Small Bowel Crohn's Disease Recurrence is Common After Total Proctocolectomy for Crohn's Colitis.

BACKGROUND: Surgical intervention for Crohn's disease involving the colon is often a total proctocolectomy with end ileostomy. There are limited data regarding postoperative small bowel recurrence rates in the recent era. OBJECTIVE: The purpose of this study was to determine the rate of small bowel Crohn's disease recurrence following total proctocolectomy and secondarily define risk factors for disease recurrence. DESIGN: This was a retrospective cohort study. SETTINGS: The study was conducted at four hospitals within a single healthcare system. PATIENTS: Patients were those with Crohn's disease undergoing total proctocolectomy with end ileostomy between 2009-2019. MAIN OUTCOME MEASURES: Main outcome measures were clinical, endoscopic, radiographic, and/or surgical Crohn's disease recurrence. RESULTS: In total, 193 patients were included with a median follow-up of 1.8 years (IQR 0.4-4.6). Overall, 74.6% (n = 144) of patients had been previously exposed to biologic therapy, and 51.3% (n = 99) had a history of small bowel Crohn's disease. Postoperatively, 14.5% (n = 28) of patients received biologic therapy. Crohn's disease recurrence occurred in 23.3% (n = 45) of patients with an estimated median 5-year recurrence rate of 40.8% (95% CI' 30.2-51.4). Surgical recurrence occurred in 8.8% (n = 17) of patients with an estimated median 5-year recurrence rate of 16.9% (95% CI' 8.5-25.3). On multivariable analysis, prior small bowel surgery for Crohn's disease (HR 2.61; 95% CI' 1.42-4.81) and Crohn's diagnosis at age <18 years (HR 2.56; 95% CI' 1.40-4.71) were associated with Crohn's recurrence. In patients without prior small bowel Crohn's disease, 14.9% (n = 14) had Crohn's recurrence with an estimated 5-year overall recurrence rate of 31.1% (95% CI' 13.3-45.3) and 5-year surgical recurrence rate of 5.7% (95% CI' 0.0-12.0). LIMITATIONS: The study was limited by its retrospective design and lack of consistent follow-up on all patients. CONCLUSIONS: Greater than one third of patients who underwent total proctocolectomy for Crohn's disease were estimated to have small bowel Crohn's recurrence at 5 years after surgery. Patients with a history of small bowel surgery for Crohn's and diagnosis at any early age may benefit from more intensive postoperative surveillance and consideration for early medical prophylaxis. See Video Abstract at http://links.lww.com/DCR/B762. RECURRENCIA FRECUENTE DE LA ENFERMEDAD DE CROHN DEL INTESTINO DELGADO DESPUS DE LA PROCTOCOLECTOMA TOTAL POR COLITIS DE CROHN: ANTECEDENTES:La cirugia para la enfermedad de Crohn que involucra el colon es a menudo una proctocolectomía total con ileostomía terminal. Hay datos limitados con respecto a las tasas de recurrencia posoperatoria de la enfermedad de Crohn del intestino delgado en la actualidad.OBJETIVO:Buscamos determinar la tasa de recurrencia de la enfermedad de Crohn del intestino delgado después de la proctocolectomía total y, en segundo lugar, definir los factores de riesgo de recurrencia de la enfermedad.DISEÑO:Estudio de cohorte retrospectivo.ENTORNO CLINICO:Cuatro hospitales de un mismo sistema sanitario.PACIENTES:Pacientes con enfermedad de Crohn sometidos a proctocolectomía total con ileostomía terminal entre 2009-2019.PRINCIPALES MEDIDAS DE VALORACIÓN:Recurrencia clínica, endoscópica, radiográfica y / o quirúrgica de la enfermedad de Crohn.RESULTADOS:Se incluyeron 193 pacientes con un seguimiento promedio de 1,8 años (IQR 0,4-4,6). El 74,6% (n = 144) de los pacientes habían recibido previamente terapia biológica y el 51,3% (n = 99) tenían antecedentes de enfermedad de Crohn del intestino delgado. Después de la operación, el 14,5% (n = 28) de los pacientes recibieron terapia biológica. La recurrencia de la enfermedad de Crohn ocurrió en el 23,3% (n = 45) de los pacientes con una tasa de recurrencia media estimada a los 5 años del 40,8% (IC del 95%: 30,2-51,4). La recidiva quirúrgica se produjo en el 8,8% (n = 17) de los pacientes con una tasa de recidiva media estimada a los 5 años del 16,9% (IC del 95%: 8,5-25,3). En el análisis multivariable, la cirugía previa del intestino delgado para la enfermedad de Crohn (HR 2,61, IC del 95%: 1,42-4,81) y el diagnóstico de Crohn a la edad <18 (HR 2,56, IC del 95%: 1,40-4,71) se asociaron con la recurrencia de Crohn. En pacientes sin enfermedad previa de Crohn del intestino delgado, el 14,9% (n = 14) tuvo recurrencia de Crohn con una tasa de recurrencia general estimada a 5 años del 31,1% (IC del 95%: 13,3-45,3) y una tasa de recurrencia quirúrgica a 5 años del 5,7% (IC del 95%: 0,0-12,0).LIMITACIONES:Diseño retrospectivo, falta de seguimiento constante de todos los pacientes.CONCLUSIONES:Se estimó que más de un tercio de los pacientes que se sometieron a proctocolectomía total tenían recurrencia de Crohn del intestino delgado a los 5 años después de la cirugía. Los pacientes con antecedentes de cirugía por enfermedad de Crohn del intestino delgado y diagnóstico a una edad temprana pueden beneficiarse de una vigilancia posoperatoria más intensiva y la consideración de una profilaxis médica temprana. Consulte Video Resumen en http://links.lww.com/DCR/B762. (Traducción- Dr. Ingrid Melo).

Predicting response to anti-TNFα therapy among patients with axial spondyloarthritis (axSpA): results from BSRBR-AS.

OBJECTIVES: While many axSpA patients, eligible to receive anti-TNFα therapy, derive benefit when prescribed them, some patients do not. The current study aims to identify modifiable targets to improve outcome as well as non-modifiable targets that identify groups less likely to derive benefit. METHODS: The BSRBR-AS is a prospective cohort study of axSpA patients who, at recruitment, were naïve to biologic therapy. Those in the 'biologic' sub-cohort commenced their first anti-TNFα therapy at recruitment or during follow-up. Prior to commencement, information was collected on socio-economic, clinical and patient-reported factors. Outcome was assessed according to ASAS20, ASAS40, ASDAS reduction and achieving a moderate/inactive ASDAS disease state. RESULTS: 335 participants commenced their first anti-TNFα therapy and were followed up at a median of 14 (inter-quartile range 12-17) weeks. Response varied between 33% and 52% according to criteria used. Adverse socio-economic factors, fewer years in education predicted lower likelihood of response across outcome measures as did not working full-time. Co-morbidities and poor mental health were clinical and patient-reported factors, respectively, associated with lack of response. The models, particularly those using ASDAS, were good at predicting those who did not respond (negative predictive value (NPV) 77%). CONCLUSION: Some factors predicting non-response (such as mental health) are modifiable but many (such as social/economic factors) are not modifiable in clinic. They do, however, identify patients who are unlikely to benefit from biologic therapy alone. Priority should focus on how these patients receive the benefits that many derive from such therapies.

The landscape of psoriasis provision in the UK.

Psoriasis remains one of the commonest conditions seen in dermatological practice, and its treatment is one of the greatest cost burdens for the UK National Health Service. Treatment of psoriasis is complex, with numerous overlapping lines and therapies used in combination. This complexity reflects the underlying pathophysiology of the disease as well as the heterogeneous population that it affects. National Institute for Health and Care Excellence (NICE) guidance for the treatment of psoriasis has been available since 2013, and has been the subject of three national audits conducted by the British Association of Dermatologists. This report synthesizes the results of the most recent of those exercises and places it in the context of the NICE guidance and previous audits. It clearly shows the significant burden of disease, issues with provision of services and long waiting times and the marked shift in therapies towards targeted biologic therapies.

What's new in atopic eczema? An analysis of systematic reviews published in 2018. Part 2: systemic therapies.

This review forms part of an annual update series on atopic eczema (AE), where systematic reviews (SRs) are gathered and appraised to provide a summary of key recent research findings. The focus of this article is systemic therapies used in AE, while a review on prevention and topical therapies is provided in Part 1. In total, 17 SRs on various systemic treatments used in AE were first published or indexed in 2018. There is a lack of evidence to support vitamin D supplementation, montelukast and naltrexone in AE treatment. The adverse effects of systemic corticosteroids are the main barrier to their use, and there is also a lack of data to determine the optimal delivery and duration of treatment with them. Of other immunosuppressants, ciclosporin has the most robust evidence of efficacy. Biologic therapies in AE treatment are being increasingly investigated, and to date, the greatest quantity of data and evidence of efficacy relates to dupilumab. The most commonly reported adverse effects are injection-site reactions and conjunctivitis. Other biologics showing some evidence of efficacy include nemolizumab, lebrikizumab and tralokinumab, although further data are needed. There are currently insufficient data on oral small molecules, including Janus kinase inhibitors, in the treatment of AE. A Cochrane review on probiotics showed no significant benefit, and SRs and meta-analyses on complementary and alternative medicines, including probiotics, in paediatric AE demonstrated significant heterogeneity, thereby limiting their interpretation. This summary of recent SRs provides up-to-date evidence for clinicians on systemic therapies in AE.

A Six-Year Analysis of Biological Therapy for Severe Psoriasis in a Lithuanian Reference Centre of Dermatovenereology.

Background and Objectives: Biological therapy is widely used for the treatment of severe psoriasis. The objective of this study was to evaluate the efficacy and safety of biological therapy for patients with severe psoriasis. Materials and Methods: A retrospective study of 79 patients with severe psoriasis, who have been treated with biological therapy between 2012 and 2018, was conducted. During this study, the following data were collected and evaluated: sex, age, body mass index (BMI), duration of illness, the results of treatment with biological therapy, concomitant therapy, Psoriasis Area and Severity Index (PASI) and adverse events. Results: In total, 74.7% (n = 59) of subjects were male. Their overall average age was 47.4 ± 11.4 (range: 18-73) years. Their baseline BMI was 27.6 ± 5.9, which increased to 29.6 ± 4.5 after 6 years of treatment. The mean duration of psoriasis was 25.7 ± 12.5 years. In total, 39.2% (n = 31) of subjects received infliximab, 36.7% (n = 29)-etanercept, 24.1% (n = 19)-ustekinumab. The treatment duration for infliximab, etanercept and ustekinumab was 201.6 ± 86.8, 156.2 ± 137.4 and 219.1 ± 95.7 weeks (p < 0.01), respectively. Overall, 65.8% (n = 52) of subjects were also on methotrexate; 30.8% (n = 16) of them discontinued it due to clinical improvement (31.3% (n = 5)), impaired liver function (31.3% (n = 5)), and intolerance (25% (n = 4)). Baseline PASI was 20.8 ± 8.8. PASI 50 was achieved by 96.2% (n = 76) of patients at week 11, PASI 75 by 86.1% (n = 68) at week 16, PASI 90 by 54.4% (n = 43) at week 35, and PASI 100 by 13.9% (n = 11) at week 33. The overall incidence rate of adverse events was 0.362 per patient year of follow-up. Conclusion: Biological therapy is an effective and safe treatment for patients with severe psoriasis.

Autologous Blood Patch Injection versus Hydrogel Plug in CT-guided Lung Biopsy: A Prospective Randomized Trial.

Purpose To compare the effect of autologous blood patch injection (ABPI) with that of a hydrogel plug on the rate of pneumothorax at CT-guided percutaneous lung biopsy. Materials and Methods In this prospective randomized controlled trial ( https://ClinicalTrials.gov , NCT02224924), a noninferiority design was used for ABPI, with a 10% noninferiority margin when compared with the hydrogel plug, with the primary outcome of pneumothorax rate within 2 hours of biopsy. A type I error rate of 0.05 and 90% power were specified with a target study population of 552 participants (276 in each arm). From October 2014 to February 2017, all potential study participants referred for CT-guided lung biopsy (n = 2052) were assessed for enrollment. Results The data safety monitoring board recommended the trial be closed to accrual after an interim analysis met prespecified criteria for early stopping based on noninferiority. The final study group consisted of 453 participants who were randomly assigned to the ABPI (n = 226) or hydrogel plug (n = 227) arms. Of these, 407 underwent lung biopsy. Pneumothorax rates within 2 hours of biopsy were 21% (42 of 199) and 29% (60 of 208); chest tube rates were 9% (18 of 199) and 13% (27 of 208); and delayed pneumothorax rates within 2 weeks after biopsy were 1.4% (three of 199) and 1.5% (three of 208) in the ABPI and hydrogel plug arms, respectively. Conclusion Autologous blood patch injection is noninferior to a hydrogel plug regarding the rate of pneumothorax after CT-guided percutaneous lung biopsy. © RSNA, 2018 Online supplemental material is available for this article.

Regional differences in anti-TNF-α therapy and surgery in the treatment of inflammatory bowel disease patients: a Norwegian nationwide cohort study.

BACKGROUND AND AIMS: During the last decades, substantial progress has been made in both medical and surgical treatment of inflammatory bowel disease (IBD). The aim of this study was to determine the use of anti-TNFs and surgery during the first 3 years after diagnosis in IBD patients across the four health regions in Norway using nationwide patient registry data. METHODS: This study used nationwide data from the Norwegian Patient Registry. Cumulative incidence of anti-TNF exposure and major surgery was calculated for patients diagnosed in 2010-2012. The analyses were stratified by diagnosis and health region. All patients were followed for an equal period of 3 years from diagnosis. RESULTS: The study population included 8,257 IBD patients first registered between 2010 and 2012, of whom 2,829 were diagnosed with Crohn's disease (CD) and 5,428 with ulcerative colitis (UC). Across Norway's health regions, the cumulative incidence of major surgery after 3 years varied from 11.4% to 17.1% for CD and from 4.6% to 6.9% for UC. The cumulative incidence of anti-TNF exposure varied from 20.9% to 31.4% for CD and from 8.0% to 13.5% for UC. The region with the lowest anti-TNF use had the highest surgery rates for both UC and CD. CONCLUSIONS: Cumulative incidence of anti-TNF exposure and surgery varied significantly across Norway's health regions during the three first years after IBD diagnosis.

Persistence rates and medical costs of biological therapies for psoriasis treatment in Japan: a real-world data study using a claims database.

BACKGROUND: Biological therapies (BTs) including infliximab (IFX), adalimumab (ADL), secukinumab (SCK) and ustekinumab (UST) are approved in Japan for the treatment of psoriasis. Although the persistence rates and medical costs of BTs treatment have been investigated in multiple foreign studies in recent years, few such studies have been conducted in Japan and the differences between patients who adhered to treatment and those who did not have not been reported. This study is aimed at investigating the persistence rates and medical costs of BTs in the treatment of psoriasis in Japan, using the real-world data from a large-scale claims database. METHODS: Claims data from the JMDC database (August 2009 to December 2016) were used for this analysis. Patient data were extracted using the ICD10 code for psoriasis and claims records of BT injections. Twelve-month and 24-month persistence rates of BTs were estimated by Kaplan-Meier methodology, and 12-month-medical costs before and after BT initiation were compared between persistent and non-persistent patient groups at 12 months. RESULTS: A total of 205 psoriasis patients treated with BTs (BT-naïve patients: 177) were identified. The 12-month/24-month persistence rates for ADL, IFX, SCK, and UST in BT-naïve patients were 46.8% ± 16.6%/46.8 ± 16.6%, 53.0% ± 14.9%/41.0% ± 15.5%, 55.4%/55.4% (95% CI not available) and 79.4% ± 9.9%/71.9% ± 12.2%, respectively. Statistically significant differences in persistence were found among different BT treatments, and UST was found to have the highest persistence rate. The total medical costs during the 12 months after BT initiation in BT-naïve patients were (in 1000 Japanese Yen): 2218 for ADL, 3409 for IFX, 465 for SCK, 2824 for UST (average: 2828). Compared with the 12-month persistent patient group, the total medical costs in the persistent group was higher (Δ:+ 118), but for some medications such as IFX or UST cost increases were lower for persistent patients. CONCLUSIONS: UST was found to have the highest persistence rate among all BTs for psoriasis treatment in Japan. The 12-month medical costs after BT initiation in the persistent patient group may not have increased as much as in the non-persistent patient group for some medications.

Persistency of Biologic Therapies for Plaque Psoriasis in 2 Large Community Practices.

BACKGROUND: Biologics have transformed the management of moderate to severe psoriasis. The persistency of biologics lacks real-world data. OBJECTIVES: To quantify drug survival of infliximab (IFX), adalimumab (ADA), etanercept (ETA), and ustekinumab (UST) and to identify potential factors affecting drug survival. METHODS: An observational, retrospective 2-centre study consisting of 906 patients from private practices in Ontario between July 2003 and June 13, 2016, was conducted, including patients with plaque psoriasis receiving commercial treatment with ADA, ETA, IFX, and UST. Paper and electronic records of each patient were reviewed. RESULTS: Median survival times for UST, IFX, ADA, and ETA were respectively, in months, 68, 23, 33, and 28. Female sex was determined to be a statistically significant positive predictor of drug survival. Our study was consistent with the literature in that UST had the highest survival rate compared to the other biologics, and the shape of our drug survival curve suggested that loss of drug efficacy is a stochastic occurrence. Compared to other studies, our data exhibited lower survival rates at various time points for all the biologics studied, and female sex did not predict drug survival in other studies. We also investigated potential reasons for differences in biologic survival times between different practices; the main differentiator was drug dosage, as higher dosages were associated with greater survival. CONCLUSION: UST has a higher drug survival rate than ADA, ETA, and IFX, as observed in other studies. When practice patterns are compared, dosage difference is the main factor that may cause differing survival rates.

High rate of serious infection in juvenile idiopathic arthritis patients under biologic therapy in a real-life setting.

OBJECTIVES: To assess the rate of serious and/or opportunistic infections in juvenile idiopathic arthritis (JIA) patients from a single tertiary center under biologic therapy and to identify possible risk factors associated to these complications. METHODS: A total of 107 JIA patients followed at the biologic therapy center of our tertiary university hospital using a standardized electronic database protocol including demographic data, clinical and laboratorial findings and treatment at baseline and at the moment of infection. Opportunistic infections included tuberculosis, herpes zoster and systemic mycosis. RESULTS: A total of 398 patient-yrs(py) were included. The median time of biologic exposure was 3.0 years (0.15-11.5). We observed 35 serious/opportunistic infectious events in 27 (25%) patients: 31(88.6%) were serious infections and four (11.4%) opportunistic infections. Serious/opportunistic infections rates were 10.6/100py for ETN, 10.9/100py for ADA, 2.6/100py for ABA and 14.8/100py for TCZ. Comparison of 27 patients with and 80 without infection showed a higher frequency of systemic-onset JIA, lower age at biologic therapy initiation and a history of previous serious infection (p < .05) in the former group. CONCLUSIONS: This study demonstrated a high rate of serious infections in JIA patients under biologic therapy in a real-life setting. Systemic-onset JIA, lower age at biologic therapy start and history of previous serious infections were important risk factors for these complications. Also, higher rates of severe infections comparing to the former studies was possibly due to elevated MTX doses in our patients.

Surgical rates in the era of biological therapy: up, down or unchanged?

PURPOSE OF REVIEW: The aim of this review is to summarize data regarding surgical trends in inflammatory bowel disease in the prebiologic and biologic era, with a focus on population-based studies and randomized controlled trials (RCTs). RECENT FINDINGS: There is paucity of data in RCTs regarding surgical rates, with only a few clinical trials reporting them. From the available data, meta-analyses of RCTs have concluded that antitumor necrosis α agents (anti-TNF) reduce surgical rates in ulcerative colitis and Crohn's disease. A large body of evidence from population-based studies from different regions of the world is available to evaluate surgical trends before and after the introduction of anti-TNF agents. The risk of surgery decreased significantly over the past six decades; these decreasing trends continued in the biologic era, which might indicate a potential beneficial disease-modifying effect of biologics. There is lack of data with nonanti-TNF biologics (i.e. anti-integrins and ustekinumab) regarding the risk of surgery. SUMMARY: Although data from population-based studies and available RCTs suggest a protective effect from surgery of anti-TNF agents, definitive conclusions should be drawn only when more disease-modifying trials with different biologics and treatment strategies become available.

Patterns of biologic therapy use in the management of psoriasis: cohort study from the British Association of Dermatologists Biologic Interventions Register (BADBIR).

BACKGROUND: Treatment modifications, including dose escalations, dose reductions, switches, discontinuations and restarts of biologics may be necessary in the management of psoriasis but the patterns of usage are incompletely defined. OBJECTIVES: To examine the treatment utilization patterns of adalimumab, etanercept and ustekinumab among biologic-naïve and non-naïve patients with psoriasis enrolled in the British Association of Dermatologists Biologic Interventions Register (BADBIR). METHODS: The study cohort included adults with chronic plaque psoriasis who were followed up for ≥ 12 months. Treatment modifications were assessed during the first year of therapy. The time-trend method, comparing the cumulative dose (CD) patients received with the recommended cumulative dose (RCD), was used to assess dosing patterns. Concomitant use of other systemic treatments was also examined. RESULTS: In total, 2980 patients (adalimumab: 1675; etanercept: 996; ustekinumab: 309) were included; 79·2% were biologic-naïve. Over 12 months, 77·4% of patients continued the biologic, 2·6% restarted therapy after a break of ≥ 90 days, 2·5% discontinued, and 17·5% switched biologic therapy. Most patients (85·7%) received the RCD of the biologic, although 8·1% were exposed to a higher CD. In total, 749 (25·1%) patients used conventional systemic therapies concomitantly with a biologic at some stage; methotrexate was used most commonly (458; 61·2%). Of those using combination therapy, 454 (60·6%) continued the use of the conventional systemic therapy for > 120 days after the start of the biologic. CONCLUSIONS: More than one-third of patients experienced treatment modifications within the first year of initiating a biologic. Conventional systemic therapies, particularly methotrexate, were commonly used concurrently, which should be considered when evaluating treatment response and adverse events to biologics in real-world observational studies.

What Can We Learn from Epidemiological Studies in Inflammatory Bowel Disease?

BACKGROUND: Population-based studies represent the whole spectrum of patient population and should represent the mainstay when evaluating patients' prognosis. A high number of CD patients need surgical intervention during the disease course. The disease course of inflammatory bowel diseases, including ulcerative colitis (UC) and Crohn's disease (CD), is quite varied and still quite unpredictable. Key Messages: According to earlier studies, up to 60% of patients undergo at least one operation after 10 years of CD duration. Newer cohorts report lower cumulative probability of surgery of approximately 40% after 10 years. The colectomy rate in UC is approximately 10% after 10 years from diagnosis with a geographic difference. Similarly to CD, the colectomy rate seems to decrease over time. There is some evidence that the increasing use of immunosuppressive and/or biological therapy might have been responsible for this favourable trend. However, other factors may have an impact on decreasing surgical trend over time. The relative risk (RR) of colorectal cancer (CRC) in UC is approximately doubled compared to background population. However, the absolute risk in general is relatively low between 1.1 and 5.3% after 20 years of disease duration. Furthermore, a decreasing trend in the incidence of CRC has been reported in recent studies. Importantly, several factors such as disease extent, activity, age at UC onset, and so on may increase/modify an individual risk. Similar to UC, CD patients have approximately 2 times higher RR of cancer compared to background population. The risk is higher for colon than for rectum cancer and present only in CD patients with colonic involvement. CONCLUSIONS: The surgery rate in CD has decreased over the time period. The evidence on colectomy rate in UC is less conclusive. The RR of CRC in UC and CD is approximately doubled compared to that of the background population, but it seems to be decreasing in more recent cohorts.

Do Biologic Therapies for Rheumatoid Arthritis Offset Treatment-Related Resource Utilization and Cost? A Review of the Literature and an Instrumental Variable Analysis.

PURPOSE OF REVIEW: One justification for using expensive biologic therapy in rheumatoid arthritis (RA) has been that it can reduce future healthcare utilization such as joint surgeries and physician visits. However, the evidence to support this assertion is unclear. We conducted a review of the literature for studies which have analyzed the trends in resource use of RA patients, and then undertook a retrospective observational analysis of a Canadian administrative database using instrumental variable methods. RECENT FINDINGS: Our review found a trend in reduced resource utilization prior to the introduction of biologics and no evidence that biologic therapies have specifically contributed to this reduction. Our observational analysis, which overcame some of the epidemiological challenges with determining the influence of biologics on resource utilization, found a possible reduction in other medications but possible increases rather than decreases in physician visits and hospitalizations. However, our sample was not sufficiently large to make definitive conclusions. Over 15 years since the introduction of biologics for RA, no evidence exists supporting the assumption that biologic therapies reduce future healthcare utilization. While such a question is challenging to generate evidence for, and so an absence of evidence does not suggest that the hypothesis is incorrect, an instrumental variable analysis using sufficient data could provide definitive evidence.

Frequency of the use of biological treatment of patients with rheumatoid arthritis and ankylosing spondylitis in Lower Silesia.

BACKGROUND: Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are chronic connective tissue diseases. Inadequate treatment of RA and AS results in health failure, disability and premature death. In recent years, development of immunology and genetic engineering techniques has started a new generation of drugs in the treatment of RA and AS, called biologic response modifiers or biologics. It is a very effective therapy of serious RA and AS. In many cases, they represent the only way to improve the quality of life, slowing or even arresting the development of these diseases. According to national statistics, the percentage of patients with rheumatic diseases treated with biologic treatment in Poland is less than 1.5%, and it is much lower than in Western European countries (20%). PURPOSE: The aim of the study was to evaluate the use of biological treatment in Lower Silesia in patients with RA and AS in the years 2006-2015, based on data obtained from the Lower Silesian Branch of the Polish National Health Fund. RESULTS AND CONCLUSIONS: In the last 10 years the frequency of biological treatment of RA or AS in Lower Silesia was estimated as 2.06% of patients (in 2011) to 6.03% of patients (during the first 8 months of 2015). Biological treatment is more often used in Lower Silesia in comparison to national statistics and ranks at a similar level as in other countries of Central and Eastern Europe.

Adherence to biologic therapies and associated factors in rheumatoid arthritis, spondyloarthritis and psoriatic arthritis: a systematic literature review.

OBJECTIVES: To analyse the evidence on adherence to biologic therapies in rheumatoid arthris (RA), spondyloarthritis (SpA), and psoriatic arthritis (PsA). METHODS: Systematic review of studies retrieved by a sensitive search strategy in MEDLINE database (1961 through March 2012). To be selected, studies had to include patients with RA, SpA, or PsA, treatment with intravenous or subcutaneous biologic therapies, and had to report on measures of adherence. By design, only randomised controlled trials (RCT) or high quality cohort studies with a control group were selected. RESULTS: A total of 24 studies were included, of which 12 reported results from national or local biologic registers, 9 were retrospective studies, 2 prospective studies, and only one was an RCT. Patients included were mostly women with diagnosis of RA or SpA and, less frequently, PsA. There was a great variability in the definition of adherence, measurement methods, and associated factors analysed. In general, adherence to etanercept was superior to that of other biologics, by the measures utilised. The main predictive factors - age, sex, comorbidity, baseline clinical condition, previous or concomitant use of DMARDs, anti-TNF in monotherapy or in combination with MTX - produced diverse, even divergent results across studies. CONCLUSIONS: There is a wide variability related to the adherence concept and its measurement, reflecting the complexity of the phenomenon. In order to draw more consistent conclusions about the relative value of predictive factors on adherence and persistence of biological therapy, larger controlled studies with better selection of variables and analysis of interactions are needed.

Apparent discrimination in the provision of biologic therapy to patients with Crohn's disease according to ethnicity.

OBJECTIVES: The objective of the study was to investigate whether patients from a South Asian ethnic background who had Crohn's disease received equivalent access to therapy with biologics compared to patients with an English background. STUDY DESIGN: The study was retrospective and covered the period 2008 to 2012. It was based on a register of all patients with Crohn's disease in Leicestershire who are treated with biologics. The prevalence of Crohn's disease in Leicestershire amongst South Asian and English patients was known from earlier studies and from these data it was possible to make corrections to allow for the difference in frequency of the condition between the two communities. METHODS: All adult patients who received biologics for treatment of Crohn's disease in Leicestershire between 2008 and 2012 were reviewed and their gender and ethnicity noted as well as whether they had received infliximab or adalumimab. The expected numbers of patients who should have received these therapies were calculated in two ways: RESULTS: One hundred and twenty six patients with Crohn's disease who received treatment with biologics were European and 13 South Asian. The patients' gender was also noted and 67 European patients (53%) were female as were six Asians (46%). Based on prevalence data, the expected distribution of the treatment would have been for 97 of the patients to have been European and 42 to have been South Asian. If 126 European patients warranted treatment, on this basis the expected number of South Asian patients in need of biologic therapy would have been 55. Based on the smaller predicted number of South Asian patients (42) the difference is significant at P < 0.0001 [Proportion difference=0.69 (95% confidence interval=0.539278-0.809576]. For the difference to be extinguished the number of English patients who should have received biologic therapy would have been as low as between 30 and 39 cases (based on the calculated proportion of 97 and the actual figure of 126 European patients respectively). Based on a population composition, rather than prevalence data, in which 24% of the Leicester community should have been of South Asian origin, 33 patients would have received biologics compared with 92 patients of English origin (66%). This is significantly different to the 13 patients who did receive treatment (z=-3.2, P < 0.001). CONCLUSIONS: Suggested reasons for these differences have included concerns about the animal origins of infliximab as well as difficulties associated with accessing the service, such as the provision of information in an appropriate language through appropriate media. For those who come from groups with significant social deprivation there is often a readiness to accept more limited clinical services. However, such differences themselves, are examples of discrimination in clinical practice.

Adherence to Anti-Tumor Necrosis Factor Therapy Administered Subcutaneously and Associated Factors in Patients With Rheumatoid Arthritis.

BACKGROUND: Adherence to biologic therapy is relatively poorly studied in rheumatoid arthritis (RA) because many of the studies have investigated the drug persistence, which represents only a surrogate of adherence. OBJECTIVES: The aims of this study were to determine the extent of adherence in RA patients with subcutaneously administered anti-tumor necrosis factor methotrexate agents and to identify the risk factors for nonadherence. METHODS: A cohort of RA patients who started a subcutaneous anti-tumor necrosis factor treatment were enrolled. After 12 months of treatment, all patients completed the 4-item Morisky Medication Adherence Scale questionnaire. Associations between beliefs and nonadherence and the influence of demographic, clinical, and radiographic features were assessed using logistic regression model. RESULTS: A total of 209 (80.4%) of the 260 patients were included in the analyses. Forty-three of 209 patients were considered nonadherent to their medication (20.6%) according to the 4-item Morisky Medication Adherence Scale. More than half (53.1%) of patients showed at least 1 form of nonadherent behavior.The logistic model showed that low disease activity (P = 0.003), higher patient-physician discordance ratings (P = 0.012), older age (P = 0.041), and a high number of comorbid conditions (P = 0.011) were significantly associated with increased likelihood of nonadherence. CONCLUSIONS: The overall nonadherence with subcutaneous biologic therapy is relatively high among RA patients and should be taken into account when a patient's response to treatment is unsatisfactory.

In-/off-label use of biologic therapy in systemic lupus erythematosus.

Current therapies for systemic lupus erythematosus (SLE) include corticosteroids as a persistent mainstay and traditional immunosuppressants which are given according to disease severity, organ involvement and patient status. No treatment entails certain efficacy devoid of mild-to-moderate adverse effects. Nowadays, novel therapies are being developed aiming to target specific molecules involved in SLE development and progression which show variable effectiveness and safety. Biologic agents considered for SLE comprise monoclonal antibodies (chimeric, humanized or fully human) as well as fusion molecules or antibody fragments mostly consisting of B cell-targeted therapies beside anti-cytokines as well as T cell-targeted therapies. Encouraging evidence on biologics is mostly provided by case series or uncontrolled studies; conversely, larger randomized controlled clinical trials have frequently missed their primary endpoints with the exception of BLISS-52 and BLISS-76 trials. Actually, apart from belimumab, biologics are employed in clinical practice as off-label treatments for lupus and results are often promising, depending on specific SLE features, dose regimens and individual responsiveness.

Inequities in access to biologic and synthetic DMARDs across 46 European countries.

OBJECTIVES: We investigated access to biologic and synthetic disease modifying drugs (bDMARDs and sDMARDs) in patients with rheumatoid arthritis (RA) across Europe. METHODS: A cross-sectional study at national level was performed in 49 European countries. A questionnaire was sent to one expert, addressing the number of approved and reimbursed bDMARDs and sDMARDs, prices and co-payments, as well as acceptability of bDMARDs (barriers). Data on socio-economic welfare (gross domestic product per capita (GDP), health expenditure, income) were retrieved from web-based sources. Data on health status of RA patients were retrieved from an observational study. Dimensions of access (availability, affordability and acceptability) were correlated with the country's welfare and RA health status. RESULTS: In total, 46 countries (94%) participated. Six countries did not reimburse any of the five sDMARDs surveyed, and in ten countries no bDMARDs were reimbursed. While the price of annual treatment with an average sDMARD was never higher than GPD, the price of one year treatment with a bDMARD exceeded GPD in 26 countries. Perceived barriers for access to bDMARDs were mainly found among financial and administrative restrictions. All dimensions of access were positively correlated with the country's economic welfare (coefficients 0.69 to 0.86 for overall access scores). CONCLUSIONS: Patients with RA in lower income European countries have less access to bDMARDs and sDMARDs, with particularly striking unaffordability of bDMARDs in some of these countries. When accepting that sDMARDs and bDMARDs are equally needed across countries to treat RA, our data point to inequities in access to pharmacological treatment for RA in Europe.