Who stop telemonitoring disease activity and who adhere: a prospective cohort study of patients with inflammatory arthritis.

BACKGROUND: The use of frequent electronic patient reported outcome measures (ePRO's) enables monitoring disease activity at a distance (telemonitoring) in patients with inflammatory arthritis. However, telemonitoring studies report declining long-term adherence to reporting ePRO's, which may oppose the benefits of telemonitoring. Therefore, the objective was to investigate what factors are associated with (non-)adherence to telemonitoring with a weekly ePRO in patients with inflammatory arthritis (IA). METHODS: We performed a prospective cohort study in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) at Reade Amsterdam, The Netherlands. Patients telemonitored their disease activity weekly for 6 months with a modified Multidimensional Health Assessment Questionnaire completed in a smartphone application. The primary outcome was time to dropout, defined as ≥ 4 weeks of consecutively nonresponse. Based on literature and through expert meetings, a predefined set of 13 baseline factors were selected to assess the association with time to dropout through a multivariable Cox-regression analysis. RESULTS: A total of 220 consecutive patients were included (mean age 54, SD 12; 55% females; 99 RA, 81 PsA, and 40 AS). A total of 141 patients (64%) dropped out, with a median time to dropout of 17 weeks (IQR 9-26). Women had a significant higher chance to dropout over 6 months compared to men (HR 1.58, 95% CI 1.06-2.36). CONCLUSION: In the set of investigated factors, women stopped reporting the weekly ePRO sooner than men. Future focus group discussions will be performed to investigate the reasons for dropout, and in specific why women dropped out sooner. Trial registration This trials was prospectively registered at www.trialregister.nl (NL8414).

The RAPID3 questionnaire as a screening tool to reduce the number of outpatient clinic visits: a retrospective cohort study.

BACKGROUND: Treat-to-target strategies require frequent on-site evaluations of disease activity in patients with rheumatoid arthritis (RA), burdening patients and caregivers. However, this frequency may not be required in patients in a stable low disease activity state. The Routine Assessment of Patient Index Data 3 (RAPID3) is a reliable tool to detect such states in groups but has not been tested to reduce the frequency of on-site evaluations in individual patient care. In Reade, an outpatient rheumatology clinic, patients can complete the questionnaire online prior to consultation, and the results are directly fed into the electronic patient record. Focusing on low disease activity, we retrospectively studied the test characteristics of RAPID3 and its agreement with the DAS28 in our database of routine patient care. OBJECTIVE: To assess the test characteristics and agreement between de DAS28 and the RAPID3 in patients with RA, with a focus on the low disease activity categories. METHODS: We performed a retrospective database study with available clinical data collected as part of usual care from the electronic medical record at Reade Amsterdam. The dataset comprised RAPID3 assessments followed by a DAS28 within 2 weeks, obtained between June 2014 and March 2021. We dichotomized the disease activity categories for both the RAPID3 and DAS28 into low (remission and low disease activity) and high (moderate and high disease activity). With cutoff values of 2.0 for RAPID3 and 3.2 for DAS28, we calculated test characteristics and agreement (Cohen's kappa). RESULTS: A total of 5009 combined RAPID3 and DAS28 measurements were done at Reade in 1681 unique RA patients. The mean age was 60 years, and 76% of patients were female with a median disease duration of 4 years. Agreement was considered fair (kappa = 0.26). In total, 1426 (28%) of the RAPID3 measurements were classified as low and could be potentially targeted to skip their consultations. The sensitivity to detect low disease activity was 0.39, specificity was 0.93, and the positive predictive value was 0.92. CONCLUSION: We showed that when the RAPID3 classifies a patient into low disease activity state, the accuracy is 92%. Of all consultations, 28% could possibly be postponed following the screening with RAPID3.

Spinning straw into gold: description of a disruptive rheumatology research platform inspired by the COVID-19 pandemic.

Clinical research projects often use traditional methods in which data collection and signing informed consent forms rely on patients' visits to the research institutes. However, during challenging times when the medical community is in dire need of information, such as the current COVID-19 pandemic, it becomes more urgent to use digital platforms that can rapidly collect data on large numbers of patients. In the current manuscript, we describe a novel digital rheumatology research platform, consisting of almost 5000 patients with autoimmune diseases and healthy controls, that was set up rapidly during the COVID-19 pandemic, but which is sustainable for the future. Using this platform, uniform patient data can be collected via questionnaires and stored in a single database readily available for analysis. In addition, the platform facilitates two-way communication between patients and researchers, so patients become true research partners. Furthermore, blood collection via a finger prick for routine and specific laboratory measurements has been implemented in this large cohort of patients, which may not only be applicable for research settings but also for clinical care. Finally, we discuss the challenges and potential future applications of our platform, including supplying tailored information to selected patient groups and facilitation of patient recruitment for clinical trials.

Different stages of rheumatoid arthritis: features of the synovium in the preclinical phase.

BACKGROUND: The aetiology of rheumatoid arthritis (RA), a prototype immune-mediated inflammatory disorder, is poorly understood. It is currently unknown whether the disease process starts in the synovium, the primary target of RA, or at other sites in the body. OBJECTIVE: To examine, in a prospective study, the presence of synovitis in people with an increased risk of developing RA. METHODS: Thirteen people without evidence of arthritis, who were positive for IgM rheumatoid factor and/or anticitrullinated protein antibodies, were included in the study. To evaluate synovial inflammatory changes, all participants underwent dynamic contrast-enhanced MRI and arthroscopic synovial biopsy sampling of a knee joint at inclusion. Results were compared with knee MRI data and synovial biopsy data of 6 and 10 healthy controls, respectively. RESULTS: MRI findings evaluated by measurement of maximal enhancement, rate of enhancement, synovial volume and enhancement shape curve distribution were similar between the autoantibody-positive subjects and the healthy controls. Consistent with these findings, all but one autoantibody-positive subject showed very low scores for phenotypic markers, adhesion molecules and vascularity, all in the same range as those in normal controls. The one person with higher scores had patellofemoral joint space narrowing. CONCLUSION: Subclinical inflammation of the synovium does not coincide with the appearance of serum autoantibodies during the pre-RA stage. Thus, systemic autoimmunity precedes the development of synovitis, suggesting that a 'second hit' is involved. This study supports the rationale for exploring preventive strategies aimed at interfering with the humoral immune response before synovial inflammation develops.

Effect of dexamethasone on autoantibody levels and arthritis development in patients with arthralgia: a randomised trial.

BACKGROUND: Rheumatoid arthritis is characterised by antibodies to citrullinated proteins (ACPA) and rheumatoid factor (RF) in the preclinical phase. OBJECTIVE: To determine whether an intervention aimed at decreasing autoantibody levels in people at risk may be effective in preventing progression to arthritis. METHODS: 83 patients with arthralgia positive for ACPA or IgM-RF were randomly allocated to intramuscular injections of 100 mg dexamethasone or placebo at baseline and 6 weeks. The primary end point was a 50% antibody reduction or normalisation at 6 months. RESULTS: The primary end point was reached in one patient in each group. Patients treated with dexamethasone had reductions of antibody levels after 1 month (ACPA 222% and IgM-RF 214%), which persisted at 6 months for ACPA. During a median follow-up of 26 months, arthritis development in both groups was similar (20% vs 21%). CONCLUSION: In autoantibody-positive patients with arthralgia, dexamethasone treatment decreases ACPA and IgM-RF levels, but does not prevent arthritis development. TRIAL REGISTRATION NUMBER: ISRCTN73232918.

Arthritis development in patients with arthralgia is strongly associated with anti-citrullinated protein antibody status: a prospective cohort study.

BACKGROUND: Anti-citrullinated protein antibodies (ACPA) are associated with increased risk for rheumatoid arthritis. OBJECTIVE: To investigate the effect of the presence and levels of ACPA on arthritis development in patients with arthralgia. METHODS: Patients with arthralgia positive for ACPA or IgM rheumatoid factor (IgM-RF) were tested for the shared epitope (SE) and were prospectively followed up for at least 12 months. Absence of clinical arthritis at inclusion and arthritis development during follow-up were independently confirmed by two investigators. Cox regression hazard analyses were used to calculate hazard ratios (HRs) for arthritis development. RESULTS: 147 patients with arthralgia were included (50 ACPA positive, 52 IgM-RF positive and 45 positive for both antibodies). After a median follow-up of 28 months (interquartile range (IQR) 19-39), 29 patients developed arthritis in a median of 4 (IQR 3-6) joints and 26 (90%) of these were ACPA positive. The presence of ACPA (HR = 6.0; 95% confidence interval (95% CI) 1.8 to 19.8; p = 0.004), but not of IgM-RF (HR = 1.4, 95% CI 0.6 to 3.1) nor the SE (HR = 1.5, 95% CI 0.7 to 3.0), was associated with arthritis development. Within the group of ACPA-positive patients, the risk for arthritis was enhanced by the presence of IgM-RF (HR = 3.0; 95% CI 1.4 to 6.9; p = 0.01) and high ACPA levels (HR = 1.7; 95% CI 1.1 to 2.5; p = 0.008), but not the SE (HR = 1.0; 95% CI 0.5 to 2.1; p = 1.0). CONCLUSION: In patients with arthralgia the presence of ACPA (but not of IgM-RF or SE) predicts arthritis development. The risk in ACPA-positive patients may be further increased by the concomitant presence of IgM-RF or high levels of ACPA.

Preferential decrease in IgG4 anti-citrullinated protein antibodies during treatment with tumour necrosis factor blocking agents in patients with rheumatoid arthritis.

OBJECTIVE: To investigate the dynamics of IgG1 and IgG4 anti-citrullinated protein antibody (ACPA) subclasses during anti-tumour necrosis factor (TNF) treatment in patients with rheumatoid arthritis (RA). METHODS: IgG, IgG1 and IgG4 ACPA levels were determined by ELISA on anti-citrullinated fibrinogen (ACF) and IgG1 : IgG4 ACPA ratios were calculated. A pilot study was performed in 28 ACF-positive patients treated with infliximab for one year. Confirmation of the results was obtained using a cohort of 180 consecutive patients treated with adalimumab for 28 weeks. RESULTS: The median reduction in ACF levels was 31% for total IgG, 29% for IgG1, 40% for IgG4 and 22% for the IgG4 : IgG1 ACF ratio in the infliximab cohort. In adalimumab-treated patients, ACF levels declined 14% for total IgG and IgG1, and 36% for IgG4 ACF; the IgG4 : IgG1 ratio was reduced by 24% (all percentage values p<0.05). The decrease in antibody levels was correlated with the clinical response; European League Against Rheumatism good responders had the greatest decline in antibody levels and this effect was most pronounced for IgG4 (48% reduction). The IgG4 : IgG1 ACF ratio preferentially decreased in patients with adequate therapeutic adalimumab levels. CONCLUSION: ACPA subclass distribution is modulated by effective anti-inflammatory treatment. The preferential decline of IgG4 ACPA, reflected by the decreased IgG4 : IgG1 ratio, suggests a beneficial effect of anti-TNF treatment on chronic antigenic stimulation by citrullinated proteins. This effect may be directly anti-TNF mediated or the result of effective dampening of the inflammation in the rheumatoid joint.

The role of the shared epitope in arthralgia with anti-cyclic citrullinated peptide antibodies (anti-CCP), and its effect on anti-CCP levels.

OBJECTIVES: Patients presenting with both arthralgia and antibodies to cyclic citrullinated peptide (anti-CCP) have an increased risk of developing rheumatoid arthritis (RA). To further characterise this patient group and shed more light on its relationship with clinically manifest early arthritis and established RA, an immunogenetic and serological analysis was performed. METHODS: In a group of 111 patients with anti-CCP-positive arthralgia, anti-CCP levels and shared epitope (SE) status were determined. Data were compared with 125 and 128 patients with anti-CCP-positive early arthritis and established RA respectively. RESULTS: In patients with anti-CCP-positive arthralgia, the frequency of SE allele positivity is significantly lower when compared with anti-CCP-positive early arthritis and established RA (58% vs 80%, and 58% vs 92%, respectively, both p<0.001). Median anti-CCP levels were higher in the group of patients with SE-positive arthralgia compared with the group of patients with SE-negative arthralgia (p = 0.02). Median anti-CCP levels were similar in the groups of patients with SE-positive arthralgia and arthritis. CONCLUSIONS: The lower frequency of SE positivity in patients with arthralgia compared with patients with RA indicates that, compared with patients who were SE positive, patients who were SE negative as a group go through a longer arthralgia phase, or alternatively have a lower risk for transition from anti-CCP positive arthralgia to RA. Furthermore, the present results suggest that in this early stage the effect of the SE on disease risk may be mediated through higher anti-CCP levels.

[Progressive partial lipodystrophy; an external problem with internal anomalies]. / Progressieve partiële lipodystrofie; een uiterlijk probleem met inwendige afwijkingen.

Progressive partial lipodystrophy (PPL) was diagnosed in two girls aged 6 and 8 years. PPL is characterized by loss of subcutaneous fat, starting in the face and progressing to trunk and arms. Diagnosis is based upon the cachectic appearance and the normal growth parameters. It is a rare disease of unknown aetiology, usually beginning in childhood and more frequent in females. An association with diabetes mellitus, hypertriglyceridaemia and glomerulonephritis has been described. Follow-up should be focused on these and on psychological effects. No causal therapy is available. The facial appearance can be restored by injection of liquid silicones. Life expectancy does not appear to be affected.

Bullous pemphigoid successfully controlled by tetracycline and nicotinamide.

In 1986, Berk and Lorincz reported the efficacy of tetracycline and nicotinamide in the treatment of bullous pemphigoid (BP). In the present study of seven patients with BP, we found that a regimen of 2 g tetracycline combined with 2 g nicotinamide daily was effective in clearing the skin lesions. Total remission was achieved within 6-8 weeks, after which the dose was gradually tapered. The mean duration of therapy was 7 months. No effect on the titre of antibasement membrane antibodies was observed. The mode of action of this therapy is unknown.