2023 EULAR classification criteria for hand osteoarthritis.

OBJECTIVES: The objective of this study is to develop classification criteria for overall hand osteoarthritis (OA), interphalangeal OA and thumb base OA based on self-reported data and radiographic features. METHODS: The classification criteria sets were developed in three phases. In phase 1, we identified criteria that discriminated hand OA from controls. In phase 2, we used a consensus-based decision analysis approach to derive a clinician-based evaluation of the relative importance of the criteria. In phase 3, we refined the scoring system, determined the cut-offs for disease classification and compared the sensitivity and specificity of the European Alliance of Associations for Rheumatology (EULAR) criteria with the 1990 American College of Rheumatology (ACR) criteria. RESULTS: In persons with hand symptoms and no other disease (including psoriasis) or acute injury that can explain the hand symptoms (mandatory criteria), hand OA can be classified based on age, duration of morning stiffness, number of joints with osteophytes and joint space narrowing, and concordance between symptoms and radiographic findings. Using a sum of scores based on each diagnostic element, overall hand OA can be classified if a person achieves 9 or more points on a 0-15 scale. The cut-off for interphalangeal OA and thumb base OA is 8 points. While the EULAR criteria demonstrated better sensitivity than the ACR criteria in the phase 1 data set, the performance of the two criteria sets was similar in two external cohorts. CONCLUSIONS: International experts developed the EULAR criteria to classify overall hand OA, interphalangeal OA and thumb base OA in clinical studies using a rigorous methodology.

Determination and characterization of patient subgroups based on pain trajectories in hand osteoarthritis.

OBJECTIVES: To investigate pain, pain trajectories and their determinants in hand osteoarthritis (OA). METHODS: Data from the HOSTAS (Hand OSTeoArthritis in Secondary care) consisting of consecutive hand OA patients were used. Australian Canadian Osteoarthritis Hand Index (AUSCAN) pain was measured yearly for four years. Patients with complete AUSCAN at ≥2 time points were eligible for longitudinal analysis. Associations between variables of interest and baseline AUSCAN pain were investigated with linear regression. Development of pain over time was modelled using latent class growth analysis (LCGA). Associations of LCGA classes with variables of interest were analysed using multinomial logistic regression adjusted for baseline pain. RESULTS: A total of 484/538 patients [mean (s.d.) age 60.8 (8.5) years, 86% women, mean (s.d.) AUSCAN pain 9.3 (4.3)] were eligible for longitudinal analysis. Sex, marital and working status, education, disease duration and severity, anxiety and depression scores, lower health-related quality of life (HR-QoL), specific illness perceptions and coping styles were associated with baseline pain. LCGA yielded three classes, characterized by average pain levels at baseline; average pain remained stable over time within classes. Classes with more pain were positively associated with BMI, tender joint count, symptom duration, hand function scores and depression scores, negatively with physical HR-QoL, and education level. CONCLUSION: Baseline pain was associated with patient and disease characteristics, and psychosocial factors. LCGA showed three pain trajectories in hand OA patients, with different baseline pain levels and stable pain over time. Classes were distinguished by BMI, education level, disease severity, depression and HR-QoL.

Serum biomarkers in prednisolone-treated hand osteoarthritis patients.

OBJECTIVES: To investigate whether biomarkers are modulated by prednisolone treatment in patients with hand OA and whether they can predict response to prednisolone. METHODS: Biomarkers reflecting tissue turnover and inflammation [aggrecanase-derived neoepitope of arggecan (ARGS), MMP-derived neoepitope of type I collagen (C1M), MMP-derived neoepitope of type III collagen (C3M), marker of true type V collagen formation (PROC5), MMP-derived neoepitope of CRP (CRPM), citrullinated vimentin fragment (VICM), high-sensitivity (hsCRP)] were measured in sera from 78 patients with painful inflammatory hand OA, who were randomized between prednisolone or placebo treatment. Association of baseline biomarker levels with disease characteristics [visual analogue scale (VAS) pain, synovial thickening ultrasonography sum score and erosive OA] and OMERACT-Osteoarthritis Research Society International (OARSI) response after 6 weeks were analysed with linear or logistic regression and adjusted for age, BMI and sex. Change in biomarker levels after 6 weeks was assessed with linear regression adjusted for baseline biomarker levels, age, BMI and sex. RESULTS: For all patients (mean age 64 years, 79% female), there were no associations between biomarker levels and VAS finger pain or synovial thickening score at baseline. Patients with erosive hand OA had higher levels of C1M and hsCRP [adjusted geometric mean ratio 1.24 (95% CI 1.03, 1.49) and 1.91 (1.19, 3.06), respectively]. Biomarker levels did not decrease over time. There was no association between baseline biomarkers levels and OARSI response, except for CRPM [geometric mean ratio of 0.88 (0.77, 1.00)]. CONCLUSION: Erosive disease was associated with higher levels of C1M and hsCRP. Biomarker levels were not influenced by treatment with prednisolone. Current biomarkers were not associated with response to prednisolone in hand OA.

Real-time vs static scoring in musculoskeletal ultrasonography in patients with inflammatory hand osteoarthritis.

OBJECTIVES: Agreement between real-time and static ultrasonography has not been studied in musculoskeletal diseases. We studied this agreement in inflammatory hand OA. METHODS: Ultrasonography was performed blinded to clinical information of 30 joints of 75 patients with hand OA, treated with prednisolone in a randomized placebo-controlled double-blind trial. Images were scored real-time at acquisition and stored images were scored static (paired in known chronological order) for inflammatory features and osteophytes (score 0-3). Agreement between methods was studied at joint level with quadratic weighted kappa. At patient level intra-class correlations (ICC) of sum scores and change in sum-scores (delta baseline-week 6) were calculated. Responsiveness of scoring methods was analysed with generalized estimating equations (GEE) with treatment as independent and ultrasonography findings as dependent variable. RESULTS: Agreement at baseline was good to excellent at joint level (kappa 0.72-0.88) and moderate to excellent at patient level (ICC 0.58-0.91). Agreement for change in sum scores was poor to fair for synovial thickening and effusion (ICC 0.18 and 0.34, respectively), while excellent for Doppler signal (ICC 0.80). Real-time ultrasonography discriminated between prednisolone and placebo with a mean between-group difference of synovial thickening of -2.5 (95% CI: -4.7, -0.3). Static ultrasonography did not show a decrease in synovial thickening. CONCLUSION: While cross-sectional agreement between real-time and static ultrasonography is good, static ultrasonography measurement of synovial thickening did not show responsiveness to prednisone therapy while real-time ultrasonography did. Therefore, when ultrasonography is used in clinical trials, real-time dynamic scoring should remain the standard for now.

Structural tissue damage and 24-month progression of semi-quantitative MRI biomarkers of knee osteoarthritis in the IMI-APPROACH cohort.

BACKGROUND: The IMI-APPROACH cohort is an exploratory, 5-centre, 2-year prospective follow-up study of knee osteoarthritis (OA). Aim was to describe baseline multi-tissue semiquantitative MRI evaluation of index knees and to describe change for different MRI features based on number of subregion-approaches and change in maximum grades over a 24-month period. METHODS: MRIs were acquired using 1.5 T or 3 T MRI systems and assessed using the semi-quantitative MRI OA Knee Scoring (MOAKS) system. MRIs were read at baseline and 24-months for cartilage damage, bone marrow lesions (BML), osteophytes, meniscal damage and extrusion, and Hoffa- and effusion-synovitis. In descriptive fashion, the frequencies of MRI features at baseline and change in these imaging biomarkers over time are presented for the entire sample in a subregional and maximum score approach for most features. Differences between knees without and with structural radiographic (R) OA are analyzed in addition. RESULTS: Two hundred eighty-nine participants had readable baseline MRI examinations. Mean age was 66.6 ± 7.1 years and participants had a mean BMI of 28.1 ± 5.3 kg/m2. The majority (55.3%) of included knees had radiographic OA. Any change in total cartilage MOAKS score was observed in 53.1% considering full-grade changes only, and in 73.9% including full-grade and within-grade changes. Any medial cartilage progression was seen in 23.9% and any lateral progression on 22.1%. While for the medial and lateral compartments numbers of subregions with improvement and worsening of BMLs were very similar, for the PFJ more improvement was observed compared to worsening (15.5% vs. 9.0%). Including within grade changes, the number of knees showing BML worsening increased from 42.2% to 55.6%. While for some features 24-months change was rare, frequency of change was much more common in knees with vs. without ROA (e.g. worsening of total MOAKS score cartilage in 68.4% of ROA knees vs. 36.7% of no-ROA knees, and 60.7% vs. 21.8% for an increase in maximum BML score per knee). CONCLUSIONS: A wide range of MRI-detected structural pathologies was present in the IMI-APPROACH cohort. Baseline prevalence and change of features was substantially more common in the ROA subgroup compared to the knees without ROA. TRIAL REGISTRATION: Clinicaltrials.gov identification: NCT03883568.

The management of hand osteoarthritis: The rheumatologist's perspective.

Hand osteoarthritis (OA) is treated by several medical professionals. In this review the rheumatologist's perspective will be conveyed. The rheumatologist tasks are to diagnose hand OA, exclude other causes of patient's complaints, and provide treatment. The rheumatologist therefore has a distinctive and important role in hand OA treatment. Although no disease modifying treatment exists, there are multiple options for managing hand OA in rheumatology practice, with the goal of achieving symptom relief and optimizing hand function. These treatments can be non-pharmacological or pharmacological. In this review we will provide a summary of evidence-based management options based on existing guidelines. Furthermore, we will describe common practice among rheumatologists for hand OA management. In order to do so, we performed a literature review of studies addressing treatment modality usage for hand OA. The review comprised 25 studies, which were heterogeneous in terms of treatment modality usage. In addition, a detailed description of care usage by patients in a Rheumatology outpatient clinic is given, based on data of our Hand OSTeoArthritis in Secondary care primary hand OA cohort. The large majority of these patients used any form of hand OA treatment (83%). Non-pharmacological treatment was less frequently used (47%) than pharmacological treatment (77%).

Anti-citrullinated protein antibodies acquire a pro-inflammatory Fc glycosylation phenotype prior to the onset of rheumatoid arthritis.

OBJECTIVE: To determine whether anticitrullinated protein antibodies (ACPA) exhibit specific changes in Fc glycosylation prior to the onset of arthritis. METHODS: Serum samples of patients with ACPA-positive arthralgia (n=183) were collected at baseline and at various time points of follow-up. 105 patients developed arthritis after a median of 12 months (IQR 6-24) and were classified as having either rheumatoid arthritis (RA, n=48) or undifferentiated arthritis (UA, n=57) based on the 1987 American College of Rheumatology (ACR) criteria. ACPA and total serum IgG were isolated by affinity purification and cleaved by trypsin. ACPA-IgG1 Fc-glycopeptides were subsequently analysed by nano-liquid chromatography mass spectrometry and compared to those of total IgG1. RESULTS: At baseline, ACPA-IgG1 and total IgG1 from arthralgia patients displayed similar Fc glycosylation patterns. By contrast, at the onset of arthritis, ACPA exhibited a decrease in galactose residues in RA patients, but not in UA patients. This decrease occurred around 3 months prior to diagnosis and was paralleled by an increase in systemic inflammation (erythrocyte sedimentation rate). Galactosylation of total IgG1 was also decreased in RA, but this did not precede the onset of arthritis. Interestingly, we additionally noted a higher degree of ACPA-IgG1 Fc core fucosylation at baseline as compared with total IgG1, which further increased prior to diagnosis. CONCLUSIONS: ACPA display significant changes in Fc galactosylation and fucosylation prior to the onset of RA. These changes towards a more pro-inflammatory phenotype could be involved in driving the disease process.

Anti-carbamylated protein (anti-CarP) antibodies precede the onset of rheumatoid arthritis.

OBJECTIVE: The presence of anti-citrullinated protein antibodies (ACPA) and IgM-rheumatoid factor (IgM-RF) years before the clinical diagnosis of rheumatoid arthritis (RA) suggests they are possibly involved in the pathogenic process underlying RA. In this study, we analysed whether anti-carbamylated protein (anti-CarP) antibodies, a novel autoantibody system against carbamylated proteins, can also be detected in healthy individuals before they developed RA. METHODS: Multiple sera from asymptomatic blood donors prior to the onset of their RA symptoms and sera from age-matched and sex-matched controls were tested for the presence of antibodies directed against carbamylated-fetal calf serum (Ca-FCS), carbamylated-fibrinogen (Ca-Fib), cyclic citrullinated-peptide 2 and IgM-RF. RESULTS: Anti-Ca-FCS and anti-Ca-Fib antibodies were each present in 27% and 38% of the last serum samples of blood donors prior to the diagnosis of RA. Both anti-Ca-FCS and anti-Ca-Fib antibodies could be detected many years before the onset of RA. Anti-CarP antibodies as well as ACPA are, on average, detected earlier than IgM-RF. CONCLUSIONS: In addition to ACPA and IgM-RF, also the newly identified anti-CarP antibodies appear many years before the diagnosis of RA.

Symptom complexes in patients with seropositive arthralgia and in patients newly diagnosed with rheumatoid arthritis: a qualitative exploration of symptom development.

OBJECTIVE: The aim of this study was to explore symptoms and symptom development during the earliest phases of RA in patients with seropositive arthralgia and patients newly diagnosed with RA. METHODS: Interviews were conducted with 15 seropositive patients (anti-CCP positive, and often with arthralgia) and 11 newly presenting RA patients [classified according to the 2010 ACR/European League Against Rheumatism (EULAR) criteria]. Feedback procedures shared the experiences of seropositive arthralgia patients with early RA patients and vice versa. Data were analysed using thematic analysis. RESULTS: Symptoms common to both groups included joint pain, psychological distress, muscle cramps, abnormal skin sensations, stiffness, loss of motor control, weakness, fatigue and sleeping difficulties. Also, patterns of symptom evolution and the order of symptom development were described. Seropositive arthralgia patients described pain as annoying, while RA patients described how the severity of pain intensified before diagnosis, to the point where symptoms were psychologically distressing. Patients with seropositive arthralgia described reddening of the skin and burning sensations that they felt were indicative of the onset of swelling. Intense pain appeared to precede the onset of swelling for those with RA, which was often palindromic and travelled between joints until it later became persistent. CONCLUSION: This study highlights the breadth of symptoms that constitute the earliest phases of RA. Further research is needed to develop measures of symptom patterns and clusters to allow the predictive utility of symptoms to be assessed and to allow the integration of aspects of the patient's history into evidence-based investigative and management algorithms for use in primary and secondary care.

Anti-carbamylated protein antibodies are present in arthralgia patients and predict the development of rheumatoid arthritis.

OBJECTIVE: Recently, we discovered a new autoantibody system in rheumatoid arthritis (RA): anti-carbamylated protein (anti-CarP) antibodies. These antibodies have value in predicting joint destruction; however, it is not clear whether they are present before the diagnosis of RA and whether they have value as predictors of RA development. Therefore, we studied whether anti-CarP antibodies are present in patients with arthralgia and whether their presence is associated with the development of RA. METHODS: Sera from 340 arthralgia patients who did not have clinical signs of arthritis but who were positive for IgM rheumatoid factor (IgM-RF) and/or anti-cyclic citrullinated peptide 2 (anti-CCP-2) and 32 healthy controls were tested for anti-CarP IgG antibodies. Of the patients with arthralgia, 111 were IgM-RF positive/anti-CCP-2 antibody negative and 229 were anti-CCP-2 antibody positive. Patients were observed for the development of RA (based on the 2010 American College of Rheumatology/European League Against Rheumatism classification criteria) during a median followup period of 36 months. Cox proportional hazards regression analysis was performed to compare the risk of developing RA between arthralgia patients who were positive for anti-CarP antibodies and those who were negative for anti-CarP antibodies during followup. RESULTS: Anti-CarP antibodies were present in the sera of 39% of the patients. One hundred twenty patients developed RA, after a median of 12 months (interquartile range [IQR] 6-24). The presence of anti-CarP antibodies was associated with the development of RA in the entire arthralgia cohort after correction for RF and anti-CCP-2 antibody status (hazard ratio 1.56 [95% confidence interval 1.06-2.29], P=0.023), as well as in the anti-CCP-2 antibody-positive subgroup (odds ratio 2.231 [95% confidence interval 1.31-3.79], P=0.003). CONCLUSION: Anti-CarP antibodies are present in patients with arthralgia, and their presence predicts the development of RA independent of anti-CCP-2 antibodies.

Validation of the SQUASH physical activity questionnaire using accelerometry: The NEO study.

Objective: To investigate the construct validity of the SQUASH (Short QUestionnaire to ASsess Health-enhancing physical activity). Design: This is a cross-sectional analysis using baseline measurements from middle-aged participants in the Netherlands Epidemiology of Obesity (NEO) study. The SQUASH consists of questions on eleven physical activities investigating days per week, average duration per day and intensity, leading to a summed score in Metabolic Equivalent of Task hours (MET h) per week. To assess convergent validity, a Spearman's rank correlation between SQUASH and ActiHeart was calculated. To assess extreme group validity, three groups expected to differ in SQUASH total physical activity outcome were compared. For discriminative validity, a Spearman's rank correlation between SQUASH physical activity and participant height was investigated. Results: SQUASH data were available for 6550 participants (mean age 56 years, 44% men, mean BMI 26.3, 15% with knee OA, 13% with hand OA). Median physical activity (interquartile range) was 118 (76; 154) MET h/week according to SQUASH and 75 (58; 99) according to ActiHeart. Convergent validity was weak (rho â€‹= â€‹0.20). For all three extreme group comparisons, a statistically significant difference was present. Discriminative validity was present (rho â€‹= â€‹0.01). Compared with the reference quintile, those with a discrepancy SQUASH â€‹> â€‹ActiHeart and SQUASH â€‹< â€‹ActiHeart were relatively younger and more often male. Conclusions: The construct validity of the SQUASH seems sub-optimal. Physical activity reported by the SQUASH was generally higher than reported by ActiHeart. Whether the differences between SQUASH and ActiHeart are e.g. due to different underlying domains, limitations to our study, or reflect true differences needs further investigation.

Severity and progression of structural hand OA is not associated with progression of structural knee OA: The IMI-APPROACH cohort.

Objective: To investigate whether structural hand OA or its progression is associated with structural knee OA progression after two years in a population with symptomatic knee OA. Methods: We used baseline and two-year follow-up data from the IMI-APPROACH cohort. Symptomatic hand and knee OA were defined using ACR criteria. Radiographs of hands and knees were scored semi-quantitatively for osteophytes and joint space narrowing (JSN) following the OARSI atlas, and Kellgren-Lawrence (KL) scale. Knee images were also scored quantitatively with the Knee Image Digital Analysis (KIDA). Progression was defined as change above the minimal detectable change on patient level, except for KIDA (most affected knee compartment level). With logistic regression analyses the severity or progression of hand OA was associated with knee OA progression. Results: In 221 participants (mean age 66, 77% women, mean BMI 27.7, 19% hand OA), OA progression occurred in 18%-28%, and 9%-38% in hands and knees respectively, depending on features. Baseline structural hand OA features were not significantly associated with knee OA progression, except for hand osteophytes with KIDA osteophytes progression (odds ratio (OR) 1.03, 95% confidence interval (CI) 1.01-1.06). Progression of structural hand OA features was not significantly associated with knee OA progression, except for hand osteophyte or JSN progression, which was significantly associated with knee osteophyte progression (OR 0.44, 95%CI 0.22-0.84 and OR 0.43, 95%CI 0.18-0.94, respectively), and hand osteophyte progression for knee JSN (OR 2.51, 95%CI 1.15-5.48). Conclusions: In patients with symptomatic knee OA, no consistent associations between baseline structural hand OA or hand OA progression and knee OA progression were shown.

The type I IFN signature as a biomarker of preclinical rheumatoid arthritis.

OBJECTIVES: To validate the presence and demonstrate the clinical value of the type I interferon (IFN)-signature during arthritis development. METHOD: In 115 seropositive arthralgia patients who were followed for the development of arthritis (Amsterdam Reade cohort), and 25 presymptomatic individuals who developed rheumatoid arthritis (RA) later, and 45 population-based controls (Northern Sweden cohort), the expression levels of 7 type I IFN response genes were determined with multiplex qPCR and an IFN-score was calculated. The diagnostic performance of the IFN-score was evaluated using Cox regression and Receiver Operating Characteristics (ROC)-curve analysis. RESULTS: In 44 of the 115 at-risk individuals (38%) from the Amsterdam Reade cohort, arthritis developed after a median period of 8 months (IQR 5-13). Stratification of these individuals based on the IFN-score revealed that 15 out of 25 IFN(high) individuals converted to arthritis, compared with 29 out of 90 IFN(low) individuals (p=0.011). In the Northern Sweden cohort, the level of the IFN-score was also significantly increased in presymptomatic individuals who developed RA compared with population-based controls (p=0.002). Cox regression analysis of the Amsterdam Reade cohort showed that the hazard ratio (HR) for development of arthritis was 2.38 (p=0.008) for IFN(high) at-risk individuals after correction for anticitrullinated protein antibodies (ACPA) and rheumatoid factor (RF). The ROC-curve area under the curve (AUC) for the IFN-score combined with ACPA and RF in the prediction of arthritis was 78.5% (p=0.0001, 95% CI 0.70 to 0.87). CONCLUSIONS: The results demonstrated clinical utility for the IFN-signature as a biomarker in the prediction of arthritis development.

Adalimumab elicits a restricted anti-idiotypic antibody response in autoimmune patients resulting in functional neutralisation.

OBJECTIVES: Millions of patients worldwide are treated with therapeutic monoclonal antibodies. These biological therapeutics can be immunogenic, resulting in anti-drug antibody formation which leads to loss of response. Fully human biological agents, such as the anti-tumour necrosis factor α (anti-TNFα) antibody adalimumab, are considered to be weakly immunogenic, but anti-adalimumab antibodies (AAA) were recently detected in more than half of treated patients with rheumatoid arthritis (RA) within 28 weeks of treatment. A study was undertaken to determine the mechanism by which AAA lead to loss of response. METHODS: The specificity of the repertoire of AAA was investigated in a cohort of 50 AAA-positive RA patients. Inhibition experiments using TNFα and patient-derived anti-adalimumab monoclonal antibodies were performed. RESULTS: The antibody response against adalimumab is highly restricted: Fab fragments of a single monoclonal antibody specific for the idiotype of adalimumab inhibited 98.65% (25th-75th percentiles: 98.25-99.90) of the total anti-adalimumab reactivity in serum from 50 AAA-positive patients. The anti-adalimumab response was confined to the TNFα binding region of adalimumab, thereby neutralising its therapeutic efficacy. In line with this restricted specificity, small immune complexes were found in the circulation of AAA-forming patients. CONCLUSIONS: The humoral immune response against adalimumab is highly restricted and limited to the idiotype of the therapeutic antibody. All antibodies result in functional neutralisation of the drug, thereby providing a mechanism by which AAA formation leads to clinical non-response.

Monoclonal anti-citrullinated protein antibodies selected on citrullinated fibrinogen have distinct targets with different cross-reactivity patterns.

OBJECTIVE: ACPAs are thought to play a pathogenic role in RA. Because of their polyclonal nature it is difficult to study characteristics of ACPAs such as cross-reactivity or affinity. This study aimed to analyse the ACPA response at clonal level. METHODS: Citrullinated fibrinogen-specific B cells were isolated from blood derived from an RA patient by fluorescent automated cell sorting (FACS). Antigen specificity was verified by ELISA of culture supernatant. RNA of antigen-specific B cells was isolated and VH and VL chains were cloned and subsequently expressed as IgG1 antibodies. RESULTS: Two human recombinant antibodies were obtained that bind to citrullinated fibrinogen peptide (cFib). Both monoclonal antibodies originate from different naive B cells, undergo extensive somatic hypermutation and bind to cFib (but not to Fib) with moderate avidity. Furthermore, they show distinct cross-reactivity patterns towards other citrullinated peptides, suggesting that both antibodies have different primary targets. CONCLUSION: Together these data suggest that ACPAs are formed by antigen-driven maturation, and that multiple citrullinated antigens are involved in activating the B-cell response.

Patients with clinically diagnosed hand OA not fulfilling the ACR classification criteria are in an earlier disease phase and more often have thumb base OA.

Objective: To investigate the performance of the American College of Rheumatology (ACR) classification criteria for hand osteoarthritis. Design: Longitudinal data up to four years from a cohort of consecutive patients with primary hand osteoarthritis diagnosed by their rheumatologist (Hostas study) were used to classify presence or absence of hand osteoarthritis according to the 1990 ACR criteria (traditional format: one major and 4 minor ACR criteria) (ACR+/ACR-). Demographics, Australian/Canadian osteoarthritis hand index (AUSCAN) pain and function were obtained. Hand radiographs were scored according to Kellgren-Lawrence; radiographic osteoarthritis was defined as Kellgren-Lawrence ≥2 in ≥1 CMC1 joint or ≥2 DIP/PIP/MCP joints. Results: Of 538 patients (mean age 61 years, 86.1% women) 485 (90.1%) fulfilled ACR criteria at baseline. Except for the minor criterion swelling of <3 MCP joints, all criteria differed between the groups. ACR- patients were younger, with higher BMI, a shorter time since diagnosis, and less bony enlargements, joint deformities and radiographic osteoarthritis, except for radiographic CMC1 osteoarthritis which was seen more often in ACR- patients. No difference in AUSCAN pain or function was seen between ACR- versus ACR+ patients. After follow-up 37/53 (69.8%) converted to ACR+, 2/53 (3.8%) did not, and 14/53 (26.4%) were lost to follow-up. Conclusions: In clinical practice the majority of patients fulfill the ACR classification criteria, but those in an earlier disease phase, with less signs of hand osteoarthritis or with primarily thumb base osteoarthritis are less likely to fulfill them. New classification criteria also including earlier disease stages and with attention for hand osteoarthritis subtypes are required.

Surgical denervation as a treatment strategy for pain in hand osteoarthritis: a systematic literature review.

OBJECTIVE: Surgical denervation has been proposed as a treatment for pain in hand osteoarthritis (OA). This review aimed to summarise the available evidence and to propose a research agenda. METHODS: A systematic literature search was performed up to September 2022. Two investigators independently identified studies that reported on denervation for OA of the proximal interphalangeal, distal interphalangeal, metacarpophalangeal or carpometacarpal joints. Quality of studies was assessed and study characteristics, patient characteristics, details of the surgical technique and outcomes of the surgery were extracted. RESULTS: Of 169 references, 17 articles reporting on 384 denervations in 351 patients were selected. Sixteen case series reported positive outcomes with respect to pain, function and patient satisfaction. One non-randomised clinical trial reported no difference in outcome when comparing denervation of the first carpometacarpal (CMC I) joint to trapeziectomy. Adverse events were frequent, with sensory abnormalities occurring the most, followed by the need for revision surgery. All studies had significant risk of bias. CONCLUSION: Surgical denervation for pain in hand OA shows some promise, but the available evidence does not allow any conclusions of efficacy and higher-quality research is needed. Techniques should be harmonised and more data regarding how denervation compares to current usual care, other denervation methods or placebo in terms of outcomes and adverse events are needed.

Development of the anti-citrullinated protein antibody repertoire prior to the onset of rheumatoid arthritis.

OBJECTIVE: To examine how anti-citrullinated protein antibody (ACPA) epitope spreading takes place prior to the onset of clinical rheumatoid arthritis (RA), and to analyze the pattern of autoantigen reactivity at the beginning of the immune response. METHODS: Multiple consecutive serum samples from 79 RA patients who had donated blood before disease onset were available for analysis. Fifty-three patients tested positive for ACPAs prior to the onset of clinical RA. For these patients, a median of 6 (interquartile range 4-9) sequential pre-RA serum samples obtained 1-2 years apart were tested. Reactivity to 5 distinct citrullinated peptides was measured by enzyme-linked immunosorbent assay. Two peptides were derived from fibrinogen, 1 from vimentin, 1 from α-enolase, and 1 from filaggrin. RESULTS: In 25 of 53 ACPA-positive patients, seroconversion from ACPA absence to ACPA presence was observed. In 72% of these patients, the immune response started with reactivity to 1 peptide, without preference for a particular peptide. The number of peptides recognized increased over time, without a dominant epitope-spreading pattern. ACPAs appeared in low levels several years prior to the diagnosis of RA. Antibody titers increased markedly ∼2-4 years before diagnosis. CONCLUSION: Our findings indicate that ACPA epitope spreading occurs over several years prior to the onset of clinical RA. The initial autoimmune response is mostly directed toward only 1 autoantigen, but this is not always the same antigen. The marked increase in ACPA titers a few years prior to the diagnosis of RA suggests a second stage in disease development, which might be due to a variety of factors.

Neuropathic-like pain symptoms in inflammatory hand osteoarthritis lower quality of life and may not decrease under prednisolone treatment.

BACKGROUND: Pain is common in hand osteoarthritis (OA) and multiple types may occur. We investigated the prevalence, associated patient characteristics, influence on health-related quality of life (HR-QoL) and response to anti-inflammatory treatment of neuropathic-like pain in inflammatory hand OA. METHODS: Data were analysed from a 6-week, randomized, double-blind, placebo-controlled trial investigating prednisolone treatment in 92 patients with painful inflammatory hand OA. Neuropathic-like pain was measured with the painDETECT questionnaire. Associations between baseline characteristics and baseline neuropathic-like pain were analysed with ordinal logistic regression, association of baseline neuropathic-like pain symptoms with baseline HR-QoL with linear regression, painDETECT and visual analogue scale (VAS) change from baseline to week 6 and interaction of painDETECT with prednisolone efficacy on VAS pain change from baseline to week 6 with generalized estimating equations (GEE). RESULTS: Of 91 patients (79% female, mean age 64) with complete painDETECT data at baseline, 53% were unlikely to have neuropathic-like pain, 31% were indeterminate and 16% were likely to have neuropathic-like pain. Neuropathic-like pain was associated with female sex, less radiographic damage and more comorbidities. Patients with neuropathic-like pain had lower HR-QoL (PCS-6.5 [95% CI -10.4 to -2.6]) than those without. Neuropathic-like pain symptoms remained under prednisolone treatment and no interaction was seen between painDETECT and prednisolone efficacy on VAS pain. CONCLUSIONS: In this study, 16% of inflammatory hand OA patients had neuropathic-like pain. They were more often female, had more comorbidities and had lower QoL than those without. Neuropathic-like pain symptoms remained despite prednisolone treatment and did not seem to affect the outcome of prednisolone treatment. SIGNIFICANCE: Pain is the dominant symptom in hand OA, with an unclear aetiology. In this study, we found that neuropathic-like pain may play a role in hand OA, that it showed associations with female sex, younger age and more comorbidities and that it lowered health-related quality of life in hand OA. Neuropathic-like pain in hand OA seems resistant to prednisolone therapy but did not seem to interfere with the treatment of inflammatory pain with prednisolone.