Persistent Disease Activity Research Articles

Association of pre- and postoperative αKlotho levels with long-term remission after pituitary surgery for acromegaly

Soluble αKlotho (sKl) is a disease-specific biomarker that is elevated in patients with acromegaly and declines after surgery for pituitary adenoma. Approximately 25% of patients do not achieve remission after surgery, therefore a risk stratification for patients early in the course of their disease may allow for the identification of patients requiring adjuvant treatment. Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) have been assessed as biomarker for disease activity, however the value of sKl as a predictive biomarker of surgical success has not been evaluated yet. In this study, we measured serum biomarkers before and after transsphenoidal pituitary surgery in 55 treatment-naïve patients. Based on biochemical findings at follow-up (7–16 years), we divided patients into three groups: (A) long-term cure (defined by normal IGF-1 and random low GH (< 1 μg/l) or a suppressed GH nadir (< 0.4/μg/l) on oral glucose testing); (B) initial remission with later disease activity; (C) persistent clinical and/or biochemical disease activity. sKl levels positively related to GH, IGF-1 levels and tumor volume. Interestingly, there was a statistically significant difference in pre- and postoperative levels of sKl between the long-term cure group and the group with persistent disease activity. This study provides first evidence that sKl may serve as an additional marker for surgical success, decreasing substantially in all patients with initial clinical remission while remaining high after surgery in patients with persistent disease activity.

Automatic quantification of retinal photoreceptor integrity to predict persistent disease activity in neovascular age-related macular degeneration using deep learning.

Using deep learning (DL)-based technique, we identify risk factors and create a prediction model for refractory neovascular age-related macular degeneration (nAMD) characterized by persistent disease activity (PDA) in spectral domain optical coherence tomography (SD-OCT) images. A total of 671 typical B-scans were collected from 186 eyes of 186 patients with nAMD. Spectral domain optical coherence tomography images were analyzed using a classification convolutional neural network (CNN) and a fully convolutional network (FCN) algorithm to extract six features involved in nAMD, including ellipsoid zone (EZ), external limiting membrane (ELM), intraretinal fluid (IRF), subretinal fluid (SRF), pigment epithelium detachment (PED), and subretinal hyperreflective material (SHRM). Random forest models were probed to predict 1-year disease activity (stable, PDA, and cured) based on the quantitative features computed from automated segmentation and evaluated with cross-validation. The algorithm to segment six SD-OCT features achieved the mean accuracy of 0.930 (95% CI: 0.916-0.943), dice coefficients of 0.873 (95% CI: 0.847-0.899), a sensitivity of 0.873 (95% CI: 0.844-0.910), and a specificity of 0.922 (95% CI: 0.905-0.940). The six-metric model including EZ and ELM achieved the optimal performance to predict 1-year disease activity, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.980, the accuracy of 0.930, the sensitivity of 0.920, and the specificity of 0.962. The integrity of EZ and ELM significantly improved the performance of the six-metric model than that of the four-metric model. The prediction model reveals the potential to predict PDA in nAMD eyes. The integrity of EZ and ELM constituted the strongest predictive factor for PDA in nAMD eyes in real-world clinical practice. The results of this study are a significant step toward image-guided prediction of long-term disease activity in the management of nAMD and highlight the importance of the automatic identification of photoreceptor layers.

Chronic recurrent multifocal osteomyelitis and tofacitinib: a case series.

Dear Editor, Chronic recurrent multifocal osteomyelitis (CRMO), an inflammatory bone disease of unclear aetiology, affects primarily children and can lead to persistent bone pain and bone destruction. Treatments for CRMO refractory to NSAIDs include non-biologic DMARDs, TNF-α inhibitors (TNFis) or bisphosphonates [1–6]. However, novel therapies are needed for children with severe CRMO. Tofacitinib, an oral janus kinase inhibitor, is approved for PsA and ulcerative colitis. It has been shown to improve enthesitis, dactylitis, and radiographic progression [7]. This case series presents four patients with CRMO who were treated with tofacitinib. Ethics approval IRB#1232 was obtained for this study, and informed consent was received from the patients. The clinical characteristics and treatments of the patients are summarized in Table 1. A white girl with psoriasis since age 4 that failed MTX and etanercept treatment presented at 9 years of age with several months of worsening hand, elbow and knee pain. She underwent bone biopsy after confirmation of multifocal osteomyelitis by MRI and subsequently was diagnosed with CRMO. She was started on meloxicam and transitioned to infliximab and MTX. Her CRMO was well controlled, but her psoriasis flared after 9 months. She received a series of biologics, including golimumab then adalimumab, which caused worsening of the psoriasis, for which ustekinumab was added for 6 months. All biologics were discontinued 20 months after diagnosis and the girl received pamidronate for 21 months for her CRMO. Due to the persistent active bone disease and poorly controlled psoriasis (despite topical treatment, UV therapy and CSA), she was transitioned to tofacitinib 4 years after initial diagnosis, with improvement in CRMO on MRI. At her most recent visit 7 months after Xeljanz initiation, she had no bone pain or swelling, stable psoriasis, and her MRI showed minimally active disease.

Age differential response to bevacizumab therapy in choroidal neovascularization in rabbits

Choroidal neovascularization (CNV) in young rabbits has been shown to have a rapid, robust response after treatment with bevacizumab, an anti-vascular endothelial growth factor (VEGF) medication. This investigation evaluates an age differential response to bevacizumab in older populations of rabbits using multimodal high resolution molecular imaging. Young (4 months old) and life span (14 months old) rabbits were given subretinal injections of Matrigel and VEGF to produce CNV. All CNV rabbit models were then treated with a bevacizumab intravitreal injection. Rabbits were then monitored longitudinally using photoacoustic microscopy (PAM), optical coherence tomography (OCT), color photography, and fluorescence imaging. Chain-like gold nanoparticle clusters (CGNP) conjugated with tripeptide arginylglycylaspartic acid (RGD) was injected intravenously for molecular imaging. Robust CNV developed in both young and old rabbits. After intravitreal bevacizumab injection, fluorescence signals were markedly decreased 90.13% in the young group. In contrast, old rabbit CNV area decreased by only 10.56% post-bevacizumab treatment. OCT images confirmed a rapid decrease of CNV in the young group. CGNPs demonstrated high PAM signal in old rabbits and minimal PAM signal in young rabbits after bevacizumab, indicating CNV regression. There is a significant difference in response to intravitreal bevacizumab treatment between young and old rabbits with CNV which can be monitored with multimodal molecular imaging. Old rabbits demonstrate significant persistent disease activity. This represents the first large eye model of persistent disease activity of CNV and could serve as the foundation for future investigations into the mechanism of persistent disease activity and the development of novel therapies.

Effectiveness and baseline predictive factors for Tofacitinib response in rheumatoid arthritis in a real-world setting: A national multicenter study

Background: Evidence of effectiveness and safety of tofacitinib (TOF) in the real-world setting in Latin America is currently limited and crucial to complement long-term extension data from randomized controlled trials. Methods: Patients initiated on TOF between 2014 and 2020 with RA (ACR/EULAR, 2010 criteria) were analyzed. The primary end point at month 3 was remission measured by DAS28-ESR. Secondary end points included prognostic factors for remission at 3 months and of monotherapy at month 12. Results: Overall, 134 RA patients were analyzed. Remission was achieved in 38.06% at month 3. In univariate analysis, persistent disease activity at 3 months was observed in those patients with longer duration of disease, structural radiological damage, higher baseline DAS28-ESR and greater frequency in previous use of bDMARD. In multivariate analysis, previous use of bDMARD was significantly associated with a decrease in the probability of remission at 3 months. At 12 months, TOF monotherapy group was elderly (p = 0.009) and had a trend for lower frequency of anti-CCP. Treatment persistence was 94.78% at 3 months, 82.84% at 6 months and 66.42% at 12 months. Conclusions: Clinical remission at 3 months was negatively associated with prior bDMARD and poor prognostic factors. TOF monotherapy at 12 months was more common in elderly patients.

POS0266 EFFECTIVENESS OF A SPACING-UP STRATEGY AFTER ONE-YEAR COURSE OF WEEKLY TOCILIZUMAB IN PATIENTS WITH GIANT CELL ARTERITIS: A SINGLE-CENTRE PROSPECTIVE STUDY

BackgroundAlthough tocilizumab (TCZ) is extensively used for the treatment of giant cell arteritis (GCA), there is still uncertainty with regard to optimal treatment duration. The GiACTA open-label extension phase showed that 58% of patients treated with a 12-month course of weekly TCZ had a disease flare in the 2 years following therapy suspension1, suggesting that some patients may need a more prolonged duration of this therapy.ObjectivesTo evaluate efficacy and safety of low-dose TCZ maintenance in GCA patients who achieved remission after one year of standard TCZ therapy.MethodsGCA patients eligible for TCZ according to the 2018 EULAR recommendations2 and who achieved remission after one year of weekly subcutaneous TCZ were prospectively enrolled. TCZ was administered every-other-week (EOW) for additional 12 months, and eventually suspended. Patients were evaluated 4-monthly during TCZ therapy, and 1 and 6 months after TCZ suspension (Figure 1). In patients with large-vessel (LV) involvement at baseline, PET scan was performed 12 and 24 months after TCZ start. Primary outcome was relapse-free survival at month 6 since TCZ suspension. Relapse-free survival during TCZ therapy and imaging response at PET scan were also evaluated. Adverse events were recorded.Figure 1.Study design.Results17 patients were enrolled (12 women, 71%; mean age 71.5±8.7 years). Disease features at diagnosis and TCZ start are listed in Table 1. Reasons for TCZ start were clinical or imaging disease flare (n=9), persistence of disease activity (n=5), and steroid-related adverse events (n=3). At TCZ start, median disease duration was 8 (3-22) months, serum C-reactive protein (CRP) was 13 (6-22) mg/L, daily prednisone (PDN) dose was 25 (15-37.5) mg; 4 patients were already on methotrexate (MTX) which was maintained in 1 of them; 10 patients (59%) had LV involvement on PET scan. At TCZ EOW start, no patient was on PDN and 1 patient was on MTX; MTX was added in another patient due to persistence of LV involvement at PET scan. All patients completed the 24-month TCZ course. Two patients (12%) had a polymyalgic flare while on EOW TCZ: one patient at month 1 and one patient at month 6; of note, one of them had a polymyalgic flare also while on weekly TCZ. Both flares were managed with a PDN course with complete clinical remission. No patient had active LV involvement at 24-month PET scan. Adverse events on EOW TCZ were zoster reactivation (n=1) and neutropenia (n=1). At TCZ stop, no patient was on PDN and 2 patients were on MTX. One month after TCZ stop, all patients were in remission. Six months after TCZ stop, 4 patients (24%) experienced a flare, which was successfully managed in all cases with TCZ weekly re-introduction; in 2 patients, a PDN course was also started.Table 1.Patients’ characteristics at giant cell arteritis diagnosis and at study entry.GCA diagnosis, n=17n (%)TCZ start, n=17n (%)Headache16 (94)5 (29)Scalp tenderness11 (65)5 (29)Jaw claudication9 (53)2 (12)Ocular ischemic manifestations3 (17)0 (0)Polymyalgia rheumatica8 (47)0 (0)Constitutional symptoms14 (82)7 (47)Active vasculitis on PET10 (59)10 (59)Modality of diagnosisVascular ultrasound7 (47)-Temporal artery biopsy3 (17)-PET10 (59)10 (59)ConclusionIn this proof-of-concept study, low-dose TCZ maintenance in GCA showed excellent disease control, which was maintained in most patients after therapy suspension. Longer follow-up and replication in larger cohorts are required.

Physician Global Assessment as a Disease Activity Measure for Relapsing Polychondritis.

Relapsing polychondritis (RP) is a systemic inflammatory disorder of cartilage that lacks validated disease activity measures. Our objective was to test physician global assessment (PhGA), a measure of disease activity commonly used in rheumatic diseases, in a cohort of patients with RP, which has not been done before. Adult patients in an observational cohort of RP underwent standardized, comprehensive evaluation at approximately 6-month intervals. PhGA was scored by 3 physicians from the evaluating institution on a scale of 0-10 for each visit. A random subset of 20 visits was scored by 3 independent physicians not affiliated with the evaluating institution. Treatment change between consecutive visits was categorized as increased, decreased, or unchanged. In total, 78 patients were evaluated over 164 visits. The intraclass correlation coefficient (ICC2,1 ) for the 3 raters from the evaluating institution was excellent (0.79 [95% confidence interval (95% CI) 0.73, 0.84]) but was poor in the subset of cases scored by the additional raters (ICC2,1 0.27 [95% CI -0.01, 0.53]). Median PhGA was 3 (range 0-7). PhGA weakly correlated with C-reactive protein level (rs = 0.30, P < 0.01). In response to increased treatment, median PhGA decreased from 3 (interquartile range [IQR] 2, 4) to 2 (IQR 2, 3) (P < 0.01) but rarely went to 0. Within a single center, PhGA can be used to quantify disease activity and monitor disease response in RP. Persistent disease activity despite treatment, rather than a relapsing-remitting pattern, is observed for most patients with RP. Reliability of PhGA may not generalize across different institutions. A validated disease-specific activity index is needed in RP.

P044 Giant cell arteritis in an immunocompromised patient with rheumatoid arthritis

Abstract Background/Aims Giant cell arteritis (GCA) is a common medium-large vessel vasculitis with an approximate incidence of 10 cases per 100,000 people over 50 years old. First line management of GCA is with high dose glucocorticoids followed by steroid sparing agents, namely methotrexate with tocilizumab for resistant cases. Here we describe a patient established on methotrexate for rheumatoid arthritis, receiving rituximab with intravenous methylprednisolone (IVMP) who went on to develop GCA. Methods A 65-year-old Caucasian female with seropositive rheumatoid arthritis (RA) established on 20mg weekly subcutaneous methotrexate and low dose 5mg prednisolone was escalated to her tenth cycle of rituximab with 100mg IVMP for an arthritic flare. The day after her second infusion, two weeks apart, the patient presented with headaches. These were severe temporal pains with scalp tenderness for the past four weeks. She denied visual changes, jaw claudication or polymyalgia rheumatica features. Examination identified bilateral thickened and tender temporal arteries. Ultrasound confirmed bilateral frontal temporal artery halo signs, with intimal thickening of 0.9mm and 0.4mm of the left and right respectively. Blood tests showed a rise in C-reactive protein to 46mg/L from 13mg/L. In view of these findings, procedural risks and recent immunosuppression biopsy was not sought. The patient was commenced on 40mg prednisolone before weaning by 5 mg 2-3 weekly. Her headache improved, without relapse and her CRP normalised within 2 weeks. Given tocilizumab had previously been ineffective in the patient’s RA management, she declined transition to this biologic and her methotrexate was increased to 25mg. Results Development of GCA in a patient with pre-established immunotherapy is rare. This report represents only the second case noted in the literature of the vasculitis occurring in a patient whilst on rituximab. Excluding tocilizumab (anti-IL6), a meta-analysis of other biological agents including infliximab, adalimumab, etanercept (anti-TNF) and abatacept (anti-CTLA4) have not been proven to have clinical significance over placebo in GCA. However, evidence of rituximab and its role in GCA is limited with no clinical trials. Contrary to this case of GCA, rituximab (anti-CD20) therapy has a well-recognised role in ANCA associated vasculitis and there are growing calls for trials in large vessel vasculitides. Recent case series of rituximab in Takayasu’s arteritis have presented contrasting outcomes of persistent disease activity versus clinical and laboratory remission. Robust clinical trials are therefore required to evaluate the long-term impact of rituximab on large vessel vasculitis. Conclusion Although rare, clinicians should be vigilant for the development of GCA despite established immunosuppression. Disclosure N. Chauhan: None. A. Kinder: None.

Initial experience in treating polypoidal choroidal vasculopathy with brolucizumab in Indian eyes - A multicenter retrospective study.

Purpose:To report the initial experience of managing treatment-resistant and treatment-naïve eyes with polypoidal choroidal vasculopathy (PCV) by using brolucizumab 6 mg.Methods:This was a retrospective multicentric series of all consecutive eyes with PCV treated with brolucizumab. Treatment resistance was defined as taking at least six prior anti-VEGF injections over the past 1 year and showing persistent disease activity in the form of intra (IRF) or subretinal fluid (SRF) or both. All patients were treated on a pro re nata (PRN) basis and followed up monthly. Retreatment was considered when either SRF or IRF were present at any time point during the study.Results:We included 21 eyes of 21 patients with PCV with a mean age of 65.1 ± 9.9 years, of which 16 eyes (76%) were treatment-resistant. The mean follow-up period from receiving the first brolucizumab was 27.3 ± 3.3 weeks. Of the 21 eyes, seven eyes (33%) received three injections during follow-up, 13 eyes (62%) received two injections, and one eye received one injection. The mean injection-free interval was 12 ± 1.2 weeks. The median pretreatment vision was 0.6 logMAR (IQR = 0.47–1 logMAR) and improved to 0.3 logMAR (IQR = 0.25–0.6 logMAR), whereas the mean macular thickness improved from 443 ± 60 mm at baseline to 289 ± 25 mm (P < 0.001) at the last follow-up period. None of the eyes experienced any intraocular inflammation across 48 injection sessionsConclusion:Brolucizumab is safe and effective in controlling PCV disease in both treatment-resistant and treatment-naïve eyes.

The Diversity of Serum Anti-DSG3 IgG Subclasses Has a Major Impact on Pemphigus Activity and Is Predictive of Relapses After Treatment With Rituximab.

IntroductionWe studied the distribution and in vitro pathogenicity of anti-DSG3 IgG subclasses during the course of pemphigus vulgaris (PV).MethodsWe longitudinally studied the distribution of anti-DSG3 IgG subclasses (before versus after treatment) in sera from PV patients, using an addressable-laser bead immunoassay (ALBIA). The in vitro pathogenicity of corresponding sera was tested using keratinocyte dissociation and immunofluorescence assays.ResultsSixty-five sera were assessed at baseline (33 from patients treated with rituximab and 32 with corticosteroids). Sixty-three percent of these baseline sera contained 2 or more anti-DSG3 IgG subclasses versus 35.7% of sera from patients in complete remission (CR) and 75.0% of sera from patients with persistent disease activity after treatment. IgG4 was the most frequently detected anti-DSG3 IgG subclass, both in patients with disease activity and in those in CR. The presence of three or more anti-DSG3 IgG subclasses was predictive of relapse, in particular when it included IgG3, with a positive predictive value of 62.5% and a negative predictive value of 92%. While anti-DSG3 IgG4 Abs from sera collected before treatment were most often pathogenic, anti-DSG3 IgG4 from sera collected after treatment were pathogenic only after adjusting their titer to the one measured before treatment. The IgG3 fraction containing anti-DSG3 Abs also had an in vitro pathogenic effect. The disappearance of the pathogenic effect of some sera after removal of anti-DSG3 IgG3 suggested an additional effect of this IgG subclass.ConclusionThe serum levels and number of anti-DSG3 IgG subclasses drive the pathogenic effect of pemphigus sera and may predict the occurrence of relapses.

Social determinants of health influence disease activity and functional disability in Polyarticular Juvenile Idiopathic Arthritis

BackgroundSocial determinants of health (SDH) greatly influence outcomes during the first year of treatment in rheumatoid arthritis, a disease similar to polyarticular juvenile idiopathic arthritis (pJIA). We investigated the correlation of community poverty level and other SDH with the persistence of moderate to severe disease activity and functional disability over the first year of treatment in pJIA patients enrolled in the Childhood Arthritis and Rheumatology Research Alliance Registry.MethodsIn this cohort study, unadjusted and adjusted generalized linear mixed effects models analyzed the effect of community poverty and other SDH on disease activity, using the clinical Juvenile Arthritis Disease Activity Score-10, and disability, using the Child Health Assessment Questionnaire, measured at baseline, 6, and 12 months.ResultsOne thousand six hundred eighty-four patients were identified. High community poverty (≥20% living below the federal poverty level) was associated with increased odds of functional disability (OR 1.82, 95% CI 1.28-2.60) but was not statistically significant after adjustment (aOR 1.23, 95% CI 0.81-1.86) and was not associated with increased disease activity. Non-white race/ethnicity was associated with higher disease activity (aOR 2.48, 95% CI: 1.41-4.36). Lower self-reported household income was associated with higher disease activity and persistent functional disability. Public insurance (aOR 1.56, 95% CI 1.06-2.29) and low family education (aOR 1.89, 95% CI 1.14-3.12) was associated with persistent functional disability.ConclusionHigh community poverty level was associated with persistent functional disability in unadjusted analysis but not with persistent moderate to high disease activity. Race/ethnicity and other SDH were associated with persistent disease activity and functional disability.

Selecting the Best Combined Biological Therapy for Refractory Inflammatory Bowel Disease Patients.

Current medical treatment for inflammatory bowel disease (IBD) does not achieve 100% response rates, and a subset of refractory and severely ill patients have persistent active disease after being treated with all possible drug alternatives. The combination of two biological therapies (CoT) seems a reasonable alternative, and has been increasingly tested in very difficult cases. The present review suggests that CoT seems to be safe and effective for refractory and severely ill IBD patients. Ustekinumab plus vedolizumab and vedolizumab plus anti-TNF were the most used CoTs for Crohn’s disease. For ulcerative colitis, the most used CoTs were vedolizumab plus anti-TNF and vedolizumab plus tofacitinib. The aforesaid CoTs have shown good efficacy and few adverse events have been reported.

Cluster analysis identifies unmet healthcare needs among patients with rheumatoid arthritis

Objective To identify the patterns of healthcare resource utilization and unmet needs of persistent disease activity, pain, and physical disability in rheumatoid arthritis (RA) by cluster analysis. Method Patients attending the Jyväskylä Central Hospital rheumatology unit, Finland, were, from 2007, prospectively enrolled in a clinical database. We identified all RA patients in 2010–2014 and combined their individual-level data with well-recorded administrative data on all public healthcare contacts in fiscal year 2014. We ran agglomerative hierarchical clustering (Ward’s method), with 28-joint Disease Activity Score with three variables, Health Assessment Questionnaire index, pain (visual analogue scale 0–100), and total annual health service-related direct costs (€) as clustering variables. Results Complete-case analysis of 939 patients derived four clusters. Cluster C1 (remission and low costs, 550 patients) comprised relatively young patients with low costs, low disease activity, and minimal disability. C2 (chronic pain, disability, and fatigue, 269 patients) included those with the highest pain and fatigue levels, and disability was fairly common. C3 (inflammation, 97 patients) had rather high mean costs and the highest average disease activity, but lower average levels of pain and less disability than C2, highlighting the impact of effective treatment. C4 (comorbidities and high costs, 23 patients) was characterized by exceptionally high costs incurred by comorbidities. Conclusions The majority of RA patients had favourable outcomes and low costs. However, a large group of patients was distinguished by chronic pain, disability, and fatigue not unambiguously linked to disease activity. The highest healthcare costs were linked to high disease activity or comorbidities.

What Does Disease Progression Look Like in Ulcerative Colitis, and How Might It Be Prevented?

Ulcerative colitis (UC) has been characterized by inflammation limited to the mucosa. Although sustained and durable remission has been associated with mucosal healing, the recurrent phenomenon of persistent clinical disease activity despite mucosal healing has been observed in clinical practice and across pivotal trials. Over time, UC appears to confer an increased risk of progression, defined as changes of disease phenotype; adverse transmural effects on the bowel wall; increased risk of neoplasia development; worsening colorectal function; and increased risk of colectomy, hospitalizations, and other extraintestinal comorbidities. Although the treatment paradigm for Crohn's disease has shifted toward early aggressive intervention to prevent disease progression and irreversible bowel damage, such urgency in efforts to halt disease progression in UC have been largely overlooked. This review summarizes the multiple facets of UC contributing to a modified perception of the disease as a progressive one. We propose further study of the natural history and priorities for further treatment goals that include these considerations.

DOP88 Long-term real-world data of ustekinumab in Crohn’s Disease – the Stockholm ustekinumab study – STOCUSTE

Abstract Background Ustekinumab (UST), an anti-interleukin-12/23 antibody, has successfully been introduced in the treatment of IBD, mainly in patients failing anti-TNF-agents. The STOCUSTE study includes IBD patients treated with UST at four teaching hospitals in Stockholm to provide long-term follow-up data. Here, we report the outcome in Crohn’s disease over the first 12 months. Methods This retrospective study includes patients diagnosed with Crohn’s disease and treated with UST who were followed until withdrawal of treatment for any reason, or until end of study, July 31, 2021. Disease activity (Harvey-Bradshaw Index (HBI); Physician Global Assessment (PGA), laboratory parameters and drug persistence were assessed. The primary outcome was remission (HBI ≤4; PGA = 0) and response (decrease HBI ≥3; PGA ≥1 from baseline) at 3 and 12 months, respectively. Results 120 patients, 61 women (51%), with a median age of 27 (IQR 27) at start of UST were included. All patients had luminal disease and 19 (16%) also fistulizing disease. 109 (91%) had failed ≥1 and 59 (49%) ≥2 anti-TNF drugs. In addition, 50 patients (42%) failed vedolizumab. At inclusion, 106 (88%) had active disease; 40 (33%) were on corticosteroid treatment and 22 (18%) on thiopurines. The persistence on UST was high, 93% at 3 months and 56% at 12 months. Of patients on UST at 3 months, 38% were in remission, and, at 12 months, 53%. An additional 26% were in response at 12 months. Of the 40 patients initially on corticosteroids, 17 (43%) and 28 (70%) had stopped steroids at 3 and 12 months, respectively. The median faecal calprotectin level declined from 272 (90–1763) at baseline to 75 (49–99) µg/g at 3 months (p&amp;lt;0.01). There was a slight decrease in CRP over 12 months, from 3 (2–12) to 1 (1–2) mg/l, together with increases in haemoglobin and serum albumin (n.s). Withdrawal from treatment during the first 12 months was 44% (53/120), mainly due to persisting disease activity. Four patients were withdrawn due to adverse events, three needed bowel surgery, two had malignancy and one patient suffered from systemic infection. Conclusion In this group of difficult-to-treat patients with Crohn’s disease, UST was shown to be effective in the majority, with high drug persistence at 12 months in combination with a favorable safety profile.

Sarcoidosis - a multisystem disease.

Sarcoidosis is a systemic inflammatory disease, characterised by granuloma formation upon an unknown trigger in genetically predisposed individuals. The inflammation is characterised by an activation of both the innate immune system, with macrophages differentiating into epitheloid cells and dendritic cells, and the adaptive immune system, particularly T helper (Th) 1 and Th17 cells. Since all organs can be affected to varying extents, clinical presentation is often diverse. Most commonly, the lungs, lymph nodes, skin and eyes are involved, whereas cardiac, renal and neurological manifestations are less common but associated with higher morbidity. Depending on the clinical symptoms, a detailed evaluation including thorough clinical examination, imaging and laboratory tests should explore all possible organ involvements. In some patients, fatigue manifests as a para-sarcoidosis symptom impacting quality of life, even if sarcoidosis is in remission. Some acute syndromic presentations, such as Löfgren's syndrome, have a good prognosis and are commonly self-limiting. If possible, a topical treatment, for example for cutaneous sarcoidosis or bronchial involvement, should be applied. Treatment of severe cases with persisting disease activity necessitates long-term immunosuppressive drugs, with glucocorticoids as the first-line option. Steroid-sparing and second-line drugs include methotrexate, azathioprine, mycophenolate mofetil and immunomodulators such hydroxychloroquine, with the latter being first-line therapy in cutaneous sarcoidosis. Tumour necrosis factor-alpha inhibitors (particularly adalimumab and infliximab) are used as third-line agents but are administered earlier in cases of persistent disease activity, severe organ-involvement or intolerance to conventional drugs. Treatment decisions should be based on a multidisciplinary approach, depending on organ involvement and treatment tolerability. Para-sarcoidosis manifestations, particularly fatigue, should also be carefully addressed, where the patient could also be enrolled in multidimensional rehabilitation programmes. With various organ involvement and different phenotypes, larger studies including real-world data from registries are necessary to evaluate different sarcoidosis endotypes and preferential treatment pathways.

Sarcoidosis - a multisystem disease.

Sarcoidosis is a systemic inflammatory disease, characterised by granuloma formation upon an unknown trigger in genetically predisposed individuals. The inflammation is characterised by an activation of both the innate immune system, with macrophages differentiating into epitheloid cells and dendritic cells, and the adaptive immune system, particularly T helper (Th) 1 and Th17 cells. Since all organs can be affected to varying extents, clinical presentation is often diverse. Most commonly, the lungs, lymph nodes, skin and eyes are involved, whereas cardiac, renal and neurological manifestations are less common but associated with higher morbidity. Depending on the clinical symptoms, a detailed evaluation including thorough clinical examination, imaging and laboratory tests should explore all possible organ involvements. In some patients, fatigue manifests as a para-sarcoidosis symptom impacting quality of life, even if sarcoidosis is in remission. Some acute syndromic presentations, such as Löfgren's syndrome, have a good prognosis and are commonly self-limiting. If possible, a topical treatment, for example for cutaneous sarcoidosis or bronchial involvement, should be applied. Treatment of severe cases with persisting disease activity necessitates long-term immunosuppressive drugs, with glucocorticoids as the first-line option. Steroid-sparing and second-line drugs include methotrexate, azathioprine, mycophenolate mofetil and immunomodulators such hydroxychloroquine, with the latter being first-line therapy in cutaneous sarcoidosis. Tumour necrosis factor-alpha inhibitors (particularly adalimumab and infliximab) are used as third-line agents but are administered earlier in cases of persistent disease activity, severe organ-involvement or intolerance to conventional drugs. Treatment decisions should be based on a multidisciplinary approach, depending on organ involvement and treatment tolerability. Para-sarcoidosis manifestations, particularly fatigue, should also be carefully addressed, where the patient could also be enrolled in multidimensional rehabilitation programmes. With various organ involvement and different phenotypes, larger studies including real-world data from registries are necessary to evaluate different sarcoidosis endotypes and preferential treatment pathways.

Putative Association between Low Baseline Gene Expression in the Peripheral Blood and Clinical Remission in Rheumatoid Arthritis Patients Treated with Tofacitinib.

We investigated the importance of the baseline expression of genes involved in energy generation, as prognostic biomarkers of the treatment response to tofacitinib in patients with rheumatoid arthritis (RA). Peripheral blood samples were obtained from 28 patients with RA who received 3 months of tofacitinib therapy from 26 healthy controls. Clinical response was evaluated based on the disease activity score, the erythrocyte sedimentation rate (DAS28-ESR), and the serum levels of ACPA, RF, CRP, and ESR. Clinical remission was assessed based on DAS28 score <2.6. Protein concentrations were measured using ELISA. Total RNA isolated from whole blood was used for gene expression analysis using quantitative RT-PCR. All patients were diagnosed with Steinbrocker’s radiographic stage II-III at baseline, and most showed erosive arthritis with ACPA and RF positivity. Tofacitinib treatment significantly decreased the disease activity. Upon study completion, seven patients showed remission. Before and after TOFA therapy, a significantly higher expression of succinate dehydrogenase and pyruvate kinase genes was observed in all the examined patients compared to healthy subjects. However, the pre-therapy expression of these genes and corresponding proteins was significantly (p ≤ 0.05) lower in patients who showed remission than in other patients with RA. Moreover, we observed that, during follow-up, patients who developed remission showed an increasing trend in the expression of the examined genes, whereas the others showed some decreases in gene expression, although this was not statistically significant. We concluded that, compared with RA patients maintaining persistent moderate or high disease activity, those with clinical remission following tofacitinib treatment showed a significantly lower baseline expression of genes involved in energy generation.

Системная красная волчанка: эпидемиология, отдаленные исходы и бремя болезни

The estimates of incidence and prevalence of systemic lupus erythematosus (SLE) in Europe are 1.5-4.9 per 100 000 persons-years and 30-70 per 100 000 people, respectively. Over the last 50 years, survival in SLE patients has improved significantly. Moreover, immunosuppressive treatment resulted in a decreased risk of death from active disease, whereas infections and cardiovascular disease have become the main causes of death in SLE populations. Almost 70% of SLE patients have recurrent course of disease, although long-term remissions or persistent disease activity also occur in a proportion of patients. Annually, every third SLE patient develops moderately severe or severe flares. Recurrent flares, complications of immunosuppressive treatment and comorbidity are associated with accrual of organ damage that increases the risk of death. SLE patients have impaired health-related quality of life correlating with both disease activity and organ damage. Being on remission of SLE or on low disease activity is associated with better outcomes, including lower mortality and risk of damage or flares, improved quality of life, lower hospitalisation rates and costs. Glucocorticoids remain the mainstay of SLE treatment, although their use should be limited, e.g. by proper administration of immunosuppressive or antiinflammatory agents that have steroid-sparing activity. Treatment and prevention of infections and cardiovascular outcomes are also essential for further improvement of survival of SLE patients.

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.