Biologics Register Research Articles

227 Real-world drug discontinuation of acitretin (ACI), ciclosporin (CsA), fumaric acid esters (FAE) and methotrexate (MTX) in patients with moderate-severe psoriasis

Real-world discontinuation of ACI, CsA, FAE and MTX in patients with moderate-severe psoriasis is poorly characterised. The aim of this study was to determine whether treatment history affects the discontinuation rates of these therapies. The British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) is a pharmacovigilance register of systemic therapies for psoriasis. In total, 4115 patients registering to BADBIR from 2007-2017 on ACI, CsA, FAE or MTX with at least 6 months of follow-up were analysed. Exposure time was calculated from initiation to: discontinuation date; censor at the latest follow-up; or death. Patients were categorised as incident (first systemic), prevalent (previously prescribed registration therapy), or previous systemic users (previously prescribed another systemic). Cumulative incidence was used to determine the mean proportion (%) of patients discontinuing therapy in the first two years of follow-up. In total, 767 (19%), 1022 (25%), 335 (8%) and 1991 (48%) patients registered to ACI, CsA, FAE and MTX, respectively. The proportions of incident, prevalent and previous systemic users, respectively, were similar for ACI (42%; 16%; 42%), CsA (38%; 16%; 46%) and MTX (41%; 18%; 41%) with 66% previous systemic users registering on FAE (19% incident; 15% prevalent). The overall mean discontinuation rates at two years were: 31% ACI (95% confidence interval 27-34), 41% CsA (38-45), 27% FAE (19-43) and 26% MTX (23-28) for incident users; 33% ACI (27-39), 40% CsA (35-44), 34% FAE (25-46) and 26% MTX (23-29) for prevalent users; and 36% ACI (33-40), 39% CsA (36-42), 35% FAE (31-39) and 31% MTX (29-33) for previous systemic users, respectively. In conclusion, patients with previous systemic use prior to ACI or MTX registration had higher discontinuation rates than incident or prevalent users. These findings require further exploration to determine if stop reasons or predictors of treatment discontinuation differ between categories.

Polypharmacy is associated with treatment response and serious adverse events: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis.

To evaluate whether polypharmacy is associated with treatment response and serious adverse events (SAEs) in patients with RA using data from the British Society for Rheumatology Biologics Register (BSRBR-RA). The BSRBR-RA is a prospective observational cohort study of biologic therapy starters and a DMARD comparator arm. A logistic regression model was used to calculate the odds of a EULAR 'good response' after 12 months of biologic therapy by medication count. Cox proportional hazards models were used to identify risk of SAEs. The utility of the models were compared with the Rheumatic Disease Comorbidity Index using Receiver Operator Characteristic and Harrell's C statistic. The analysis included 22 005 patients, of which 83% were initiated on biologics. Each additional medication reduced the odds of a EULAR good response by 8% [odds ratios 0.92 (95% CI 0.91, 0.93) P < 0.001] and 3% in the adjusted model [adjusted odds ratios 0.97 (95% CI 0.95, 0.98) P < 0.001]. The Receiver Operator Characteristic demonstrated significantly greater areas under the curve with the polypharmacy model than the Rheumatic Disease Comorbidity Index. There were 12 547 SAEs reported in 7286 patients. Each additional medication equated to a 13% increased risk of an SAE [hazard ratio 1.13 (95% CI 1.12, 1.13) P < 0.001] and 6% in the adjusted model [adjusted hazard ratio 1.06 (95% CI 1.05, 1.07) P < 0.001]. Predictive values for SAEs were comparable between the polypharmacy and Rheumatic Disease Comorbidity Index model. Polypharmacy is a simple but valuable predictor of clinical outcomes in patients with RA. This study supports medication count as a valid measure for use in epidemiologic analyses.

Occult HBV infection may negatively impact on drug survival in patients with rheumatoid arthritis on treatment with a first biologic drug. An appraisal from the Biologic Apulian Registry (BIOPURE).

We performed a retrospective analysis to evaluate the survival on first line biologic drug of rheumatoid arthritis (RA) patients with potential occult HBV infection (pOBI). We analysed longitudinal data of 486 consecutive RA patients starting a first biological drug in a time frame from 1st January 2008 to 31st December 2014. Demographic and disease related characteristics were collected at baseline and at the last observation visit. Baseline serological markers of HBV infection and causes of treatment discontinuation were also recorded. Primary endpoint was the influence of pOBI on drug survival, estimated by Kaplan-Meier life table analysis. Estimates hazard ratios (HRs) of drug discontinuation, adjusted for disease characteristics, biological drug class and HBcAb status were computed by Cox-regression models. The retention rate was significantly lower in pOBI positive patients (58.2%) when compared to pOBI negative ones (67.8%) and this data was confirmed also when only discontinuation due to ineffectiveness was considered (pOBI positive 66.4% vs pOBI negative 75.3%, long rank 7.93, p=0.005). Cox regression models showed a significant association between HBcAb-neg (HR 0.58, 0.41-0.84), higher ESR-DAS28 at baseline (HR 1.07, 1.03-1.11) or RF/ACPA-neg (HR 1.46, 1.04-2.06) and drug discontinuation. Occult HBV infection seems to influence negatively the effectiveness of biological therapies in RA patients.

064 Early experience with JAK inhibitor prescribing in the UK: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA)

064 Early experience with JAK inhibitor prescribing in the UK: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA)

242 Baseline characteristics of patients with lupus nephritis requiring rituximab therapy: results from the British Isles Lupus Assessment Group Biologics Register (BILAG-BR)

242 Baseline characteristics of patients with lupus nephritis requiring rituximab therapy: results from the British Isles Lupus Assessment Group Biologics Register (BILAG-BR)

O19 The association of biologic drug-levels with infection risk: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA)

O19 The association of biologic drug-levels with infection risk: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA)

O20 The impact of axial spondyloarthritis on work productivity in individuals living in rural areas: results from the British Society for Rheumatology Biologics Register for Ankylosing Spondylitis (BSRBR-AS)

O20 The impact of axial spondyloarthritis on work productivity in individuals living in rural areas: results from the British Society for Rheumatology Biologics Register for Ankylosing Spondylitis (BSRBR-AS)

Telenomus remus, a Candidate Parasitoid for the Biological Control of Spodoptera frugiperda in Africa, is already Present on the Continent

The fall armyworm, Spodoptera frugiperda, a moth originating from tropical and subtropical America, has recently become a serious pest of cereals in sub-Saharan Africa. Biological control offers an economically and environmentally safer alternative to synthetic insecticides that are being used for the management of this pest. Consequently, various biological control options are being considered, including the introduction of Telenomus remus, the main egg parasitoid of S. frugiperda in the Americas, where it is already used in augmentative biological control programmes. During surveys in South, West, and East Africa, parasitized egg masses of S. frugiperda were collected, and the emerged parasitoids were identified through morphological observations and molecular analyses as T. remus. The presence of T. remus in Africa in at least five countries provides a great opportunity to develop augmentative biological control methods and register the parasitoid against S. frugiperda. Surveys should be carried out throughout Africa to assess the present distribution of T. remus on the continent, and the parasitoid could be re-distributed in the regions where it is absent, following national and international regulations. Classical biological control should focus on the importation of larval parasitoids from the Americas.

RABBIT-SpA: anew disease register for axial spondyloarthritis and psoriatic arthritis

The treatment of axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) has changed enormously in recent years due to market authorization of anumber of new biologicals with different modes of action and the increasing use of biosimilars. Real-world data on long-term safety and efficacy under routine daily conditions is not yet sufficient. Therefore, the German Rheumatism Research Center has initiated anew cohort study covering axSpA and PsA. Presentation of initial results from the new register RABBIT-SpA, which was started in May 2017. This is a prospective longitudinal cohort study with asimilar study design to the German biologics register RABBIT. Patients can be included at the start of anew treatment either in the so-called index drug group or in the comparison group (conventional systemic treatment, including non-steroidal anti-inflammatory drugs, NSAID). Follow-up per patient should be at least 5years and preferably 10years. The RABBIT-SpA uses aweb-based documentation system. Up to mid-December 2018 a total of 514 axSpA patients had been documented in RABBIT-SpA, 410 with an index drug and 104 with conventional treatment. There are differences between these treatment groups, e. g. in the duration of the disease and in parameters of disease activity. It is also noticeable that in axSpA patients, approximately 5years lie between the onset of the symptoms and confirmation of the diagnosis. Of the 355 PsA patients, 265 were included with an index drug and 90 with conventional treatment. Of the PsA patients 86% have adominant peripheral manifestation. The average number of pressure tender joints is8 and the average number of swollen joints is4. The online register RABBIT-SpA is well-received by the participating rheumatological institutions. The electronic recording of patient data can be carried out in areasonable time. Participation in the RABBIT-SpA is open to new rheumatological institutions at any time.

British Association of Dermatologists Biologic Interventions Register delivers: infliximab increases risk of serious infections.

British Association of Dermatologists Biologic Interventions Register delivers: infliximab increases risk of serious infections.

The daily rhythm of activity of corporal biologically active points of cattle in control, with chronic bronchopneumonia and castration

Bioenergy studies have shown that daily rhythms of activity of corporate biologically active points of cattle in clinically healthy animals, with chronic bronchopneumonia and castration differ significantly. The current imbalance of life energy in internal organs of animals in accordance with the internal biological clock registers depending on the pathology in the vital points of the nearest part of the body in relation to the epicenter of the stress factor. So, in chronic bronchopneumonia, it is the canal of the lungs, and when castrated, it is the bladder. Biologically active points 52, 51, 10 - 17, 21, 24 and 97 were the most informative. According to the results of the experiment, “corridor of the norm” of life points biopotentials is approximately 9 – 10 µa. Test voltage up to 2 V was recorded in healthy and up to 3 V - in sick animals.

Change in PsAID-12 scores in patients continuing or discontinuing anti-TNF treatments in psoriatic arthritis: results from the HUR-BIO biologic registry.

Psoriatic Arthritis Impact of Disease 12-item questionnaire (PsAID-12) has been developed to be used in psoriatic arthritis in daily practice. The aim of the present study was to assess the change values of PsAID-12 in PsA patients continuing or discontinuing anti-TNF treatment. We recruited patients from the Hacettepe University biological database (HUR-BIO). Overall, 70 PsA patients had PsAID-12 score before the initiation of the first anti-TNF treatment. Stopping or switching the anti-TNF treatment due to inefficacy was definitely considered a negative response. Changes were evaluated by the comparison with the baseline PsAID-12 score in compliance with the favorable and unfavorable responses to anti-TNF treatments. The standardized response mean (SRM) was used for determining the response. Seventy (78.6% female) patients were analyzed and their mean age was 45.5years (12.0years). The mean follow-up duration was 18.3months (12.6months). At baseline, the mean PsAID-12 score was 6.6 (1.5). Physicians stopped or switched the treatment in 28 patients (40.0%) due to the inefficacy of anti-TNF treatment. The ΔPsAID-12 score was 0.25 (1.71) in the patients discontinuing anti-TNF treatment and 3.52 (2.31) in the patients continuing their anti-TNF treatment (p < 0.001). The SRM scores higher for PsAID-12, particularly in the well response to anti-TNF treatments. A decrease of 3.5units in PsAID-12 score shows a favorable response to anti-TNF treatment. Changes in PsAID-12 score had well discrimination capacity for anti-TNF treatments.

Development and validation of a multivariable risk prediction model for serious infection in patients with psoriasis receiving systemic therapy.

SummaryBackgroundPatients with psoriasis are often concerned about the risk of serious infection associated with systemic psoriasis treatments.ObjectivesTo develop and externally validate a prediction model for serious infection in patients with psoriasis within 1 year of starting systemic therapies.MethodsThe risk prediction model was developed using the British Association of Dermatologists Biologic Interventions Register (BADBIR), and the German Psoriasis Registry PsoBest was used as the validation dataset. Model discrimination and calibration were assessed internally and externally using the C‐statistic, the calibration slope and the calibration in the large.ResultsOverall 175 (1·7%) out of 10 033 participants from BADBIR and 41 (1·7%) out of 2423 participants from PsoBest developed a serious infection within 1 year of therapy initiation. Selected predictors in a multiple logistic regression model included nine baseline covariates, and starting infliximab was the strongest predictor. Evaluation of model performance showed a bootstrap optimism‐corrected C‐statistic of 0·64 [95% confidence interval (CI) 0·60–0·69], calibration in the large of 0·02 (95% CI −0·14 to 0·17) and a calibration slope of 0·88 (95% CI 0·70–1·07), while external validation performance was poor, with C‐statistic 0·52 (95% CI 0·42–0·62), calibration in the large 0·06 (95% CI −0·25 to 0·37) and calibration slope 0·36 (95% CI −0·24 to 0·97).ConclusionsWe present the first results of the development of a multivariable prediction model. This model may help patients and dermatologists in the U.K. and the Republic of Ireland to identify modifiable risk factors and inform therapy choice in a shared decision‐making process.

Discrete Trajectories of Resolving and Persistent Pain in People With Rheumatoid Arthritis Despite Undergoing Treatment for Inflammation: Results From Three UK Cohorts

Rheumatoid arthritis (RA) is an example of human chronic inflammatory pain. Modern treatments suppress inflammation, yet pain remains a major problem for many people with RA. We hypothesized that discrete RA subgroups might display favorable or unfavorable pain trajectories when receiving treatment, and that baseline characteristics will predict trajectory allocation. Growth mixture modelling was used to identify discrete trajectories of Short Form-36 bodily pain scores during 3 years in 3 RA cohorts (Early RA Network (n = 683), British Society for Rheumatology Biologics Register Biologics (n = 7,090) and nonbiologics (n = 1,720) cohorts. Logistic regression compared baseline predictor variables between trajectories. The role of inflammation was examined in a subgroup analysis of people with normal levels of inflammatory markers after 3 years. The mean Short Form-36 bodily pain scores in each cohort improved but remained throughout 3 years of follow-up of >1 standard deviation worse than the UK general population average. Discrete persistent pain (59–79% of cohort participants) and resolving pain (19–27%) trajectories were identified in each cohort. In Early RA Network, a third trajectory displaying persistently low pain (23%) was also identified. In people with normal levels of inflammatory markers after 3 years, 65% were found to follow a persistent pain trajectory. When trajectories were compared, greater disability (adjusted odds ratio = 2.3–2.5 per unit baseline Health Assessment Questionnaire score) and smoking history (adjusted odds ratio = 1.6–1.8) were risk factors for persistent pain trajectories in each cohort. In conclusion, distinct trajectories indicate patient subgroups with very different pain prognosis during treatment for RA. Inflammation does not fully explain the pain trajectories, and noninflammatory factors as well as acute phase response predict which trajectory an individual will follow. Targeted treatments additional to those which suppress inflammation might reduce the long-term burden of arthritis pain. PerspectiveImmunosuppression decreases inflammation in RA, but pain outcomes are less favorable. Discrete persistent and resolving pain trajectories were identified after treatment, both in early and established RA. Smoking and greater disability at baseline predicted persistent pain. Identifying patient subgroups with a poor pain prognosis could enable adjunctive treatment to improve outcomes.

Impact of TNF inhibitor therapy on joint replacement rates in rheumatoid arthritis: a matched cohort analysis of BSRBR-RA UK registry data.

ObjectivesPrevious ecological data suggest a decline in the need for joint replacements in RA patients following the introduction of TNF inhibitor (TNFi) therapy, although patient-level data are lacking. Our primary aim was to estimate the association between TNFi use and subsequent incidence of total hip replacement (THR) and total knee replacement.MethodsA propensity score matched cohort was analysed using the British Society for Rheumatology Biologics Registry (2001–2016) for RA data. Propensity score estimates were used to match TNFi users to similar conventional synthetic DMARD users (with replacement) using a 1:1 ratio. Weighted multivariable Cox regression was used to estimate the impact of TNFi on study outcomes. Effect modification by baseline age and disease severity were investigated. Joint replacement at other sites was also analysed. An instrumental variable sensitivity analysis was also performed.ResultsThe matched analysis contained a total of 19 116 patient records. Overall, there was no significant association between TNFi use vs conventional synthetic DMARD on rates of THR (hazard ratios = 0.86 [95% CI: 0.60, 1.22]) although there was significant effect modification by age (P < 0.001). TNFi was associated with a reduction in THR among those >60 years old (hazard ratio = 0.60 [CI: 0.41, 0.87]) but not in younger patients. No significant associations were found for total knee replacement or other joint replacement.ConclusionOverall, no association was found between the use of TNFi and subsequent incidence of joint replacement. However, TNFi was associated with a 40% relative reduction in THR rates among older patients.

The Hong Kong Society of Rheumatology Biologics Registry: Updated Report (Nov 2018)

The Hong Kong Society of Rheumatology Biologics Registry: Updated Report (Nov 2018)

Rituximab Therapy in Renal Amyloidosis Secondary to Rheumatoid Arthritis.

Secondary amyloid A (AA) amyloidosis is a late and serious complication of poorly controlled, chronic inflammatory diseases. Rheumatoid arthritis (RA) patients with poorly controlled, longstanding disease and those with extra-articular manifestations are under risk for the development of AA amyloidosis. Although new drugs have proven to be significantly effective in the treatment of secondary AA amyloidosis, no treatment modality has proven to be ideal. To date, only in small case series preliminary clinical improvement have been shown with rituximab therapy for AA amyloidosis secondary to RA that is refractory to TNF-α inhibitors (TNF-i) therapy. In these case series, we assessed the efficacy and safety of rituximab therapy for patients with RA and secondary amyloidosis. Hacettepe University Biologic Registry was developed at 2005. The data of the RA patients who were prescribed a biological drug were recorded regularly. Patients with biopsy proven AA amyloidosis patients were screened. Of 1022 RA patients under biologic therapy, 0.7% patients had clinically apparent histologically confirmed amyloidosis. Four of seven patients who were prescribed rituximab at least one infusion enrolled to those case series. Two of four patients showed significant clinical improvement and one of them also had decrease in proteinuria and the other one had stable renal function and proteinuria. The main goal for the treatment of AA amyloidosis is to control the activity of the underlying disorder. In this study, we showed that rituximab may be an effective treatment in RA patients with amyloidosis who were unresponsive to conventional disease modifying anti-rheumatic drugs (DMARDs) and/or TNFi.

Identifying Persons with Axial Spondyloarthritis At Risk of Poor Work Outcome: Results from the British Society for Rheumatology Biologics Register.

First, to test the hypothesis that, among working patients with axial spondyloarthritis (axSpA), those who report issues with reduced productivity at work (presenteeism) are at higher risk of work absence (absenteeism), and patients who report absenteeism are at higher risk of subsequently leaving the workforce. Second, to identify characteristics of workers at high risk of poor work outcome. The British Society for Rheumatology Biologics Register in Ankylosing Spondylitis has recruited patients meeting Assessment of Spondyloarthritis international Society criteria for axSpA from 83 centers. Data collection involved clinical and patient-reported measures at recruitment and annually thereafter, including the Work Productivity and Activity Impairment scale. Generalized estimating equations were used to identify factors associated with poor work outcomes. Of the 1188 participants in this analysis who were working at recruitment, 79% reported some presenteeism and 19% some absenteeism in the past week owing to their axSpA. Leaving employment was most strongly associated with previous absenteeism (RR 1.02 per % increase in absenteeism, 95% CI 1.01-1.03), which itself was most strongly associated with previous presenteeism, a labor-intensive job, and peripheral joint involvement. High disease activity, fatigue, a labor-intensive job, and poorer physical function were all independently associated with future presenteeism. Clinical and patient-reported factors along with aspects of work are associated with an increased risk of axSpA patients having a poor outcome in relation to work. This study has identified modifiable factors as targets, facilitating patients with axSpA to remain productive at work.

Risk factors associated with inadequate control of disease activity in elderly patients with rheumatoid arthritis: Results from a nationwide KOrean College of Rheumatology BIOlogics (KOBIO) registry.

ObjectiveThe proportion of elderly patients with rheumatoid arthritis (RA) is continuously growing as a result of the increasing aging population. We compared disease activity between different age groups, and evaluated the clinical factors associated with high disease activity.MethodsThis cross-sectional study analyzed the data of RA patients enrolled in the Korean College of Rheumatology Biologics registry (KOBIO-RA) between 2012 and 2014. Disease activity between elderly (age ≥ 65 years) and non-elderly patients (age < 65 years) was compared, and the association of clinical factors with high disease activity was assessed using a multivariate logistic regression model.ResultsOf 1,227 patients in KOBIO-RA, 244 patients with RA were aged 65 years or over. In elderly patients, the proportion of men was higher (P = 0.012), and the duration of disease was longer (P < 0.001) compared with non-elderly patients. The elderly group showed a higher incidence of comorbidity (P < 0.001), and less use of methotrexate (P = 0.004). Assessment of disease activity using various composite measures showed a higher proportion of high disease activity in elderly patients than non-elderly patients. Longer disease duration, presence of comorbidity, and non-use of methotrexate were independently associated with high disease activity (P = 0.002, P < 0.001, and P = 0.029, respectively).ConclusionsAt enrollment of KOBIO-RA, elderly patients showed higher disease activity compared with non-elderly patients. Disease duration, use of methotrexate, and comorbidity are associated with disease activity control in Korean patients with RA.

The effect of extra-articular manifestations on tumor necrosis factor-α inhibitor treatment duration in patients with ankylosing spondylitis: nationwide data from the Korean College of Rheumatology BIOlogics (KOBIO) registry.

Tumor necrosis factor-α inhibitor (TNFi) therapy has shown to be remarkably effective for treating ankylosing spondylitis (AS); however, nearly 30% of AS patients every year either stop TNFi therapy or switch to a different TNFi due to inefficacy or adverse effects. The goal of this study was to identify predictors of TNFi treatment duration, including extra-articular manifestations, using a nationwide registry in Korea. Data obtained from the Korean College of Rheumatology Biologics (KOBIO) registry, a nationwide, multi-center database representing 58 tertiary care hospitals in Korea. Demographics, clinical features, laboratory findings, disease activity indices (BASDAI, ASDAS-ESR, ASDAS-CRP), peripheral arthritis, and extra-articular manifestations (uveitis, enthesitis, dactylitis, psoriasis, and inflammatory bowel disease) were studied in patients with AS during TNFi therapy. We also analyzed treatment duration outcomes for five TNFi agents (etanercept, infliximab, infliximab biosimilar, adalimumab, and golimumab), as well as factors associated with treatment duration, particularly in terms of extra-articular manifestations. Univariable and multivariable Cox regression analyses were performed to verify preliminary results. A total 1482 AS patients starting TNFi drug therapy between Dec. 2012 and Jan. 2017 were included. No differences in demographics, disease activity, or extra-articular manifestations were evident between continued and discontinued TNFi groups at baseline, though baseline differences were detected for gender distribution, CRP, platelet counts, and HLA-B27 positivity. During treatment period, the effects of extra-articular manifestations, including uveitis (unadjusted hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.57 to 1.48, p = 0.74), enthesitis, dactylitis, psoriasis, and inflammatory bowel disease, on TNFi treatment duration were not statistically significant. By contrast, the occurrence of peripheral arthritis was significantly associated with shorter TNFi treatment duration (unadjusted HR 2.21, 95% CI 1.66 to 2.95; adjusted HR 1.38, 95% CI 1.01 to 1.88). Among disease activity indices, higher ASDAS-ESR levels were significantly associated with shortening of the TNFi treatment duration (unadjusted HR 1.87, 95% CI 1.73 to 2.03; adjusted HR 2.23, 95% CI 2.00 to 2.63). Among TNFi drugs, golimumab had a lower discontinuation rate than that of etanercept over a 3-year follow-up period (unadjusted HR 0.46, 95% CI 0.31 to 0.68; adjusted HR 0.65, 95% CI 0.43 to 0.99). In a nationwide KOBIO registry, extra-articular manifestations, including uveitis, were not associated with TNFi treatment duration. Among clinical cofactors, the development of peripheral arthritis during TNFi therapy was associated with a higher risk of TNFi treatment discontinuance in AS patients.