by Comprehensive Acne Severity Scale scores, at the first follow-up, 75.5%, 84.0%, and 80.2% of patients with available data had reduction or complete clearance of acne on the face, chest, and back, respectively. The mean drug survival was 470.7days. Menstrual adverse effects were less common among those using combined oral contraception (odds ratio, 0.23; 95% confidence interval, 0.11-0.50). This study was conducted at a single academic medical center. Spironolactone improves clinical outcomes and is well tolerated for many adult women with acne using it for an extended duration.

Comorbidities burden and previous exposure to biological agents may predict drug survival of apremilast for psoriasis in a real‐world setting

Apremilast is the first small molecule approved for the treatment of moderate to severe psoriasis and psoriatic arthritis in adult patients. To evaluate survival, efficacy and safety of apremilast in patients with moderate to severe psoriasis and investigate possible associations between apremilast survival and clinical parameters in a real-world setting. In this retrospective study, a total of 71 patients who started on apremilast treatment between March 2017 and December 2019 were identified and included in the study: 40 (56.3%) males and 31 (43.7%) females, with a mean age of 55.6 ± 13.8 years and a mean Body Mass Index of 28.4 ± 6.9 kg/m2 . At the end of the study 49.3% of patients remained on apremilast with mean treatment duration 67.2 ± 41.1 weeks (range 4-132). Overall, mean drug survival duration was 78.51 weeks (95% CI: 65.8-91.2 weeks). Mean drug survival was shorter when comorbidities burden was higher (P = .012) and with previous exposure of biological agents (P = .001). Previous exposure to biological agents (HR:3.86, 95% CI: 1.35-11.04, P = .012) and comorbidities burden (HR: 2.27, 95% CI: 1.25-4.12, P = .007) were independent predictors of drug discontinuation adjusting for important clinical parameters. In this real-world setting, apremilast presented better survival rates when introduced early on the onset of moderate psoriasis, especially in biologic naïve patients with less comorbidities. More prospective and larger studies are required to determine clinical parameters affecting drug survival.

Omalizumab for cholinergic urticaria: 6 months prospective study and systematic review of the literature.

To examine the effectiveness of omalizumab on disease activity and quality of life in patients with cholinergic urticaria (CholU). Further, a systematic review of the literature was performed to identify all studies of use of omalizumab in CholU. A total of 23 patients (63.9%) were refractory to updosed non-sedating antihistamines and initiated omalizumab in the observation period. Among these, an improvement of 10.8 UAS7 points (4.6-17.0), P = .002, was seen at 6 months follow up. DLQI and disease bother score VAS also improved significantly from before initiating treatment with omalizumab to follow-up; 7.0 points (3.6-10.3), P < .001 and 3.1 points (1.5-4.8), P = .001, respectively. The overall mean drug survival time for omalizumab (discontinued due to any cause) was 30.6 months (22.2-39.0). A total of five patients (21.7%) reported suspected side effects (headache, muscle pain, fatigue and injection site reactions) during treatment with omalizumab until 6 months follow-up. The systematic literature review identified 58 additional antihistamine refractory patients with CholU treated with omalizumab. The available studies reported that omalizumab is effective in patients with CholU and improves their disease-related quality of life. Omalizumab is safe, reduces disease activity and improves disease-related quality of life in patients with CholU.

EP43 Biologic retention in psoriatic arthritis: a real world study

Abstract Background Biologics have led to a sea change in the management of psoriatic arthritis (PsA) with unprecedented improvement in the signs, symptoms and radiographic damage, resulting in improvement in functionality and quality of life. However longitudinal data for their retention and tolerability is sparse. Our objective was to evaluate real-world biologic therapy duration and reasons for discontinuing treatment. Methods We conducted a retrospective analysis of our PsA electronic register from 1994 up to and including April 2019 at our university teaching hospital. We had access to full patient records including details on co-morbidities, drugs and disease management. Results 335 patients were identified with PsA. 58% were female with mean age 46 yr (13-81). 113 (33.7%) patients had been treated with a biologic with 105 (93%) continuing at the time of analysis. 60 individuals were prescribed combination therapy with DMARDs. Mean age was 43.3 (13-81) with 56% women. The biologics sample was ethnically diverse including 80% White Caucasian patients, 17% Asian and others (3%). Significant co-morbidities included cardiovascular disease (18.6%) and diabetes (4.4%). Eight different biologics were in use with adalimumab being the most prescribed (67%). 35 (30.9%) patients had stopped biologics at some point with 76 episodes of cessation. 6% of our sample had discontinued two or more biologic treatments. The mean duration before biologic therapy was discontinued was 18.2 months (8 days to 9.5 years), which was almost twice as long as the average period before discontinuing a DMARD (9.9 months). Main reasons for stopping treatment included 23% each due to GI symptoms, neurological causes, cutaneous symptoms and other side effects. The remaining 8% reported fatigue as the reason for stopping therapy. Conclusion To our knowledge this is the first dedicated retrospective review of a large real world PsA cohort comparing drug survival and tolerability of biologics against DMARDs. Biologic therapies are well tolerated in psoriatic arthritis. There is no significant difference amongst various modes of action. Over a quarter of the patients discontinue the drug owing to intolerance with mean drug survival of 18 months. In contrast nearly two-thirds were intolerant of DMARDs and stopped within ten months. Thus both the rate and duration of biologic retention is significantly better than conventional DMARDs. This has significant economic impact as NICE guidelines require an adequate trial of two DMARDs for six months prior to advanced therapy. However, this approach is unlikely to be cost effective as the disease progresses whilst patients struggle with DMARDs prescription and thus delay biologics which are more likely to be tolerated and retained longer. Hence there is an urgent need to review NICE guidelines to allow earlier employment of biologics in the treatment paradigm with significant benefits to both patients and the health economy. Disclosures: I. Jawad: None. M.K. Nisar: None.

Drug survival in patients with psoriasis is associated with the availability of biologic medications.

Drug survival rates in patients with psoriasis had been described extensively. Different survival rates of TNF-α inhibitors (TNFIs), ustekinumab and secukinumab were reported. To investigate drug survival rates of TNFIs, ustekinumab and secukinumab, with particular emphasis on the difference between ustekinumab and secukinumab. Survival analysis was performed in patients with moderate-to-severe psoriasis who received adalimumab, infliximab, etanercept, ustekinumab and secukinumab treatment in 2002-2018, using the Clalit Health Services database. Stratified analysis was performed according to biologic treatment lines. Multivariate analysis was performed adjusting for demographic variables, calendar year, metabolic syndrome, psoriatic arthritis, biologic treatment line, biologic naivety, co-administration of oral treatments and previous oral systemic treatment exposure. Among 1459 patients treated with 3070 biologic medication courses, ustekinumab had a significantly higher crude survival as compared with TNFIs and secukinumab. The mean drug survival of ustekinumab, adalimumab, etanercept, infliximab and secukinumab was 43.5 (CI: 39.7-47.2), 38.2 (CI: 34.8-41), 33.9 (CI: 30.8-37.1), 28.2 (CI: 22.5-33.8) and 17.1 (CI: 15.6-18.6) months, respectively, with significant statistical differences for all comparisons (P<0.001). The differences between ustekinumab and secukinumab were not significant following adjustment to factors that included treatment line (hazard rate 1.16, CI: 0.93-1.43). Different drug survival rates between ustekinumab and secukinumab are determined by the treatment line and calendar year, reflecting the availability of biologic medications, and not only by the biologic attributes of each medication.

Ixekizumab Survival in Heavily Pretreated Patients with Psoriasis: A Two-year Single-centre Retrospective Study.

The long-term effect of intra-anti-interleukin-17-class switch on drug survival is unclear. The aim of this study was to evaluate the efficacy and long-term survival of ixekizumab in bio-experienced psoriatic patients with and without previous exposure to anti-interleukin-17 treatment. Retrospective search of a tertiary medical centre database for 2017 to 2019 yielded 73 patients treated with ixekizumab: 50 previously exposed to secukinumab and 23 anti-interleukin-17-naïve. Median baseline Psoriasis Area Severity Index (PASI) was 23.0. Median number of received biologics was 4. Mean drug survival was 16.4 and 16.8 months in the anti-interleukin-17-exposed and naïve groups, respectively (p = 0.878). There was no between-group difference in proportion of patients achieving ≥ 75 PASI response. At study end, 25 anti-interleukin-17-exposed patients (50.0%) and 17 anti-interleukin-17-naïve patients (73.9%) were still on ixekizumab. The use of multiple previous biologic treatments was associated with substantially reduced ixekizumab survival. In conclusion, previous anti-interleukin-17-exposure was associated with an initially favourable response and did not further reduce ixekizumab survival.

Drug maintenance of a second tumor necrosis factor alpha inhibitor in spondyloarthritis patients: A real-life multicenter study.

Five TNF inhibitor (TNFi) agents are marketed for spondyloarthritis (SpA): 1 soluble receptor (SR) and 4 monoclonal antibodies (mAbs). From 15% to 30% of patients stop the first TNFi in the first 2 years, but we lack recommendations on the choice of the second TNFi. The aim here was to assess drug survival of a second TNFi in SpA and its determinants. This was a multicenter observational study of SpA patients who started a first TNFi in 2013 and 2014 and were followed to 2018. For the first and second TNFi, we retrospectively collected data on initiation and discontinuation dates, type of TNFi, and reasons for withdrawal. Kaplan-Meier plots and log-rank tests were used to compare drug survival. Factors associated with drug survival of the second TNFi were analyzed by univariate Cox regression analyses. We included 244 patients. During a follow-up of 7,838 patient-months, 101 (41%) received 1 TNFi, and 143 (59%) switched to a second TNFi. Mean drug intake duration was significantly greater with the first than second TNFi: 21.7 (SD 19.6) and 15.4 (SD 13.6) months (P<0.001). When switching to another mAb or from an SR to an mAb (or the reverse), mean drug survival did not differ: 14.4 (SD 12.7) and 16 (SD 14.1) months (P=0.35). Factors associated with retaining the second TNFi were male sex (P=0.054) and age<41 years at SpA diagnosis (P=0.022). On multivariable analysis, only age<41 years at diagnosis remained independently associated with maintenance of the second TNFi. In SpA patients, drug survival is significantly longer with the first than second TNFi. Male sex and age<41 years at diagnosis were associated with retaining the second TNFi.

Economic Factors as Major Determinants of Ustekinumab Drug Survival of Patients with Chronic Plaque Psoriasis in Korea.

BackgroundDrug survival, defined as the time until discontinuation, is a parameter reflecting real-world therapeutic effectiveness. Few studies have examined the influence of economic factors on the drug survival of biologic agents for psoriasis, particularly in Asian countries.ObjectiveTo determine the drug survival for ustekinumab in real-life settings and investigate the factors affecting drug survival for psoriasis patients in Korea.MethodsWe evaluated 98 psoriasis patients who were treated with ustekinumab at a single center. We analyzed the efficacy and drug survival of ustekinumab. Cox proportional hazard analysis and competing risk regression analysis were performed to reveal the factors affecting the drug survival of ustekinumab.ResultsThe overall mean drug survival was 1,596 days (95% confidence interval [CI], 904~2,288). Among the 39 cessations of ustekinumab treatment, 9 (23.1%) patients discontinued treatment after experiencing satisfactory results. Multivariate Cox proportional hazard analysis revealed that paying on patients' own expense was the major predictor for the discontinuation of ustekinumab (hazard ratio [HR], 9.696; 95% CI, 4.088~22.998). Competing risk regression analysis modeling of discontinuation because of factors other than satisfaction of an event also revealed that ustekinumab treatment at the patient's expense (HR, 4.138; 95% CI, 1.684~10.168) was a predictor of discontinuation rather than satisfaction.ConclusionThe results of our study revealed that the cost of biologics treatment affects the drug survival of ustekinumab and suggested that economic factors affect the drug survival of ustekinumab treatment in Korea.

THU0363 Efficacy and Tolerability of Anti-TNF Therapies in Patients with Non-Radiographic Axial Spondyloarthritis: An Observational Cohort Study from Southern Sweden

BackgroundTreatment recommendations for patients with axial spondyloarthritis (SpA) [1], including non-radiographic axial SpA (nr-axSpA), presents anti-TNF therapies as an option in patients who fail NSAIDs, however at present clinical data...

The use of in-vitro drug resistance levels as a predictor of outcome in soft tissue sarcoma

20510 Background: We have assayed in-vitro drug resistance and immunohistochemical staining for drug resistance markers (MDR-1, MRP) in patients with metastatic soft tissue sarcoma patients. We looked at resistance to Cisplatin, Doxorubicin, and Ifosphamide, prior to beginning chemotherapy. The aim of this study was to investigate the validity of in-vitro drug resistance testing as a predictor of outcome. Methods: Viable tumor samples obtained at time of recurrence or metastasis from 13 patients with metastatic soft tissue sarcoma were tested by a semiquantitative 12 hour tritiated-thymidine uptake cell-proliferation assay (EDR test, Oncotech Inc., Tusin, California) for resistance to the chemotherapy drugs cisplatin, doxorubicin, and ifosphamide. The mean drug resistance level for these three drugs was plotted against survival in months, both from time of metastasis and time of initiation of chemotherapy. Mean resistance was also correlated with positive staining for either MDR-1 or MRP. Results: There was no relationship found between the mean drug resistance and survival, either from time of metastasis (correlation coefficient -0.0596) or time of initiation of chemotherapy (correlation coefficient - 0.1864). There was no correlation between mean drug resistance and; 1) presence of MDR-1 staining (correlation coefficient -0.1269), 2) presence of MRP staining (correlation coefficient -0.2175), 3) presence of either staining for MDR-1 or MRP (correlation coefficient -0.2636). Conclusions: 1) In-vitro drug resistance is not predictive of outcome in patients with soft tissue sarcoma. 2) There is no correlation between the mean drug resistance and positive staining for either MDR-1 or MRP. No significant financial relationships to disclose.