Background: Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are inflammatory diseases that often affect the wrist and, when affected, can lead to impaired wrist function and progressive... Show moreBackground: Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are inflammatory diseases that often affect the wrist and, when affected, can lead to impaired wrist function and progressive joint destruction if inadequately treated. Standard care consists primarily of disease-modifying anti-rheumatic drugs (DMARDs), often supported by systemic corticosteroids or intra-articular corticosteroid injections (IACSI). IACSI, despite their use worldwide, show poor response in a substantial group of patients. Arthroscopic synovectomy of the wrist is the surgical removal of synovitis with the goal to relieve pain and improve wrist function. The primary objective of this study is to evaluate wrist function following arthroscopic synovectomy compared to IACSI in therapy-resistant patients with rheumatoid or psoriatic arthritis. Secondary objectives include radiologic progress, disease activity, health-related quality of life, work participation and cost-effectiveness during a 1-year follow-up. Methods: This protocol describes a prospective, randomized controlled trial. RA and PsA patients are eligible with prominent wrist synovitis objectified by a rheumatologist, not responding to at least 3 months of conventional DMARDs and naive to biological DMARDs. For 90% power, an expected loss to follow-up of 5%, an expected difference in mean Patient-Rated Wrist Evaluation score (PRWE, range 0-100) of 11 and alpha = 0.05, a total sample size of 80 patients will be sufficient to detect an effect size. Patients are randomized in a 1:1 ratio for arthroscopic synovectomy with deposition of corticosteroids or for IACSI. Removed synovial tissue will be stored for an ancillary study on disease profiling. The primary outcome is wrist function, measured with the PRWE score after 3 months. Secondary outcomes include wrist mobility and grip strength, pain scores, DAS28, EQ-5D-5L, disease progression on ultrasound and radiographs, complications and secondary treatment. Additionally, a cost-effectiveness analysis will be performed, based on healthcare costs (iMCQ questionnaire) and productivity loss (iPCQ questionnaire). Follow-up will be scheduled at 3, 6 and 12 months. Patient burden is minimized by combining study visits with regular follow-ups. Discussion: Persistent wrist arthritis continues to be a problem for patients with rheumatic joint disease leading to disability. This is the first randomized controlled trial to evaluate the effect, safety and feasibility of arthroscopic synovectomy of the wrist in these patients compared to IACSI.Trial registration: Dutch trial registry (CCMO), NL74744.100.20. Registered on 30 November 2020.ClinicalTrials.gov NCT04755127. Registered after the start of inclusion on 15 February 2021. Show less
BackgroundRheumatoid arthritis (RA) and psoriatic arthritis (PsA) are inflammatory diseases that often affect the wrist and, when affected, can lead to impaired wrist function and progressive joint... Show moreBackgroundRheumatoid arthritis (RA) and psoriatic arthritis (PsA) are inflammatory diseases that often affect the wrist and, when affected, can lead to impaired wrist function and progressive joint destruction if inadequately treated. Standard care consists primarily of disease-modifying anti-rheumatic drugs (DMARDs), often supported by systemic corticosteroids or intra-articular corticosteroid injections (IACSI). IACSI, despite their use worldwide, show poor response in a substantial group of patients. Arthroscopic synovectomy of the wrist is the surgical removal of synovitis with the goal to relieve pain and improve wrist function. The primary objective of this study is to evaluate wrist function following arthroscopic synovectomy compared to IACSI in therapy-resistant patients with rheumatoid or psoriatic arthritis. Secondary objectives include radiologic progress, disease activity, health-related quality of life, work participation and cost-effectiveness during a 1-year follow-up.MethodsThis protocol describes a prospective, randomized controlled trial. RA and PsA patients are eligible with prominent wrist synovitis objectified by a rheumatologist, not responding to at least 3 months of conventional DMARDs and naïve to biological DMARDs. For 90% power, an expected loss to follow-up of 5%, an expected difference in mean Patient-Rated Wrist Evaluation score (PRWE, range 0–100) of 11 and α = 0.05, a total sample size of 80 patients will be sufficient to detect an effect size. Patients are randomized in a 1:1 ratio for arthroscopic synovectomy with deposition of corticosteroids or for IACSI. Removed synovial tissue will be stored for an ancillary study on disease profiling. The primary outcome is wrist function, measured with the PRWE score after 3 months. Secondary outcomes include wrist mobility and grip strength, pain scores, DAS28, EQ-5D-5L, disease progression on ultrasound and radiographs, complications and secondary treatment. Additionally, a cost-effectiveness analysis will be performed, based on healthcare costs (iMCQ questionnaire) and productivity loss (iPCQ questionnaire). Follow-up will be scheduled at 3, 6 and 12 months. Patient burden is minimized by combining study visits with regular follow-ups.DiscussionPersistent wrist arthritis continues to be a problem for patients with rheumatic joint disease leading to disability. This is the first randomized controlled trial to evaluate the effect, safety and feasibility of arthroscopic synovectomy of the wrist in these patients compared to IACSI. Show less
In this thesis two main aims were addressed. It has long been established that early treatment of rheumatoid arthritis (RA) improves disease outcomes. In Part I of this thesis we therefore further... Show moreIn this thesis two main aims were addressed. It has long been established that early treatment of rheumatoid arthritis (RA) improves disease outcomes. In Part I of this thesis we therefore further investigated the early detection of at-risk individuals by studying a large cohort of patients with clinically suspect arthralgia (CSA). We explored the value of two easy clinical tests, their potential to detect underlying inflammatory processes and to predict disease progression. In addition we investigated the presence of subclinical synovitis on imaging as starting point for treatment with disease modifying anti-rheumatic drugs (DMARDs) and the value of magnetic resonance imaging (MRI) detected erosions as new predictor for RA-development. In Part II of this thesis we aimed to determine which disease processes are involved in the different phases of RA-development. Knowledge on disease pathogenesis and timing of influencing factors can help to better target treatment during RA-development. We therefore evaluated whether autoantibody-response maturation occurred during the phase of CSA, and investigated the timing of genetic risk factor human leukocyte antigen-shared epitope (HLA-SE) and environmental risk factor smoking during the development of autoantibody-positive disease. Show less
Rheumatoid arthritis (RA) is a disease of the synovium that involves the small joints of hands and feet. The focus in RA-research, however, has primarily been on involvement of the hands. In this... Show moreRheumatoid arthritis (RA) is a disease of the synovium that involves the small joints of hands and feet. The focus in RA-research, however, has primarily been on involvement of the hands. In this thesis we studied involvement of the forefoot. Throughout this thesis we found that synovitis in the rheumatoid foot affects more than just the joints. In an anatomic study we revealed that the tendon-sheaths in the forefoot also possess a synovial layer. Inflammation of this, detected by MRI that is referred to as tenosynovitis, was an important aspect of RA involvement in the forefoot. In addition, intermetatarsal bursae also detected by MRI are also often inflamed due to disease-involvement. These extra-articular involvements of the synovium that are found in RA importantly contribute to joint swelling and walking disability, and are therefore clinically relevant. Therefore we believe that it is essential for the clinician to pay attention to the forefeet of patients with RA to have a complete idea of disease activity Show less
Romao, V.C.; Humby, F.; Kelly, S.; Cicco, M. di; Mahto, A.; Lazarou, I.; ... ; Pitzalis, C. 2020
Background: Clinical outcomes in elderly-onset rheumatoid arthritis (EORA), starting after the age of 60, are conflicting. Thus, we aimed to investigate in a unique biopsy-driven, treatment-naive... Show moreBackground: Clinical outcomes in elderly-onset rheumatoid arthritis (EORA), starting after the age of 60, are conflicting. Thus, we aimed to investigate in a unique biopsy-driven, treatment-naive early arthritis cohort, the relationship between synovial pathobiology of elderly- (EORA) and younger-onset rheumatoid arthritis (YORA) patients through clinical, imaging and treatment response outcome-measures.Methods: Patients (n = 140) with early RA (<12months) starting before (YORA, n = 99) or after (EORA, n = 41) age 60 had an ultrasound-guided synovial biopsy prior to conventional immunosuppressive therapy and after 6 months. Clinical, ultrasound and radiographic data were collected prospectively and compared between groups and against immunohistological features. Using multivariate logistic regression, we determined predictors of clinical response (disease activity score-28-erythrocyte sedimentation rate [DAS28-ESR]<3.2) at 6months and radiographic progression (>= 1-unit-increase in Sharp van der Heijde [SvdH] score) at 12months.Results: EORA patients were more frequently male and presented most commonly with an abrupt, polymyalgia rheumatica-like onset and extra-articular features. Both before and after treatment, DAS28-ESR was similar but ultrasound synovial-thickening (p<0.05) and power-Doppler (p<0.01) synovitis and SvdH (p<0.001) scores were higher in EORA patients. EORA was independently associated with poor treatment response at 6 months (OR=0.28, p = 0.047) and radiographic progression at 12 months (OR=4.08, p = 0.029). Synovial pathotype, synovitis scores and cellular infiltration were similar before treatment, but a pauci-immune-fibroid pathotype tended to be more common in YORA at 6 months (p = 0.093). Moreover, YORA patients had a marked improvement of all synovitis parameters (p<0.001), whereas EORA presented only mild decreases in synovitis (p<0.05), sublining macrophage (p<0.05) and T cell scores (p<0.05), with no significant changes in lining macrophages, B cells or plasma cells.Conclusion: Early EORA presents differently and has a worse overall prognosis than YORA, with poorer clinical, histological, ultrasonographic and radiographic outcomes. (C) 2020 Elsevier Inc. All rights reserved. Show less
Najm, A.; Alunno, A.; Sivera, F.; Ramiro, S.; Haines, C.; Working Grp Training Rheumatology 2020
Objectives To gain insight into current methods and practices for the assessment of competences during rheumatology training, and to explore the underlying priorities and rationales for competence... Show moreObjectives To gain insight into current methods and practices for the assessment of competences during rheumatology training, and to explore the underlying priorities and rationales for competence assessment.Methods We used a qualitative approach through online focus groups (FGs) of rheumatology trainers and trainees, separately. The study included five countries-Denmark, the Netherlands, Slovenia, Spain and the United Kingdom. A summary of current practices of assessment of competences was developed, modified and validated by the FGs based on an independent response to a questionnaire. A prioritising method (9 Diamond technique) was then used to identify and justify key assessment priorities.Results Overall, 26 participants (12 trainers, 14 trainees) participated in nine online FGs (2 per country, Slovenia 1 joint), totalling 12 hours of online discussion. Strong nationally (the Netherlands, UK) or institutionally (Spain, Slovenia, Denmark) standardised approaches were described. Most groups identified providing frequent formative feedback to trainees for developmental purposes as the highest priority. Most discussions identified a need for improvement, particularly in developing streamlined approaches to portfolios that remain close to clinical practice, protecting time for quality observation and feedback, and adopting systematic approaches to incorporating teamwork and professionalism into assessment systems.Conclusion This paper presents a clearer picture of the current practice on the assessment of competences in rheumatology in five European countries and the underlying rationale of trainers' and trainees' priorities. This work will inform EULAR Points-to-Consider for the assessment of competences in rheumatology training across Europe. Show less
Rheumatoid arthritis is a heterogeneous disease, which can be, based on data combining genetic risk factors and autoantibodies, sub-classified into ACPA-positive and -negative RA. Presence of ACPA... Show moreRheumatoid arthritis is a heterogeneous disease, which can be, based on data combining genetic risk factors and autoantibodies, sub-classified into ACPA-positive and -negative RA. Presence of ACPA and RF as well as rising CRP-levels in some patients years before onset of clinical symptoms indicate that relevant immune responses for RA development are initiated very early. ACPA are highly specific for RA, whereas RF can also be found among healthy (elderly) individuals and patients with other autoimmune diseases or infection. The most important genetic risk factor for RA development, the shared epitope alleles, resides in the MHC class II region. Shared epitope alleles, however, only predispose to the development of ACPA-positive RA. Smoking is thus far the most important environmental risk factor associated with the development of RA. Studies on synovitis have shown the importance not only of adaptive but also of innate immune responses. In summary of the various results from immunological changes in blood and synovial tissue, the extension of the immune response from a diffuse myeloid to a lympho-myeloid inflammation appears to be associated with a more successful therapeutic response to biologics. With respect to advances in synovitis research, new targets for treatment against pathological subsets of immune cells or fibroblasts are already on the horizon. However, alternative strategies involving the microbiome may play an important role as well and research in this field is growing rapidly. Show less
Ohrndorf, S.; Boer, A.C.; Boeters, D.M.; Brinck, R.M. ten; Burmester, G.R.; Kortekaas, M.C.; Helm-van Mil, A.H.M. van der 2019
This thesis discusses several aspects of therapeutic interventions for arthritis of the knee, especially arthroscopic lavage. Arthroscopic lavage is a technique in which the inflamed knee of the... Show moreThis thesis discusses several aspects of therapeutic interventions for arthritis of the knee, especially arthroscopic lavage. Arthroscopic lavage is a technique in which the inflamed knee of the patient is rinced with saline. After the procedure corticosteroids can be administered to suppress inflammation. Arthroscopic lavage was superior in suppressing recurrence of arthritis compared to standard joint injections with corticosteroids. The occurence of fibrosis in the inflamed joint was predictive of an inferior response. During arthroscopic lavage synovial tissue samples can be obtained. These biopsies were studied before and after treatment with anti-TNF in longstanding and early (therapy-naieve) Rheumatoid Arthritis (RA)patients. The clinical and synovial effect were comparable between both groups. In the latter part differences in synovial inflamation between RA patients with and without antibodies against cyclic citrullinated peptides (CCP) are discussed in relation to the occurence of joint damage. In anti-CCP positive patients we found more infiltrating lymphocytes leading to progression of joint damage. Also, temporal changes in synovial inflammation differed between anti-CCP positive and anti_CCP negative RA, underlining the fenotypical differences betwen both disease entities. Show less
