2023 EULAR recommendations on imaging in diagnosis and management of crystal-induced arthropathies in clinical practice.

OBJECTIVE: To formulate evidence-based recommendations and overarching principles on the use of imaging in the clinical management of crystal-induced arthropathies (CiAs). METHODS: An international task force of 25 rheumatologists, radiologists, methodologists, healthcare professionals and patient research partners from 11 countries was formed according to the EULAR standard operating procedures. Fourteen key questions on the role of imaging in the most common forms of CiA were generated. The CiA assessed included gout, calcium pyrophosphate deposition disease and basic calcium phosphate deposition disease. Imaging modalities included conventional radiography, ultrasound, CT and MRI. Experts applied research evidence obtained from four systematic literature reviews using MEDLINE, EMBASE and CENTRAL. Task force members provided level of agreement (LoA) anonymously by using a Numerical Rating Scale from 0 to 10. RESULTS: Five overarching principles and 10 recommendations were developed encompassing the role of imaging in various aspects of patient management: making a diagnosis of CiA, monitoring inflammation and damage, predicting outcome, response to treatment, guided interventions and patient education. Overall, the LoA for the recommendations was high (8.46-9.92). CONCLUSIONS: These are the first recommendations that encompass the major forms of CiA and guide the use of common imaging modalities in this disease group in clinical practice.

A new ex vivo human model of osteoarthritis cartilage calcification.

OBJECTIVE: Cartilage pathologic calcification is a hallmark of osteoarthritis (OA). Here, we aimed to describe a new ex vivo human model to study the progression of cartilage calcification. METHOD: Cartilage explants (n = 11), as well as primary chondrocytes (n = 3), were obtained from OA patients undergoing knee replacement. Explants and chondrocytes were cultured in control (NT) or calcification (CM) medium (supplemented with ascorbic acid and ß-glycerophosphate). Calcification was evaluated by micro-CT scan at day 0 and 21 in explants, and by Alizarin red staining in chondrocyte monolayers. Raman spectrometry allowed characterization of the crystal type. Interleukin-6 (IL-6) secretion in explant and cell supernatants was measured by ELISA. Finally, matrix degradation was evaluated by Safranin-O staining of explant sections and by glycosaminoglycans (GAG) release in supernatants. RESULTS: Micro-CT scan showed calcifications in all explants at baseline (day 0), which in the CM group increased significantly in number and size after 21 days compared with the NT group. Raman spectrometry revealed that crystals were exclusively basic calcium phosphate crystals (carbonated hydroxyapatite) both in NT and CM. IL-6 secretion was significantly increased in calcifying conditions. Finally, CM significantly increased cartilage catabolism as assessed by decreased Safranin-O staining of tissue explants and increased GAG release in supernatants. CM effects (enhanced calcification, IL-6 secretion and proteoglycans turn-over) were recapitulated in vitro in OA chondrocytes. CONCLUSIONS: We have described a new ex vivo human model of cartilage calcification that can summurize the triad of events seen during osteoarthritis progression, i.e. calcification, inflammation, and cartilage degradation. This model will allow the identification of new anti-calcification compounds.

Are patients with gout with negative dual-energy computed tomography for monosodium urate crystal deposition easy-to-treat?

OBJECTIVES: To determine the clinical associations and predictive value of two thresholds of negative dual-energy CT (DECT) for MSU crystal deposition in gout patients initiating urate lowering therapy (ULT), and identify which threshold is more clinically relevant. METHODS: Patients from the CRYSTALILLE cohort with a diagnosis of gout naive to ULT with baseline DECT scans of knees and feet were selected. Two thresholds of positivity for DECT detection of MSU crystal deposition were considered (<0.01 cm3 and <0.1 cm3). Baseline characteristics and the prediction of key outcomes after ULT initiation including reaching serum urate (SU) levels <6.0 and 5.0 mg/dl and occurrence of flares at 6, 12 and 24 months, associated with both thresholds of negative DECTs were compared with those of. PATIENT: s having positive DECT scans. RESULTS: 211 patients aged 66.2 years [57; 75.8] with a symptom duration of 3 years [0; 7.8] were included. 38/211 (18%) and 90/211 (43%) had negative DECT scans for the 0.01 and 0.1 cm3 thresholds, respectively. Factors associated with negative DECT scans were younger age, shorter symptom duration, and absence of cardiovascular disease for both volume thresholds. 9/39 (23.1%), 3/26 (11.5%), and 1/18 (5.6%) of patients with <0.1 cm3 MSU crystals had flares at 6, 12 and 24 months, respectively, compared with 18/45 (40.0%), 9/36 (25.0%) and 2/18 (11.1%) patients with ≥0.1 cm3 (p> 0.05).Overall, 95 patients (68.3%) reached SU levels <6.0 mg/dl and 68 (48.9%) <5.0 mg/dl, without any difference between positive and negative DECTs, with ULT dosages which tended to be lower in patients with negative DECT. CONCLUSION: The 0.1 cm3 threshold was better correlated to clinical presentation and evolution than 0.01 cm3. Patients with gout with negative DECTs exhibit milder disease and a lower comorbidity burden. They do not exhibit particularly easy-to-treat hyperuricemia, but may have a lower risk of flares.

Retention, safety and efficacy of off-label conventional treatments and biologics for chronic calcium pyrophosphate crystal inflammatory arthritis.

OBJECTIVES: Very little is known on the efficacy and safety of drugs for the management of chronic calcium pyrophosphate (CPP) crystal inflammatory arthritis. The objectives of this work were to describe the drugs used in the management of chronic CPP crystal inflammatory arthritis in expert European centres, and to examine treatment retention. METHODS: This was a retrospective cohort study. Charts from patients with a diagnosis of persistent inflammatory and/or recurrent acute CPP crystal arthritis were reviewed in seven European centres. Baseline characteristics were collected, and visits at months 3, 6, 12 and 24 included an assessment of treatment response and safety. RESULTS: One hundred and ninety-four treatments were initiated in 129 patients. Colchicine (used first-line in n = 73/86), methotrexate (used first-line in n = 14/36), anakinra (n = 27) and tocilizumab (n = 25) were the most prescribed treatments, while long-term corticosteroids, hydroxychloroquine, canakinumab and sarilumab were used occasionally. The 24-month on-drug retention was higher for tocilizumab (40%) than anakinra (18.5%) (P < 0.05), while the difference between colchicine (29.1%) and methotrexate (44.4%) was not statistically significant (P = 0.10). Adverse events led to 14.1% of colchicine discontinuations (100% of diarrhoea), 4.3% for methotrexate, 31.8% for anakinra and 20% for tocilizumab; all other discontinuations were related to insufficient response or losses to follow-up. Efficacy outcomes did not differ significantly between treatments throughout follow-up. CONCLUSION: Daily colchicine is the first-line therapy used in chronic CPP crystal inflammatory arthritis, which is considered efficient in a third to half of cases. Second-line treatments include methotrexate and tocilizumab, which have higher retention than anakinra.

The 2023 ACR/EULAR classification criteria for calcium pyrophosphate deposition disease.

OBJECTIVE: Calcium pyrophosphate deposition (CPPD) disease is prevalent and has diverse presentations, but there are no validated classification criteria for this symptomatic arthritis. The American College of Rheumatology (ACR) and EULAR have developed the first-ever validated classification criteria for symptomatic CPPD disease. METHODS: Supported by the ACR and EULAR, a multinational group of investigators followed established methodology to develop these disease classification criteria. The group generated lists of candidate items and refined their definitions, collected de-identified patient profiles, evaluated strengths of associations between candidate items and CPPD disease, developed a classification criteria framework, and used multi-criterion decision analysis to define criteria weights and a classification threshold score. The criteria were validated in an independent cohort. RESULTS: Among patients with joint pain, swelling, or tenderness (entry criterion) whose symptoms are not fully explained by an alternative disease (exclusion criterion), the presence of crowned dens syndrome or calcium pyrophosphate crystals in synovial fluid are sufficient to classify a patient as having CPPD disease. In the absence of these findings, a score>56 points using weighted criteria, comprising clinical features, associated metabolic disorders, and results of laboratory and imaging investigations, can be used to classify as CPPD disease. These criteria had a sensitivity of 92.2% and specificity of 87.9% in the derivation cohort (190 CPPD cases, 148 mimickers), whereas sensitivity was 99.2% and specificity was 92.5% in the validation cohort (251 CPPD cases, 162 mimickers). CONCLUSION: The 2023 ACR/EULAR CPPD disease classification criteria have excellent performance characteristics and will facilitate research in this field.

Dual-energy computed tomography in crystalline arthritis: knowns and unknowns.

PURPOSE OF REVIEW: To give an overview of what can reasonably be considered as known about dual-energy computed tomography (DECT) in crystal-related arthropathies, and what still needs to be explored. RECENT FINDINGS: Recent studies suggest an overall superiority of DECT over ultrasound in gout in terms of sensitivity (89 vs. 84%) and specificity (91 vs. 84%), except in early disease. Additional studies are needed to optimize DECT postprocessing settings in order to improve the specificity of the technique and eliminate all artifacts. Evidence has been controversial concerning DECT's ability to detect monosodium urate (MSU) crystal deposits on vessel walls, or whether or not MSU-coded plaques are artifacts. DECT can be used to monitor MSU crystal depletion during urate-lowering treatment; MSU crystal volume is associated with cardiovascular risk and disease activity. There are some reports on calcium-containing crystal deposition diseases (calcium pyrophosphate and basic calcium phosphate) demonstrating that DECT can characterize and discriminate between the different types of crystals. SUMMARY: Our knowledge about the use of DECT in crystal-related arthropathies continues to expand. Some unknowns have been clarified but there's still lots to learn, particularly concerning gout management and the potential use of DECT in calcium-containing crystal-related arthropathies.

New-onset inflammatory bowel diseases among IL-17 inhibitor-treated patients: results from the case-control MISSIL study.

OBJECTIVES: To describe new-onset IBD (new IBD) in patients treated with IL-17 inhibitors (IL-17i), to assess their incidence and to identify their risk factors in real life. METHODS: A French national registry (MISSIL) aimed to report all cases of new IBD in patients treated with IL-17i from January 2016 to December 2019. Using the estimated number of patients treated by IL-17 in France during the study period, the annual incidence rates of new IBD was reported in IL-17i-treated patients. A case-control study was performed with two controls per new IBD case matched by gender, age and underlying inflammatory disease. RESULTS: Thirty-one cases of new IBD under IL-17i were collected: 27 patients treated for spondyloarthritis and four patients for psoriasis. All were observed with secukinumab (SEK). The median time to onset of new IBD symptoms was 4.0 (1.5-7.5) months. SEK was discontinued in all patients. The evolution was favourable with complete resolution (17/31), improvement (7/31) or stabilization (5/31). Two patients died: one due to a massive myocardial infarction and one due to post-colectomy complications. The incidence of new IBD decreased from 0.69/100 patient-years [PY] (7/1010) in 2016 to 0.08/100 PY (6/7951) in 2019. No previous treatment with etanercept (odds ratio [OR] = 0.33, 95% CI: 0.14-0.80, P = 0.014) and low number of previous biologic therapies (OR = 0.67, 95% CI: 0.47, 0.94, P = 0.021) were significantly associated with new IBD. CONCLUSION: The incidence of new IBD was low and decreased from 2016 to 2019. The outcome was favourable in 24 out of 31 patients, but two patients died.

Dual-energy computed tomography vs ultrasound, alone or combined, for the diagnosis of gout: a prospective study of accuracy.

OBJECTIVE: To examine the accuracy of dual-energy CT (DECT) vs ultrasound or their combination for the diagnosis of gout. METHODS: Using prospectively collected data from an outpatient rheumatology clinic at a tertiary-care hospital, we examined the diagnostic accuracy of either modality alone or their combination, by anatomical site (feet/ankles and/or knees), for the diagnosis of gout. We used two standards: (i) demonstration of monosodium urate crystals in synovial fluid (gold), and (ii) modified (excluding DECT and ultrasound) 2015 ACR-EULAR gout classification criteria (silver). RESULTS: Of the 147 patients who provided data, 48 (33%) had synovial fluid analysis performed (38 were monosodium urate-crystal positive) and mean symptom duration was 9.2 years. One hundred (68%) patients met the silver standard. Compared with the gold standard, diagnostic accuracy statistics for feet/ankles DECT, feet/ankles ultrasound, knees DECT and knees ultrasound were, respectively: sensitivity: 87%, 84%, 91% and 58%; specificity: 100%, 60%, 87% and 80%; positive predictive value: 100%, 89%, 97% and 92%; negative predictive value: 67%, 50%, 70% and 33%; area under the receiver operating characteristic curve: 0.93, 0.72, 0.89 and 0.66. Combining feet/ankles DECT with ultrasound or knees DECT with ultrasound led to a numerically higher sensitivity compared with DECT alone, but overall accuracy was lower. Similarly, combining imaging knees to feet/ankles also yielded a numerically higher sensitivity and negative predictive values compared with feet/ankles DECT alone, without differences in overall accuracy. Findings were replicated compared with the silver standard, but with lower numbers. CONCLUSIONS: Feet/ankles or knees DECT alone had the best overall accuracy for gout diagnosis. The DECT-US combination or multiple joint imaging offered no additional increase in overall diagnostic accuracy.

Crystal deposition measured with dual-energy computed tomography: association with mortality and cardiovascular risks in gout.

OBJECTIVES: To determine whether the volume of monosodium urate (MSU) crystal deposition measured with dual-energy CT (DECT) is predictive of short-term mortality and development of cardiovascular comorbidities and diabetes mellitus. METHODS: Patients with a diagnosis of gout having had baseline DECT scans of their knees and feet to measure the volume of MSU crystal deposition were included to undergo a follow-up visit. Risk factors for mortality and a composite variable (onset of any cardio-metabolic event) were examined using multivariable Cox models. RESULTS: A total of 128 patients aged 66.1 (14.0) years with gout durations of 11.4 (10.4) years were included; most were naïve of urate lowering therapy (61.7%), with a follow-up visit at 24 (12, 36) months. Baseline serum urate (SU) level was 7.44 (2.29) mg/dl and DECT volume of MSU crystals was 0.2 (0, 0.9) cm3. A total of 14 patients died during follow-up, 6/14 from a cardiovascular cause, and 17 patients presented a new cardio-metabolic comorbidity. Factors associated with mortality risk were baseline DECT volume of MSU crystals [hazard ratio (HR) 1.02, 95% CI: 1.002, 1.03] and baseline SU level (HR 1.04, 95% CI: 1.003, 1.06). DECT volume of MSU crystals was the only factor associated with the onset of cardio-metabolic comorbidities with a HR of 1.014 (95% CI: 1.001, 1.03). CONCLUSIONS: Volume of MSU crystals measured with DECT is a biomarker for the risk of developing new cardio-metabolic diseases and for all-cause mortality.

Utility of Ultrasound and Dual Energy CT in Crystal Disease Diagnosis and Management.

PURPOSE OF REVIEW: The objective of this review is to critically discuss the latest evidence on the use of ultrasound and dual energy computed tomography (DECT) for the assessment of microcrystalline arthritis. RECENT FINDINGS: Both techniques have been included in the classification and diagnostic criteria for gout, while only ultrasound appears in the diagnostic recommendations for CPPD. Regarding the management of the diseases, there is encouraging evidence for the use of both techniques for the follow-up of gout patients, while very few or null data are available for CPPD. Ultrasound has been adequately validated for the diagnosis of CPPD, while some issues have still to be clarified regarding gout. DECT has also demonstrated to be accurate for gout diagnosis, but very few data are available regarding CPPD. Future research should aim to improve the reliability of both techniques and to create scoring systems for a more accurate follow-up of patients.

Usefulness of a Visual Analog Scale for Measuring Anxiety in Hospitalized Patients Experiencing Pain: A Multicenter Cross-Sectional Study.

BACKGROUND: Anxiety is common in hospitalized patients and can worsen pain or lead to unsuccessful pain relief. AIMS: The purpose of this study was to evaluate the usefulness of measuring anxiety with a visual analog scale (VAS) in the hospitalized patient experiencing pain. DESIGN: We conducted a multiple-center cross-sectional study. PARTICIPANTS/SUBJECTS: Adult inpatients experiencing moderate to severe pain defined by a pain VAS score ≥40 of 100 were included. METHODS: Pain and anxiety data were collected using the following instruments: pain VAS, anxiety VAS, State Anxiety Scale of the Spielberger State-Trait Anxiety Inventory (STAI-YA) and Anxiety Subscale of the Hospital Anxiety and Depression Scale (HAD-A). RESULTS: Data were collected from 394 patients. Of those patients, 43.6% (171 of 392) and 36.6% (143 of 391) had significant anxiety according to STAI-Ya and HAD-A, respectively. Correlation was good between anxiety-VAS and STAI-YA (ρ = 0.67 [95% confidence interval 0.61-0.72]) and moderate between anxiety VAS and HAD-D (ρ = 0.48 [0.39-0.56]). The main factor predictive of situational anxiety was history of anxiety-depression symptoms (odds ratio = 2.95 [1.93-4.56]). For anxiety VAS score ≥ 40 of 100, the sensitivity for detecting anxiety was 81% with 70% specificity. CONCLUSION: This study confirmed the high prevalence of anxiety among inpatients experiencing pain, demonstrated the capacity of a VAS to assess this anxiety, determined an anxiety VAS cutoff level to screen for significant anxiety, and identified risk factors of anxiety in this population. Anxiety VAS has been found to be an easy-to-use method familiar to caregivers, with all the advantages needed for an effective screening instrument. An anxiety VAS score ≥40 of 100 would thus warrant particular attention to adapt care to the patient's anxiety-related pain and initiate specific therapeutic interventions.

Gout: state of the art after a decade of developments.

This review article summarizes the relevant English literature on gout from 2010 through April 2017. It emphasizes that the current epidemiology of gout indicates a rising prevalence worldwide, not only in Western countries but also in Southeast Asia, in close relationship with the obesity and metabolic syndrome epidemics. New pathogenic mechanisms of chronic hyperuricaemia focus on the gut (microbiota, ABCG2 expression) after the kidney. Cardiovascular and renal comorbidities are the key points to consider in terms of management. New imaging tools are available, including US with key features and dual-energy CT rendering it able to reveal deposits of urate crystals. These deposits are now included in new diagnostic and classification criteria. Overall, half of the patients with gout are readily treated with allopurinol, the recommended xanthine oxidase inhibitor (XOI), with prophylaxis for flares with low-dose daily colchicine. The main management issues are related to patient adherence, because gout patients have the lowest rate of medication possession ratio at 1 year, but they also include clinical inertia by physicians, meaning XOI dosage is not titrated according to regular serum uric acid level measurements for targeting serum uric acid levels for uncomplicated (6.0 mg/dl) and complicated gout, or the British Society for Rheumatology recommended target (5.0 mg/dl). Difficult-to-treat gout encompasses polyarticular flares, and mostly patients with comorbidities, renal or heart failure, leading to contraindications or side effects of standard-of-care drugs (colchicine, NSAIDs, oral steroids) for flares; and tophaceous and/or destructive arthropathies, leading to switching between XOIs (febuxostat) or to combining XOI and uricosurics.

Difficult-to-treat gout flares: eligibility for interleukin-1 inhibition in private practice is uncommon according to current EMA approval.

OBJECTIVE: The objective was to determine the proportion of patients with difficult-to-treat or difficult-to-prevent acute gout attacks eligible for IL-1 inhibition. METHODS: Participants included in the French cross-sectional GOSPEL cohort (n = 1003 gout patients) were examined for contraindications and intolerance to standard of care (SoC) drugs of gout flares (colchicine, non-steroidal anti-inflammatory drugs and systemic glucocorticoids). Patients were classified as definitely eligible for first-line IL-1 inhibition (canakinumab) according to European summary of product characteristics (contraindications/intolerance to SoC and at least three flares per year) without any other anti-inflammatory options (contraindications/intolerance only), or potentially eligible (precaution of use). Eligibility to receive IL-1 during an on-going flare related to insufficient efficacy was assessed (second-line eligibility). RESULTS: Definite first-line eligibility for IL-1 therapy was found in 10 patients (1%) and contraindication to all SoC therapies in nine patients who had presented <3 flares in the past 12 months. At least precaution of use for SoC therapies was noted for 218/1003 patients (21.7%). Of 487 patients experiencing flares at baseline, 114 (23.4%) were still experiencing pain scored ⩾4/10 numeric scale on day 3, one of whom could not receive further SoC drugs. Only nine of them had three or more flares in the past year and were eligible for second-line IL-1 inhibition. CONCLUSION: Despite significant numbers of patients without any SoC anti-inflammatory therapeutic options for gout flares, eligibility for IL-1 inhibition therapy according to current European approval is rare.

Abatacept Monotherapy Versus Abatacept Plus Methotrexate for Treatment-Refractory Rheumatoid Arthritis.

BACKGROUND: Methotrexate combination therapy improves abatacept efficacy as a first-line biologic agent for the treatment of rheumatoid arthritis, but it is unclear when abatacept is used later on, particularly after non-TNF inhibitor (TNFi) failure. STUDY QUESTION: The objective of this study was to determine whether treatment response after non-TNFi inadequate response is different in patients with rheumatoid arthritis (RA) treated with abatacept in combination with or not with methotrexate. METHODS: Patients treated with abatacept monotherapy or in combination with methotrexate after non-TNFi failure were included. RESULTS: Data from 46 patients aged 56 years [49-61] with 12 years [8-16] of disease duration were examined. Rituximab was the treatment used in the previous line for 75.0% of the combination therapy group (15/20) and 34.6% (9/26) in the monotherapy group. At 12 months, 38.5% (10/26) of patients were in good-to-moderate EULAR response in the monotherapy group compared with 25.0% (5/20) in the combination therapy group (P = 0.33). Treatment persistence at 12 months was 61.5% (16/26) in the monotherapy group and 35.0% (7/20) in the combination therapy group (P = 0.07). CONCLUSIONS: Adding methotrexate to abatacept did not improve treatment response in patients with RA after non-TNFi inadequate response.

Bone Samples Extracted from Embalmed Subjects Are Not Appropriate for the Assessment of Bone Quality at the Molecular Level Using Raman Spectroscopy.

Bone samples extracted from embalmed cadavers are commonly used as controls in the study of bone. The effects of embalmment on the molecular composition of bone are unknown. The objective of this study was to determine the effect of embalmment on the molecular composition and structure of bone, as evaluated by Raman spectroscopy. Bone samples of femoral heads from five embalmed donors and five fresh-frozen donors were compared using Raman microspectroscopy with DuoScan technology. Physicochemical parameters simultaneously describing the organic and mineral phases of bone were compared using the Mann-Whitney U test. Partial least squares discriminant analysis (PLS-DA) was used to determine specific Raman spectral features of each group. Study of the mineral phase showed a 15% reduction of the mineral-to-matrix ratio (p < 0.001), an 8% decrease of type B carbonate substitution (p < 0.001), and a 2% increase in crystallinity (p < 0.001) in the embalmed donors group compared to those of the fresh donors group. Regarding the organic phase of bone, the hydroxyproline-to-proline ratio was increased by 18% in the embalmed group (p < 0.001), with no variation in both the relative proteoglycan content (GAG/CH3) (p = 0.08) and collagen maturity (p = 0.57). PLS-DA showed that the embalmed group was characterized mainly by peaks assigned to hydroxyproline, lipids, and collagen. Embalmment induces significant modifications of the molecular composition of bone. Bone samples from embalmed subjects should be avoided as controls for Raman spectroscopy studies. Preservation procedures performed prior to bone sampling should be reported in studies using human cadaver samples.

Early-onset gout.

Early-onset gout (EOG) is characterized by the occurrence of the first symptoms of gout at an unusually young age, usually <40 years. The aim of this review is to provide an overview of the epidemiology, clinical presentation and prognosis, association with comorbidities and specific management of EOG. A particularly high proportion of patients with EOG come from ethnic groups with stronger genetic factors, such as populations in the Pacific and Taiwan, who therefore have the highest prevalence of gout overall. The clinical presentation and severity of gout are broadly similar between EOG and common gout, although a longer disease duration exacerbates the disease, which more often tends to become polyarticular. Patients suffering from EOG develop metabolic comorbidities commonly associated with gout earlier in life, although those tend to be less frequent at the time of diagnosis. Some international guidelines recommend early treatment of EOG patients with urate-lowering therapies.

Characteristics of difficult-to-treat axial spondyloarthritis: Results of a real-world multicentric study.

OBJECTIVE: The EULAR task force recently published the difficult-to-treat RA (D2T RA) definition, however, a definition of D2T axSpA is still lacking and limitations in this definition exist. The objectives were to study the characteristics of D2T axSpA patients using the EULAR definition and to study a subgroup of patients with a predefined more stringent definition including a temporal criterion. METHODS: A multicentric retrospective study was performed. D2T axSpA was defined as failure of≥2 b/tsDMARDs with different mechanism of action. Very D2T axSpA was defined as failure of≥2 b/tsDMARDs in less than 2 years of follow-up. D2T and Very D2T axSpA patients were compared to non-D2T (nD2T) axSpA patients. RESULTS: Three hundred and eleven axSpA patients were included: 88 D2T axSpA (28.3%) and 223 non-D2T (nD2T) axSpA (71.7%). Peripheral involvement was more prevalent in the D2T group (34.9 vs. 21.4%; P=0.015). BASDAI level at baseline was higher in the D2T group (63.7±16.5 vs. 58.8±14.7; P=0.015). Fibromyalgia was found to be more frequent in the D2T group vs nD2T group (P<0.001). Twelve patients (3.8%) were categorized as very D2T axSpA. Compared to nD2T, Very D2T patients had a higher CRP level at baseline (42.0±31.3 vs. 17.8±23.1; P=0.010). IBD prevalence at baseline was higher in the very D2T group (41.7 vs. 3.1%; P<0.001). None of the very D2T patients presented a fibromyalgia. CONCLUSION: D2T axSpA was associated with higher disease activity, peripheral involvement, extra-musculoskeletal manifestations and fibromyalgia. Very D2T patients represented a minim proportion of patients after applying a more stringent definition including a temporal criterion of 2 years and might be independent from fibromyalgia.