Burden of disease among patients with prevalent Crohn's disease: results from a large German sickness fund.

PURPOSE: The aim of this study was to investigate the burden of disease among a real-world cohort of patients with prevalent Crohn's disease (CD) in Germany. METHODS: We conducted a retrospective cohort analysis using administrative claims data from the German AOK PLUS health insurance fund. Continuously insured patients with a CD diagnosis between 01 October 2014 and 31 December 2018 were selected and followed for at least 12 months or longer until death or end of data availability on 31 December 2019. Medication use (biologics, immunosuppressants (IMS), steroids, 5-aminosalicylic acid) was assessed sequentially in the follow-up period. Among patients with no IMS or biologics (advanced therapy), we investigated indicators of active disease and corticosteroid use. RESULTS: Overall, 9284 prevalent CD patients were identified. Within the study period, 14.7% of CD patients were treated with biologics and 11.6% received IMS. Approximately 47% of all prevalent CD patients had mild disease, defined as no advanced therapy and signs of disease activity. Of 6836 (73.6%) patients who did not receive advanced therapy in the follow-up period, 36.3% showed signs of active disease; 40.1% used corticosteroids (including oral budesonide), with 9.9% exhibiting steroid dependency (≥ 1 prescription every 3 months for at least 12 months) in the available follow-up. CONCLUSIONS: This study suggests that there remains a large burden of disease among patients who do not receive IMS or biologics in the real world in Germany. A revision of treatment algorithms of patients in this setting according to the latest guidelines may improve patient outcomes.

Guselkumab Treatment Outcomes and Persistence in a Nationwide Real-world Cohort of Patients with Plaque Psoriasis.

Guselkumab treatment outcomes and persistence were assessed in a real-world cohort of Finnish patients with difficult-to-treat plaque psoriasis over a median follow-up of 1 year. Data on 181 patients who initiated guselkumab at the 15 study centres were collected retrospectively from the patient charts. Prior exposure to biologic therapies was common, with 56% and 35% having used at least 1 and 2 biologics, respectively. Median guselkumab treatment duration was 11 months with 21 patients (12%) discontinuing treatment during follow-up. Of 85 patients with a follow-up duration of at least 1 year, 73 (86%) were still on guselkumab at 1 year. Significant improvements during follow-up were seen in the absolute Psoriasis Area and Severity Index (PASI) scores with 32 patients (80%) having absolute PASI ≤ 2 after a 9-14-month treatment. Guselkumab treatment was effective and treatment persistence was high in the nationwide Finnish real-life setting.

Ustekinumab for Crohn's disease: a nationwide real-life cohort study from Finland (FINUSTE).

Background: Ustekinumab (UST), a human anti-IL12/23p40 monoclonal antibody, has been approved for treatment of Crohn's Disease (CD) since the end of 2016. This nationwide noninterventional, retrospective chart review explored real-life data in patients receiving UST to provide guidance in UST treatment in the era of increasing prevalence of CD. Methods: The study assessed UST treatment patterns such as dosing frequency, concomitant medication and persistence in 48 CD patients commencing UST therapy in 12 Finnish hospitals during 2017. Clinical remission and response rates were explored using a modified Harvey-Bradshaw index (mHBI) and endoscopic response via the simple endoscopic score for Crohn's disease (SES-CD) as proportions of patients at week 16 and at the end of follow-up. Results: Forty patients (83%) continued UST-treatment at the end of follow-up. At week 16, clinical response and endoscopic healing was observed, where data were available; mHBI decreased from 9 to 3 (p = .0001) and SES-CD from 12 to 3 (p = .009). Clinical benefit was achieved by 83% (19/23) at week 16 and by 76% (16/21) at the end of follow-up. The proportion of patients using corticosteroids decreased from 48% to 25% at week 16 and to 13% at the end of the follow-up. Conclusion: UST showed to be effective and persistent, inducing short-term clinical benefit and endoscopic response in this real-life nationwide study of CD patients. Significant corticosteroid tapering in patients with highly treatment refractory and long-standing CD was observed.

Pregnancy Outcomes Reported During the 13-Year TREAT Registry: A Descriptive Report.

OBJECTIVES: We described pregnancy outcomes in Crohn's disease (CD) patients enrolled in the TREAT Registry who received infliximab before, or during pregnancy and those not treated with infliximab or any biologic agent. METHODS: In the TREAT Registry (1999-2012), pregnancy outcomes were analyzed from maternal and paternal patients exposed to infliximab ≤365 days (gestational exposure), >365 days (pre-gestational exposure) of pregnancy outcome or without infliximab exposure (non-biologic exposed). "Healthy infants" were defined as those with no congenital abnormalities, neonatal complications (e.g., jaundice, prematurity, heart murmur, cortical vision/fine motor delay, cardiac failure, hemophilia, or torticollis), prolonged hospitalization, or those who received no special treatment. Disease activity and concomitant medications were also evaluated. RESULTS: Overall, 92.3% (324/351) of pregnancies had known outcomes. The majority of both maternal pregnancies (92.6, 91.2, and 87.8%) and partner outcomes (92.7, 93.8, and 91.7%) resulted in live births of healthy infants across gestational, pre-gestational, and non-biologic exposure groups, respectively. Among these, rates of neonatal complications were low for both maternal (6.2, 7.0, and 8.5%), and partner outcomes (4.9, 0, and 0%) in gestational, pre-gestational, and non-biologic exposure groups, respectively. Among maternal pregnancies, numerically higher rates of spontaneous abortions were observed for the gestational exposure group than for the pre-gestational or non-biologic exposed groups. CONCLUSIONS: The clinical condition of infants born to women with gestational infliximab exposure was similar to those without exposure. Although a lower live birth rate was reported among infliximab-exposed women, these patients had more severe CD and were more likely to have been exposed to immunosuppressives.

Impacts of X-linked Retinitis Pigmentosa and Patient Pathways in European Countries: Results from the Cross-sectional EXPLORE XLRP-1 Physician Survey.

INTRODUCTION: X-linked retinitis pigmentosa (XLRP) is a rare, incurable, vision-threatening, genetic disease. In this study, we aimed to reveal the real-world burden of this disease from the viewpoint of retina specialists and geneticists involved directly in XLRP care and to identify unique insights that may not otherwise be available through typical clinical studies or health economic research. METHODS: In this exploratory, cross-sectional study (EXPLORE XLRP-1), retina specialists (n = 20) and geneticists (n = 5) in France, Germany, Italy, Spain, and the UK provided anonymized insights on their experiences managing patients with XLRP (n = 80) via an online survey and 60-min telephone interview. RESULTS: Survey respondents reported that patient independence decreased over time, where 37% of patients were considered "completely autonomous" at diagnosis versus 23% at the last consultation. At their last visit, 45% of patients were active in the workforce; 67% (12/18) of "completely autonomous" patients had active working status compared with 13% (1/8) of "completely dependent" patients. The average time from onset of symptoms to diagnosis was 4 years and varied among countries. In 78% of patients, XLRP was confirmed by genetic testing, the rate of which varied among countries (range, 50-94%), taking up to 6 months to receive results. Specialists identified unmet needs in XLRP management including more standardized assessments of quality of life (QoL) as well as easier and earlier access to specialists, genetic testing, patient support programs, and effective treatment options. CONCLUSIONS: The diagnosis, genetic testing, and management pathways among patients with XLRP can vary considerably. There is a need for more standardized diagnosis and management pathways, and QoL assessments, due to the major impact that XLRP has on patients' lives.

Real-world outcomes associated with switching to anti-TNFs versus other biologics in Crohn's Disease patients: A retrospective analysis using German claims data.

Background: The positioning of new biologic agents for the treatment of Crohn's disease (CD) following failure of initial anti-tumor necrosis factor (anti-TNF) therapy remains a challenge in the real world. Objectives: This study aims to investigate the real-world outcomes associated with the sequential use of biologics in CD patients that newly initiate anti-TNFs, specifically comparing those that switch to another anti-TNF versus biologics with other modes of action. Design: Retrospective cohort study. Methods: We identified CD patients who newly began anti-TNF therapy between 1 October 2014 and 31 December 2018 using two German claims databases. Patients were classified as within-class switchers (WCS) if they switched to another anti-TNF or outside-class switchers (OCS) if they switched to vedolizumab (VDZ) or ustekinumab (UST). To compare WCS and OCS, baseline covariates were adjusted through inverse probability of treatment weighting (IPTW), and time-to-event analyses were performed using Cox Proportional Hazard regressions. Results from both databases were meta-analyzed using an inverse variance model. Results: Overall, 376 prevalent adult CD patients who initiated anti-TNFs and switched to another biologic were identified. After IPTW, there were 152 and 177 patients in the WCS and OCS group, respectively. WCS were more likely to receive prolonged corticosteroid therapy [hazard ratio (HR): 1.63, 95% confidence interval (CI): 1.17-2.27, p = 0.004], switch a second time to a different biologic (HR: 2.44, 95% CI: 1.63-3.66, p < 0.001), and discontinue treatment (HR: 1.71, 95% CI: 1.25-2.34, p = 0.001) than OCS. Conclusion: This study suggests that CD patients exhibit more favorable outcomes when switching outside the anti-TNF class to VDZ or UST after initial anti-TNF failure than switching to a second anti-TNF. With loss of response to anti-TNFs as a concern in the real world, comparative evidence from claims data assessing sequential use of biologics can help optimize treatment algorithms of patients after anti-TNF failure.

Objectively assessed disease activity and drug persistence during ustekinumab treatment in a nationwide real-world Crohn's disease cohort.

OBJECTIVE: Long-term evidence on ustekinumab treatment response and persistence in patients with Crohn's disease in a real-world setting is scarce. We performed a retrospective nationwide chart review study of long-term clinical outcomes in Crohn's disease patients treated with ustekinumab. METHODS: The study was conducted in 17 Finnish hospitals and included adult Crohn's disease patients who received an initial intravenous dose of ustekinumab during 2017-2018. Disease activity data were collected at baseline, 16 weeks, and 1 year from health records. RESULTS: The study included 155 patients. The disease was stricturing or penetrating in 69 and 59% had prior Crohn's disease-related surgeries, and 97% had a treatment history of at least one biologic agent. Of 93 patients with ≥1 year of follow-up, 77 (83%) were still on ustekinumab at 1 year. In patients with data available, from baseline to the 1-year follow-up the simple endoscopic score for Crohn's disease (SES-CD) decreased from 10 to 3 (P = 0.033), C-reactive protein from 7 to 5 mg/L, (P < 0.001) and faecal calprotectin from 776 to 305 µg/g (P < 0.001). CONCLUSIONS: Ustekinumab treatment in patients with highly refractory Crohn's disease resulted in high long-term treatment persistence and significantly reduced disease activity, assessed with objective markers for intestinal inflammatory activity.

CCR3, CCR5, interleukin 4, and interferon-gamma expression on synovial and peripheral T cells and monocytes in patients with rheumatoid arthritis.

OBJECTIVE: To characterize cytokine and chemokine receptor profiles of T cells and monocytes in inflamed synovium and peripheral blood (PB) in patients with rheumatoid arthritis (RA) and other arthritides. METHODS: We studied PB and synovial fluid (SF) samples taken from 20 patients with RA and 9 patients with other arthritides. PB cells from 8 healthy adults were used as controls. CCR3, CCR5, and intracellular interferon-g (IFN-g) and interleukin 4 (IL-4) expression in CD8+ and CD8- T cell populations and in CD14+ cells were determined with flow cytometry. RESULTS: Expression of CCR5 and CCR3 by CD8-, CD8+ T cells and CD14+ monocytes was increased in SF compared to PB cells in patients with RA and other arthritides. The number of CD8+ T cells spontaneously expressing IL-4 and IFN-g was higher in SF than in PB in RA patients. Spontaneous CCR5 expression was associated with intracellular IFN-g expression in CD8+ T cells derived from SF in RA. In CD8- T cells the ratio of CCR5+/CCR3+ cells was increased in patients with RA compared to patients with other arthritides. The number of PB CD8- T cells expressing IFN-g after mitogen stimulation was higher in controls than in patients. In PB monocytes the ratio of CCR5+/CCR3+ cells was increased in patients with RA compared to patients with other arthritides and controls. CONCLUSION: T cells and monocytes infiltrating joints in RA and in other arthritides showed increased activation of both type 1 and type 2 immune markers. More pronounced type 1 immune response in joints, shown as an increased CCR5/CCR3 ratio, was found in the patients with RA versus those with other arthritides. Monocytes but not T cells in PB showed increased activation in RA.