Persistent Disease Activity Research Articles

Pregnancy in multiple sclerosis: from scientific aspects to practical

Background: Multiple sclerosis (MS) is a disease that affects young people of reproductive age (20-40 years old), predominantly women. Therefore, almost every patient has questions about pregnancy and breastfeeding. Family planning is one of the key issues in the choice of treatment tactics. Despite the growing number of therapeutic options for individualized treatment, it is still a question how to manage women with MS who become pregnant while taking disease-modifying drugs or want to become pregnant after starting this treatment. Conclusions: Women with MS should not be discouraged from pregnancy due to their illness. It is necessary to proactively discuss pregnancy planning with all women with MS of childbearing age. Based on available data, interferon beta and glatiramer acetate appear to be most suitable for use up until the time of confirmed pregnancy. A large amount of data (more than 1000 cases) obtained from registries shows that use of interferon beta before conception and during pregnancy suggests no evidence of increase in the rate of congenital anomalies or spontaneous abortions. For women with persistent high disease activity, pulsed immune reconstitution therapy gives additional opportunity for family planning after the last dose. The choice between available options for pulsed immune reconstitution therapy should be based on efficacy balanced against the risks.

Risk Factors of Persistently Active Disease among Filipino Children with Systemic Juvenile Idiopathic Arthritis: a 10-Year Study in a Tertiary Hospital

Background: Systemic juvenile idiopathic arthritis (SJIA) is one of the most common subtypes of arthritis among children in southeast Asia with higher progression of disease activity. Unsuccessful control of the disease may lead to long-term disability resulting in functional limitations that would affect productivity of the individual. Objective: The study determined the risk factors for persistently active disease among Filipino children aged 2 weeks to 18 years diagnosed with SJIA seen in the Section of Pediatric Rheumatology of the University of Santo Tomas Hospital (USTH) from June 2009 to June 2019. Methodology: A retrospective cohort study was done involving chart review of both clinical division and private division patients. The following parameters were determined: sex, age at diagnosis, time elapsed from symptom onset to diagnosis, joint involvement, inflammatory markers and extra-articular manifestation. Statistical analysis included frequencies, percentages and logistic regression for the risk factors of interest. Results: One hundred twenty-seven patients with SJIA who were appropriately treated for at least three years were included. Among which, 88 (69%) developed persistently active disease. Among them, 36 (41%) were diagnosed at 1-5 years old. Many were diagnosed (n=54, 61%) after five weeks. The most commonly affected joints were the wrists, knees and ankles. The most common contracture noted involved the cervical joint. Only 33 (26%) patients received biologic agents. Risk factors identified for the development of persistent disease activity were low hemoglobin levels at the time of diagnosis and after one month of treatment, elevated platelet count after a month, substantial joint count after three months and increased ESR after 6 months. Conclusion: The change or improvement of the joint count and in hemoglobin, platelet count and ESR levels after appropriate treatment may determine the risk for persistently active disease in Filipino children with SJIA.

Long-term health-related quality of life outcomes of adults with pediatric onset of frequently relapsing or steroid-dependent nephrotic syndrome.

Long-term psychosocial outcomes and health-related quality of life (HRQOL) in adults with pediatric onset of frequently relapsing or steroid-dependent idiopathic nephrotic syndrome (FRNS or SDNS) remain to be determined. In this prospective cohort study, 59 adults with pediatric onset of FRNS/SDNS and persistent active glomerular disease in adulthood completed the GEDEPAC-2 questionnaire exploring 11 well-being domains. Data were compared to the French general population (FGP) with standardized incidence ratio ([SIR]; adjusted for period, age, gender). Regression models were performed to identify predictive factors of psychosocial well-being. In 82% of cases, the questionnaire was completed while the participants (n = 59; 47 men; median age = 32years; median number of relapses = 13) were in complete remission (under specific therapy in 76% of cases). Participants had higher educational degree than in the FGP (SIR = 6.3; p < 0.01) and more frequently a managerial occupation (SIR = 3.1; p < 0.01). Social integration was acceptable with regard to marital status and experience of sexual intercourse, but experiences of discrimination were far more frequent (SIR = 12.5; p < 0.01). The SF-12 mental component summary (MCS) score was altered (Z-score = - 0.6; p < 0.01) and mean multidimensional fatigue inventory (MFI-20) global fatigue score appeared high (12). Transfer from pediatric to adult healthcare was followed by a period of discontinued care for 33% of participants. Multivariate analysis revealed a close relationship between MFI-20, physical health, and MCS. This study shows that pediatric onset FRNS and SDNS may have a long-term negative impact on mental HRQOL and highlights the impact of fatigue, which is often not adequately considered in routine care.

Outcomes of anus squamous cell carcinoma. Management of anus squamous cell carcinoma and recurrences

BackgroundLittle is known about the management of squamous cell carcinoma of the anal canal and its recurrence at a population level. The aim of this study was to draw a picture of management, recurrence and survival in squamous cell carcinoma of the anal canal. Material and methodsThe 5-year probability of recurrences was estimated using the cumulative incidence function to consider competing risks of death. Net survival was estimated and a multivariate survival analysis was performed. The study was conducted using data of the Burgundy Digestive Cancer Registry. Overall, 273 squamous cell carcinomas of the anal canal registered between 1998 and 2014 were considered. ResultsOverall, 80% of patients were treated with curative intent. Of these, 61% received chemoradiotherapy, 35% received radiotherapy and 4% received abdominoperineal resection alone. After these treatments, for cure the 5-year cumulative recurrence rate was 27% overall; it was 20% after chemoradiotherapy and 38% after radiotherapy. Five-year net survival was 71% overall; it was 81% after chemoradiotherapy and 55% after radiotherapy. Conclusions and relevanceChemoradiotherapy was highly effective in routine practice. We confirm that it is difficult to distinguish between persistent active disease and local inflammation due to radiotherapy. Squamous cell carcinoma of the anal canal recurrences remains a substantial problem, highlighting the interest of prolonged surveillance. Aggressive management of recurrences may be beneficial.

The Case | Membranous nephropathy after alemtuzumab treatment

A 36-year-old woman was referred to our department for the recent onset lower limbs edema, high-grade proteinuria, and microscopic hematuria. The patient had a history of a relapsing-remitting multiple sclerosis in 2010, initially treated by interferon, which was replaced by fingolimod in 2012 given persistent disease activity. In 2016, after 2 severe flares with only partial recovery, fingolimod was switched to alemtuzumab. Accordingly, the patient was monitored regularly for potential adverse events, including monthly measurement of serum creatinine level and urinalysis.

Therapeutic outcome of diverticular associated colitis - a retrospective single centre experience.

Diverticular associated colitis (DAC) has become increasingly appreciated as a form of inflammatory disease, localized mainly in the sigmoid, and defined as chronic inflammation of the interdiverticular mucosa with sparing of rectum, right colon and diverticula themselves. A retrospective case identification from January 2005 to December 2016 was performed. Patients with a diagnosis of DAC based on clinical, endoscopic and histological findings were enrolled. We analyzed their characteristics and response to therapy, and performed a review of literature. Out of 377 pathology reports, 37 cases of DAC were identified, with a median age of 73 years and followed during 1-13 years. Six patients (16.22%) were refractory to conservative treatment and required surgery. In three patients (8.11%) evolution to ulcerative colitis (UC) was observed. Patients were divided into four endoscopic patterns, with a more benign course for type A "crescentic fold disease" compared to the other subtypes. Patients with type B "mild to moderate ulcerative colitis-like" were at significantly higher risk of persistent disease activity or relapse (p < 0.01). DAC is a multifaceted disease and considered to be a relatively benign condition. However, a subset of patients requires surgery and/or may progress to develop UC.

The brain-gut axis, inflammatory bowel disease and bioelectronic medicine.

The hallmark of inflammatory bowel diseases (IBD) is chronic intestinal inflammation with typical onset in adolescents and young adults. An abundance of neutrophils is seen in the inflammatory lesions, but adaptive immunity is also an important player in the chronicity of the disease. There is an unmet need for new treatment options since modern medicines such as biological therapy with anti-cytokine antibodies still leave a substantial number of patients with persisting disease activity. The role of the central nervous system and its interaction with the gut in the pathophysiology of IBD have been brought to attention both in animal models and in humans after the discovery of the inflammatory reflex. The suggested control of gut immunity by the brain-gut axis represents a novel therapeutic target suitable for bioelectronic intervention. In this review, we discuss the role of the inflammatory reflex in gut inflammation and the recent advances in the treatment of IBD by intervening with the brain-gut axis through bioelectronic devices.

P131 Defining refractory disease in RA and polyarticular JIA: a systematic review

Abstract Background/Aims A systematic approach to define patients with rheumatoid arthritis (RA) or polyarticular juvenile idiopathic arthritis (PolyJIA) who do not adequately respond to treatment and experience persistent symptoms (refractory disease) is absent. The objective of the systematic review was to identify how refractory disease (or relevant terminology variations) in RA/PolyJIA is defined and establish the key components/constructs of such definitions. Methods Searches were undertaken of English language articles within six medical databases, including manual searching, from January 1998 to March 2020 (PROSPERO: CRD42019127142). Articles were included if they incorporated a definition of refractory disease, or non-response, in RA/PolyJIA, with clear components to the description (e.g. disease activity assessment specified, patient perspective, number of drugs to classify non-response). A narrative synthesis mapping of the definitions was undertaken to describe refractory disease in RA/PolyJIA and classify each component within each definition through a qualitative content analysis. Results Of 6,251 studies screened, 646 studies met the inclusion criteria; 581 reported non-response criteria and 65 reported refractory disease definitions/descriptions. From the non-response studies, 39 different components included various disease activity measures, emphasising persistent disease activity and symptoms, despite treatment with at least one bDMARD. Of the papers with clear definitions for Refractory disease, 41 components were identified and categorised into three key themes: Resistance to multiple drugs/regimes with different mechanisms of action: descriptions of drugs/regimes failed, not tolerated, discontinued/switched, by specifying name, number or class of drugs failed (range 1-8 but typically ≥2 bDMARDs) and duration of treatment, and steroid use/dependency.Persistency of physical symptoms and disease activity: range of various disease activity criteria (including not achieving remission), descriptions of other patient-reported outcomes or symptoms e.g. patient global or pain VAS, presence or absence of inflammation, disease severity including new joint activity, damage or replacements.Other contributing factors: biomechanical or degenerative drivers, adverse event, co-morbidities or extra-articular manifestations, serology (RF Status) or anti-bodies (anti-CCP) and incorrect diagnosis or not relevant treatment. The most common labels were “Refractory” (80%), of which 32.7% used the term “Refractory RA” and 13.5% stating “Refractory to (drug name/class)”. “Difficult-to-treat RA” (23.1%) and “Treatment Resistant RA” (15.4%) were the most popular from remaining terms (20%). Only the minority (16.9%) reported explicitly how their definition was generated e.g. clinical experience or statistical methods. Conclusion Refractory disease can be defined as resistance to multiple drugs/regimes with different mechanisms of action as evidenced by persistency of physical symptoms and high disease activity, including contributing factors. There is a need for a clear unifying definition as the plethora of different definitions makes both study comparisons and appropriate identification of patients difficult. Disclosure H. Chaplin: None. L. Carpenter: None. A. Raz: None. E. Nikiphorou: None. H. Lempp: None. S. Norton: None.

Fluorodeoxyglucose F 18 for the Assessment of Acute Intestinal Graft-versus-Host Disease and Prediction of Response to Immunosuppressive Therapy

Graft-versus-host disease (GVHD) is a common complication that increases morbidity and mortality after allogeneic stem cell transplantation (allo-SCT). Fluorodeoxyglucose F 18 (18F-FDG)-positron emission tomography (PET) imaging has been demonstrated to be highly informative for evaluating and mapping of intestinal GVHD. To corroborate and extend existing findings and to investigate whether glucose metabolism assessed by 18F-FDG-PET might be an effective diagnostic tool to predict corticosteroid-refractory acute GVHD and overall survival. In this retrospective analysis, 101 patients with clinically suspected acute intestinal GVHD underwent 18F-FDG-PET between June 2011 and February 2019. Seventy-four of these patients with clinically and/or histologically proven acute intestinal GVHD as well as positive 18F-FDG-PET findings were analyzed in detail to assess the predictive value of 18F-FDG-PET regarding the response to immunosuppressive therapy and survival. Quantitative PET parameters, particularly the maximum standard uptake value (SUVmax), of patients with a fast response (ie, clinical improvement and decreased GVHD activity by at least 1 stage after 1 week of GVHD treatment) or slow/no response (ie, persistent disease activity for more than 1 week or increasing GVHD activity following first-line immunosuppressive therapy) were evaluated. 18F-FDG-PET detected intestinal GVHD with a sensitivity of 93% (95% confidence interval [CI], 85% to 97%) and specificity of 73% (95% CI, 45% to 91%). Patients with a fast response to immunosuppressive therapy had a mean SUVmax of 13.7 (95% CI, 11.0 to 16.5) compared with 7.6 (95% CI, 7.0 to 8.3; P=.005) observed in patients with prolonged or no response. The median overall survival (OS) was 573.0 days (95% CI, 539.5 to 606.5 days) for patients with fast response versus 255 days (95% CI, 161.0 to 349.0 days; P=.009) for patients with slow or no responses. A SUVmax threshold >8.95 applied to 18F-FDG-PET performed within 100 days after transplantation identified patients with a median OS of 390 versus 117 days for patients with SUVmax ≤8.95 (P=.036). SUVmax threshold and donor type were independent factors for OS. Our results indicate that 18F-FDG-PET is highly accurate in identifying patients with acute intestinal GVHD and may predict responses to immunosuppressive therapy as well as survival, particularly when applied within the first 100 days after transplantation. These results provide a strong rationale to integrate PET imaging in future prospective trials evaluating new therapies for acute GVHD.

Accuracy of the highly sensitive C-reactive protein/albumin ratio to determine disease activity in inflammatory bowel disease.

Persistent disease activity is associated with a poor prognosis in patients with inflammatory bowel disease (IBD). This study aims to explore the accuracy of the highly sensitive C-reactive protein/albumin ratio (CAR) in determining IBD activity.The clinical data of 231 IBD patients treated at Peking Union Medical College Hospital from 2012 to 2018 were analyzed retrospectively. The patients were classified as having active disease or remission according to the Crohn disease activity index scores for patients with Crohn disease (CD) and partial Mayo scores for patients with ulcerative colitis (UC).This study included 231 IBD patients (137 CD and 94 UC). From these groups, 182 patients had active disease, while 49 patients were in remission. The platelet counts, erythrocyte sedimentation rates, high-sensitivity C-reactive protein levels, and CAR scores were significantly higher, while hemoglobin levels, ALB, and body mass indexes were significantly lower in patients with active disease (P < 0.01). The hsCRP, CAR, and ALB significantly correlated with disease activity for both CD and UC (P < 0.001). The area under the curve (AUC) of CAR was highest among the laboratory indexes at 0.829, and the AUC of CAR in the UC patients was larger than that of the CD patients. Also, CAR with cutoff value of 0.06 displayed the highest sensitivity among the indexes for IBD activity at 83.05%.CAR is a useful biomarker for identifying disease activity in patients with CD and UC. Higher CAR levels are indicative of increased IBD activity. CAR may be more valuable in UC than that in CD for assessing the degree of IBD activity.

Recurrence of disease activity after fingolimod discontinuation in older patients previously stable on treatment

BackgroundDiscontinuing fingolimod (FTY) in older patients is a growing concern with little evidence supporting the decision to pursue treatment and reasonable doubt for disease reactivation after withdrawal. ObjectiveTo estimate the incidence of recurrence of disease activity (RDA) and rebound after FTY withdrawal in patients older than 50 years. MethodsRetrospective analysis of all MS patients in our clinic who discontinued FTY after at least 6 months of treatment, according to disease activity on FTY and age at discontinuation. RDA was defined as the occurrence of either clinical and/or MRI activity in the 6 months after FTY withdrawal and rebound when the levels of disease activity surpassed pretreatment activity. ResultsFrom the 128 patients who discontinued FTY since 2011, up to 35.2% of patients experienced evidence of disease activity and 12.5% had a rebound. The incidence of both RDA and rebound was not different among individuals who had persistent disease activity on FTY to those who stopped FTY for other reasons than inefficacy (RDA: 25.5% vs 20.5%, p = 0.353 rebound: 14.5% vs 11%, p = 0.596). Negative predictive factors for RDA were younger age at disease onset (p = 0.036), highly active disease at baseline (p = 0.003) and previous treatment with NTZ (p = 0.013). Older age at FTY discontinuation did not reduce the risk of RDA in patients previously stable on treatment (OR 0.972, 95% CI 0.871–1.085, p = 0.613), although the incidence of RDA/rebound was half less in the older patients (36.5% in the <50 vs 19% in the ≥50 year-old, p = 0.174) and none of the patients over 60 experienced RDA. ConclusionAlthough there is a tendency for a lower risk of disease reactivation in the older patients, the incidence of RDA, and even rebound, is not negligible between the age of 50 and 60 years, even in patients with previously stable MS on FTY.

Summarizing current refractory disease definitions in rheumatoid arthritis and polyarticular juvenile idiopathic arthritis: systematic review.

ObjectivesTo identify how refractory disease (or relevant terminology variations) in RA and polyarticular JIA (polyJIA) is defined and establish the key components of such definitions.MethodsSearches were undertaken of English-language articles within six medical databases, including manual searching, from January 1998 to March 2020 (PROSPERO: CRD42019127142). Articles were included if they incorporated a definition of refractory disease, or non-response, in RA/polyJIA, with clear components to the description. Qualitative content analysis was undertaken to describe refractory disease in RA/polyJIA and classify each component within each definition.ResultsOf 6251 studies screened, 646 met the inclusion criteria; 581 of these applied non-response criteria while 65 provided refractory disease definitions/descriptions. From the non-response studies, 39 different components included various disease activity measures, emphasizing persistent disease activity and symptoms, despite treatment with one or more biologic DMARD (bDMARD). From papers with clear definitions for refractory disease, 41 components were identified and categorized into three key themes: resistance to multiple drugs with different mechanisms of action, typically two or more bDMARDs; persistence of symptoms and disease activity; and other contributing factors. The most common term used was ‘refractory’ (80%), while only 16.9% reported explicitly how their definition was generated (e.g. clinical experience or statistical methods).ConclusionRefractory disease is defined as resistance to multiple drugs with different mechanisms of action by persistence of physical symptoms and high disease activity, including contributing factors. A clear unifying definition needs implementing, as the plethora of different definitions makes study comparisons and appropriate identification of patients difficult.

High infliximab trough concentrations are associated with sustained histologic remission in inflammatory bowel disease: a prospective cohort study

BackgroundThe threshold concentration of infliximab during maintenance therapy has not been well-defined in relation to histologic remission. The aim of the study is to dentify the maintenance-phase infliximab concentration associated with histologic remission in inflammatory bowel disease patients (IBD).MethodsA prospective cohort study was carried out in 104 IBD patients seen at a tertiary care centre in London, Canada. Infliximab trough concentrations were collected during the maintenance phase of treatment and compared between participants with and without evidence of histologic remission. Participants were additionally evaluated for sustained histologic remission, and relapse to active disease.ResultsParticipants in histologic remission attained higher mean concentrations of infliximab during the maintenance phase (10.34 ± 0.69 μg/ml) compared to those with persistent disease activity (6.23 ± 0.67 μg/ml, p-value < 0.0001). Additionally, during the maintenance phase, sustained histologic remission was also associated with a higher mean concentration of infliximab (10.81 ± 5.46 μg/ml) compared to those who relapsed to active disease (5.68 ± 3.70, p < 0.001). Overall, participants with a mean infliximab trough concentration greater than 8ug/ml were more likely to have histologic remission (area under the receiver operating characteristic curve, AUROC = 0.72, 95%CI = 0.65–0.84, p < 0.0001) and sustained histologic remission (AUC = 0.77, 95%CI = 0.63–0.91, p = 0.002).ConclusionMaintenance-phase infliximab trough concentrations greater than 8 μg/ml, which is higher than the currently recommended target concentration, are highly associated with histologic remission and sustained histologic remission.

Treatment of Calcinosis in Juvenile Dermatomyositis.

Juvenile dermatomyositis (JDM) is a rare autoimmune disease characterised by muscle and skin involvement. Calcinosis is a debilitating complication of JDM which is difficult to treat and may cause long-term morbidity. The purpose of this review is to provide an update for the treatment of JDM-associated calcinosis based on previously published studies. Evidence-based studies are lacking for the management of calcinosis, and current treatment modalities have been largely based on case reports, case series, cohort studies, limited controlled studies and anecdotal clinical experience. The use of early aggressive therapy for resistant cases is strongly suggested to halt persistent disease activity which may help in reducing steroid use and their associated complications. Recent insights into disease pathogenesis, myositis-specific antibodies and genetic associations have led to identification of novel therapeutic targets such as Janus kinase (JAK) 1/2. Different treatment regimens with variable outcomes are in use for the treatment of refractory calcinosis; nevertheless, the level of evidence is not sufficient to propose specific guidelines. Recently, JAK 1/2 inhibitors have shown to be effective as an emerging therapeutic option highlighting that translational and clinical research is crucial to develop targeted treatment for JDM-associated calcinosis.

Total plaque area and plaque echogenicity are novel measures of subclinical atherosclerosis in patients with systemic lupus erythematosus.

Patients with SLE have an increased risk of developing cardiovascular disease (CVD). Multiple studies have shown that these patients have increased numbers of carotid plaques and greater intima-media thickness (IMT) than healthy controls. Measures such as total plaque area (TPA) and plaque echogenicity may be more sensitive and more relevant to cardiovascular risk than presence of plaque and IMT alone. Our objective was to produce the first report of TPA and echogenicity in a population of patients with SLE. One hundred patients with SLE and no history of clinical CVD were recruited. Clinical, serological and treatment variables were recorded and serum was tested for antibodies to apolipoprotein A-1 and high-density lipoprotein. Both carotid and both femoral artery bifurcations of each patient were scanned to determine IMT, TPA and echogenicity of plaques. Univariable and multivariable statistical analyses were carried out to define factors associated with each of these outcomes. Thirty-six patients had carotid and/or femoral plaque. Increasing age was associated with presence of plaque and increased IMT. Triglyceride levels were associated with presence of plaque. Mean (s.d.) TPA was 60.8 (41.6) mm2. Patients taking prednisolone had higher TPA. Most plaques were echolucent, but increased echogenicity was associated with prednisolone therapy and persistent disease activity. TPA and plaque echogenicity in patients with SLE are associated with different factors than those associated with presence of plaque and IMT. Longitudinal studies may show whether these outcome measures add value in the management of cardiovascular risk in SLE.

The changing states of fibromyalgia in patients with axial spondyloarthritis: results from the British Society of Rheumatology Biologics Register for Ankylosing Spondylitis.

ObjectivesTo identify factors associated with FM development and recovery in patients with axial SpA (axSpA).MethodsThe British Society of Rheumatology Biologics Register for Ankylosing Spondylitis (BSRBR-AS) recruited patients with axSpA from 83 centres in a prospective study. FM was diagnosed using the self-reported Fibromyalgia Survey Diagnostic Criteria from 2015. Measures of axSpA disease activity and clinical findings were recorded at regular intervals. We identified predictors for FM development and recovery between yearly visits using uni- and multivariable logistic regression models.ResultsA total of 801 participants, 247 (30.8%) female, had two or more visits and were eligible for inclusion. A total of 686 participants did not have FM at baseline, of whom 45 had developed FM at follow-up, while 115 participants had FM at baseline, of whom 77 had recovered at follow-up. A high baseline BASDAI score [odds ratio (OR) 1.27 (95% CI 1.08, 1.49)] and Widespread Pain Index (WPI) [OR 1.14 (95% CI 1.02, 1.28)] were significantly associated with FM development in the final multivariable model. A low baseline BASFI score [OR 0.68 (95% CI 0.53, 0.86)] and WPI [OR 0.84 (95% CI 0.720, 0.97)] and starting a TNF inhibitor [OR 3.86 (95% CI 1.54, 9.71)] were significantly associated with FM recovery.ConclusionHigh levels of disease activity and the presence of widespread pain is associated with the development of FM in patients with axSpA, while low levels of the same variables and starting a TNF inhibitor are associated with recovery from FM. The presence of comorbid FM should be considered in patients with persistent high axSpA disease activity and widespread pain.

IL-23 skin and joint profiling in psoriatic arthritis: novel perspectives in understanding clinical responses to IL-23 inhibitors

ObjectivesTo determine the relationship between synovial versus skin transcriptional/histological profiles in patients with active psoriatic arthritis (PsA) and explore mechanistic links between diseased tissue pathology and clinical outcomes.MethodsTwenty-seven active PsA...

Efficacy of leflunomide in the treatment of vasculitis.

Only a few small case series, case reports, and one small clinical trial suggested some benefit of leflunomide (LEF) in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis and other vasculitides. We analysed the clinical efficacy and tolerability of LEF in a large cohort of patients with various vasculitides. This was a retrospective analysis of patients who received LEF for treatment of their vasculitis enrolled in the Vasculitis Clinical Research Consortium (VCRC) Longitudinal Study and in 3 additional centres from the Canadian vasculitis research network (CanVasc). Data for 93 patients were analysed: 45 had granulomatosis with polyangiitis (GPA), 8 microscopic polyangiitis (MPA), 12 eosinophilic granulomatosis with polyangiitis (EGPA), 14 giant-cell arteritis (GCA), 9 Takayasu's arteritis (TAK), and 5 polyarteritis nodosa (PAN). The main reason for initiation of LEF was active disease (89%). LEF was efficacious for remission induction or maintenance at 6 months for 62 (67%) patients (64% with GCA, 89% with TAK, 80% with PAN, 69% with GPA, 75% with MPA, 33% with EGPA); 20% discontinued LEF before achieving remission because of persistent disease activity. Overall, 22 adverse events (gastrointestinal symptoms being the most common) led to drug discontinuation in 18 (19%) patients, of which 12 stopped LEF before month 6, before showing any benefit in 8/12 of these patients. Leflunomide can be an effective therapeutic option for various vasculitides, especially for non-severe refractory or relapsing ANCA-associated vasculitis or large-vessel vasculitis. No new safety signals for LEF were identified in this population.

Successful Treatment of Refractory Ulcerative Proctitis in a Pediatric Patient Using Topical Tacrolimus

Successful Treatment of Refractory Ulcerative Proctitis in a Pediatric Patient Using Topical Tacrolimus

Factors associated with disability in patients with rheumatoid arthritis with persistent moderate disease activity: a retrospective cohort study

BackgroundMany patients with rheumatoid arthritis (RA) do not attain remission/low disease activity, remaining in a moderate disease activity state (MDAS) with ongoing disability and impaired quality of life (QoL). If patients in persistent MDAS with poor future outcomes could be prospectively identified, they could arguably be treated more intensively. We evaluated baseline factors predicting function (Health Assessment Questionnaire-Disability Index [HAQ-DI] scores) and QoL (3-level EuroQol-5 dimensions questionnaire [EQ-5D-3L] index scores) at 12 months in patients with RA in persistent MDAS in a real-world setting.MethodsPatients with persistent MDAS (Disease Activity Score for 28-joint count based on erythrocyte sedimentation rate [DAS28-ESR] 3.2–5.1 on at least two consecutive outpatient appointments over 12 months) were identified retrospectively from Guy’s Hospital RA Centre and analysed in two groups: (1) biologic naïve at baseline or (2) receiving/ever received biologics. The baseline timepoint was the second-visit MDAS DAS28-ESR score; the endpoint was the closest visit to 12 months. Linear regression analyses evaluated relationships between baseline variables and (1) 12-month HAQ-DI scores, (2) 12-month rank-transformed EQ-5D-3L index scores, (3) 12-month changes in HAQ-DI scores, and (4) 12-month changes in EQ-5D-3L index scores.ResultsThe analysis included 207 biologic-naïve and 188 biologic-experienced patients. All patients had moderate disability (mean HAQ-DI 1.21 and 1.46) and impaired QoL (mean EQ-5D-3L index scores 0.52 and 0.50). Many reported moderate/severe pain (93 and 96%) and showed little change in HAQ-DI and EQ-5D-3L index scores over 12 months. In both biologic-naïve and biologic-experienced groups, multivariate analysis revealed a significant association between baseline HAQ-DI scores and endpoint HAQ-DI scores (β = 0.67, P < 0.001 and β = 0.76, P < 0.001, respectively), 12-month changes in HAQ-DI scores (both β = − 0.21, P < 0.001), and 12-month EQ-5D-3L index scores (β = − 0.57, P < 0.001 and β = − 0.29, P = 0.004, respectively). Baseline EQ-5D-3L index scores were significantly associated with 12-month changes in EQ-5D-3L index scores in both groups (β = − 0.73, P < 0.001 and β = − 0.40, P = 0.003, respectively).ConclusionsPatients with RA in persistent MDAS experience substantial ongoing physical disability, poor QoL, and pain. HAQ-DI is an important predictor of future disability and reduced QoL, supporting current national recommendations to measure HAQ-DI in routine care.