Previous analyses suggested that the HLA-DRB1 shared epitope (SE), and the IL4R V50I and the FcγRIIb I232T single nucleotide polymorphisms (SNPs) affected response to adalimumab (ADA) plus methotrexate (MTX)1. Their effect on long-term responses is unclear.
Objectives
To examine 78-wk clinical responses according to 3 candidate loci: HLA-DRB1 SE, and IL4R I50V and FcγRIIb I232T SNPs.
Methods
MTX-naïve patients (pts) ≥18 yr with RA <1 yr, active disease [DAS28 (CRP)>3.2, ESR≥28 mm/hr or CRP≥1.5 mg/dL], and >1 erosion, RF+, or anti-CCP+ were randomized to ADA+MTX or placebo (PBO)+MTX for 26 wks (Period 1, P1). Pts who achieved a stable LDA target (DAS28<3.2 at wks 22 & 26) with ADA+MTX were re-randomized to continue ADA+MTX or have ADA blindly withdrawn for 52 wks (P2). Pts who achieved the target with PBO+MTX continued blinded therapy. Pts who did not achieve the target were offered open-label (OL) ADA+MTX.
Results
Baseline demographics were similar across alleles. The table shows the percentage of pts achieving DAS28<3.2 at wk 78. There were no consistent patterns for the IL4R alleles in any group. While limited by small sample sizes, pts with FcγRIIb-CC appeared to have higher responses at wk 78 among groups initially exposed to ADA+MTX during P1. The positive influence of SE was apparent at wk 78 in groups originally exposed to ADA+MTX, particularly in pts who did not achieve the stable LDA target at wks 22 & 26 but continued ADA+MTX. However, this pattern was not observed in pts who failed to achieve the target with MTX and were subsequently treated with ADA+MTX. The interaction between SE and IL4R observed during P1 was not apparent in long-term responses to ADA+MTX.
Conclusions
Regardless of genetic background, wk 78 responses were generally higher for pts who achieved the stable LDA target at wks 22 & 26. The positive effects of HLA-DRB1 SE and FcγRIIb-CC in response to ADA+MTX previously noted at wk 26 were less apparent at wk 78, but noticeable in pts who failed to achieve the target. Further, while SE predicted clinical response to ADA+MTX, particularly when combined with IL4R alleles, it had no influence on the ability to withdraw ADA in pts who achieved LDA. These findings may indicate that genetic factors have a stronger influence on initial treatment response than on sustained disease control.
References
Skapenko et al. EULAR 2011 #THU0309.
Disclosure of Interest
A. Skapenko: None Declared, J. Smolen Grant/Research support from: Abbott, Amgen, Astra-Zeneca, BMS, Celgene Centocor-Janssen, Glaxo, Lilly, Pfizer (Wyeth), MSD (Schering-Plough), Novo-Nordisk, Roche, Sandoz, UCB, Consultant for: Abbott, Amgen, Astra-Zeneca, BMS, Celgene Centocor-Janssen, Glaxo, Lilly, Pfizer (Wyeth), MSD (Schering-Plough), Novo-Nordisk, Roche, Sandoz, UCB, A. Kavanaugh Grant/Research support from: Abbott, Amgen, Astra-Zeneca, BMS, Celgene, Centocor-Janssen, Pfizer, Roche, and UCB, Consultant for: Abbott, Amgen, Astra-Zeneca, BMS, Celgene, Centocor-Janssen, Pfizer, Roche, and UCB, S. Santra Shareholder of: Abbott, Employee of: Abbott, H. Kupper Shareholder of: Abbott, Employee of: Abbott, H. Schulze-Koops Consultant for: Abbott
Tenosynovitis is a prominent feature of rheumatoid arthritis (RA) (1). Chronic tenosynovitis can lead to tendon rupture, resulting in substantial functional impairment. Ultrasound has proven to be a valid instrument for the detection and evaluation not only of synovitis but also tenosynovitis. Just recently, consensus criteria for the assessment of tenosynovitis were developed by the OMERACT task force (2).
Objectives
To describe the prevalence of tenosynovitis in an untreated early RA cohort, to evaluate the contribution of tenosynovitis to small joint tenderness and swelling, and to assess the response of tenosynovitis to therapy.
Methods
Patients with newly diagnosed and therapy-naive RA were included in the study and assessed by clinical examination and ultrasound. Ultrasound of the palmar metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints and the flexor tendons was performed with grey scale (GSUS) and power Doppler (PDUS) ultrasound. Synovitic findings in GSUS and PDUS were graded semiquantitatively from 0 to 3, tenosynovitic findings were graded binary for GSUS and semiquantitatively for PDUS as specified before (3, 4). After the initial assessment, patients were treated according to national guidelines and were seen on a regular outpatient basis. Clinical and sonographic reevaluation was performed at month 6. The prevalences of synovitis and tenosynovitis at baseline and follow up were assessed and compared. Subgroup analysis for tenosynovitis in clinically inapparent (i.e. subclinical) and clinically affected joints was perfomed. P-values less than 0.05 were considered significant.
Results
Data of 60 patients with early untreated RA was available for analysis. At baseline, overall prevalence of flexor tendon tenosynovitis was 22.5% with PDUS grades 0, 1, 2, and 3 detected in 42.0%, 15.8%, 39.3%, and 2.8%, respectively. MCP and PIP joints were affected by synovitis in 42.2% and 44.1%. At baseline, overall prevalence of subclinical flexor tendon tenosynovitis was 14.8%, while subclinical synovitis was present in 33.0% and 28.3% of the MCP and PIP joints, respectively. In clinically affected fingers, tenosynovitis was detected in 37.6%. Of these, 29.1% occurred in association with small joint synovitis while in 8.5% no articular findings were detected. Small joint synovitis alone was detected in 36.5%. At follow up after 6 months, overall prevalence of flexor tendon tenosynovitis was 5.0%, while synovitis of the MCP and PIP joints was present in 17.1% and 16.3%, respectively (p<0.001 versus baseline for tenosynovitis, MCP and PIP).
Conclusions
Ultrasound data from this prospective early RA cohort show a high prevalence of flexor tendon tenosynovitis and an association with small joint synovitis. Both tenosynovitis and synovitis contribute to clinical tenderness and swelling, but can also occur subclinically. The role of flexor tendon tenosynovitis as a sole contributor to clinical symptoms in RA seems to be of minor importance. Upon treatment, flexor tendon tenosynovitis has a significantly better response than small joint synovitis.
References
Wakefield J et al., Arthritis Rheum 2007;57:1158 Naredo E et al., Ann Rheum Dis 2013;72:1328 Backhaus M et al, Arthritis Rheum 2009;61:1194 Alcalde M et al., Rheumatology 2012;51:1246
Im September 2019 wurde vom Ministerium fur Arbeit, Gesundheit und Soziales (MAGS) in NRW ein Gutachten zur Krankenhausplanung veroffentlicht. Hierin wurde eine grundlegende Reform der Krankenhausplanung empfohlen, indem zukunftig eine Bedarfsplanung auf der Grundlage einer detaillierten Ausweisung von Leistungsbereichen und Leistungsgruppen erfolgen soll. Nach Aufforderung durch das MAGS NRW hat auch die Deutsche Gesellschaft fur Rheumatologie (DGRh) mit Unterstutzung des Verbandes Rheumatologischer Akutkliniken (VRA) hierzu Stellung genommen.
Zusatzmaterial online
Die Online-Version dieses Beitrags (10.1007/s00393-020-00939-4) enthalt eine Tabelle zur Zuordnung von Qualitatsvorgaben fur Leistungsgruppen. Beitrag und Zusatzmaterial stehen Ihnen auf www.springermedizin.de zur Verfugung. Bitte geben Sie dort den Beitragstitel in die Suche ein, das Zusatzmaterial finden Sie beim Beitrag unter „Erganzende Inhalte“.
The first EULAR provisional recommendations on the management of rheumatic and musculoskeletal diseases (RMDs) in the context of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), largely based on expert opinion, were published in June 2020. Since then, an unprecedented number of clinical studies have accrued in the literature. Several SARS-CoV-2 vaccines have been approved for population-wide vaccination programmes in EULAR-affiliated countries. Studies regarding vaccination of patients with (inflammatory) RMDs have released their first results or are underway. EULAR found it opportune to carefully review to what extent the initially consensus expert recommendations stood the test of time, by challenging them with the recently accumulated body of scientific evidence, and by incorporating evidence-based advice on SARS-CoV-2 vaccination. EULAR started a formal (first) update in January 2021, performed a systematic literature review according to EULAR’s standard operating procedures and completed a set of updated overarching principles and recommendations in July 2021. Two points to consider were added in November 2021, because of recent developments pertaining to additional vaccination doses.
BackgroundThe role of Th17 cells in the pathogenesis of human autoimmune diseases is elusive.To gain insights into the role of Th17 cells in human autoimmune diseases, the authors analysed Th17 cells in patients with prototypic autoimmune diseases such as rheumatoid arthritis (RA) and psoriatic arthritis (PsA).Methods and Results Th17 cells were analysed in well-defi ned homogeneous cohorts of patients: treatment-naive patients with active early RA (n=6; disease duration 2.8 months; disease activity score 28 (DAS28) 5.0) and PsA (n=9; disease duration 2.3 months), and patients with established RA responding or not responding to therapy with methotrexate/adalimumab (n=1; mean disease duration 68 months).Healthy individuals and patients with osteoarthritis were used as control cohorts.Th17 cell frequencies and IL17 production strongly correlated with systemic disease activity at both the onset and the progression of the diseases.They were reduced to control levels in response to clinically effective treatment.Th17 cells were enriched in the joints, and increased frequencies of synovial Th17 cells expressed CCR4 and CCR6, indicative of selective migration of Th17 cells to the joints.The intrinsically elevated expression of the master transcription factor for Th17 cells, RORC, accompanied by biased Th17 cell development and a resistance of Th17 cells from the patients to natural on July 29, 2023 by guest.
Familial mediterranean fever (FMF) is the most prevalent hereditary autoinflammatory disorder. While disease features such as fever, polyserositis and systemic amyloidosis are well recognized, little is known about the involvement of the autonomous nervous system. However, autonomic dysfunction has been identified as a major problem in autoimmune diseases such as systemic lupus erythematosus and diabetes mellitus (1). Resulting morbidities include orthostatic and gastrointestinal dysregulation and reduced heart rate variability.
Objectives
To prospectively investigate whether signs and symptoms of autonomic dysfunction are more prevalent in FMF patients than in age and gender matched healthy controls.
Methods
Patients fulfilling the classification criteria for FMF were included in the study. Data on genotype, disease activity, disease manifestations, current treatment and presence/absence of amyloidosis was gathered. Patients and healthy controls were evaluated using the COMPASS-31 questionnaire, a well-validated and feasible self-assessment instrument for the evaluation of autonomic functions and symptoms (2). Additional tests included assessment of blood pressure responses to sympathic and parasympathic stimuli, heart rate variability analysis and skin conductance measurement.
Results
Sofar, 18 FMF patients and 15 healthy controls were enrolled into this ongoing study. Mean age and gender distribution did not differ significantly in both groups. Compared to healthy controls, FMF patients had a significantly higher mean COMPASS-31 score (20.7±6.8 vs. 7.1±5.3, p<0.05). This difference remained significant after the GI domain of the COMPASS-31 questionnaire was excluded from analysis (15.2±5.5 vs. 6.2±4.3, p<0.05). Concerning the COMPASS-31 subdomains, mean scores in the vasomotor, secretomotor and GI domain were significantly higher in the FMF group than in the control group (p<0.05 each), while there were no differences between patients and controls in the orthostatic, bladder and pupillomotor domain. Preliminary results of the biometric tests confirm the COMPASS-31 findings.
Conclusions
The presented data implies autonomic dysfunction in patients with FMF. Thorough assessment of FMF patients for the presence of ANS pathology seems to be warranted. Research involving biometric tests involving the assessment of blood pressure responses to sympathic and parasympathic stimuli, heart rate variability analysis and skin conductance measurement are now in progress to further clarify these results.
References
Stojanovich L et al.: Autonomic dysfunction in autoimmune rheumatic disease. Autoimmun Rev 2009; 8: 569-72. Sletten DM et al.: COMPASS-31: a refined and abbreviated Composite Autonomic Symptom Score. Mayo Clin Proc 2012;87:1196-201.
Key Clinical Message In women of childbearing age, severe proteinuria in systemic lupus erythematosus raises concern for renal involvement and pregnancy complications. While persisting renal loss of protein is known to culminate in extensive interventions, intermittent proteinuria in inactive disease requires an adjusted approach. Contextual awareness of this urinary finding is thus essential.
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