Treat-to-target recommendations in giant cell arteritis and polymyalgia rheumatica.

OBJECTIVES: To develop treat-to-target (T2T) recommendations in giant cell arteritis (GCA) and polymyalgia rheumatica (PMR). METHODS: A systematic literature review was conducted to retrieve data on treatment targets and outcomes in GCA/PMR as well as to identify the evidence for the effectiveness of a T2T-based management approach in these diseases. Based on evidence and expert opinion, the task force (29 participants from 10 countries consisting of physicians, a healthcare professional and a patient) developed recommendations, with consensus obtained through voting. The final level of agreement was provided anonymously. RESULTS: Five overarching principles and six-specific recommendations were formulated. Management of GCA and PMR should be based on shared decisions between patient and physician recognising the need for urgent treatment of GCA to avoid ischaemic complications, and it should aim at maximising health-related quality of life in both diseases. The treatment targets are achievement and maintenance of remission, as well as prevention of tissue ischaemia and vascular damage. Comorbidities need to be considered when assessing disease activity and selecting treatment. CONCLUSION: These are the first T2T recommendations for GCA and PMR. Treatment targets, as well as strategies to assess, achieve and maintain these targets have been defined. The research agenda highlights the gaps in evidence and the need for future research.

Evidence on treat to target strategies in polymyalgia rheumatica and giant cell arteritis: a systematic literature review.

OBJECTIVES: To inform an international task force about current evidence on Treat to Target (T2T) strategies in PMR and GCA. METHODS: A systematic literature research (SLR) was conducted in Medline, EMBASE, Cochrane Library, clinicaltrials.gov from their inception date to May 2022, and in the EULAR/ACR abstract database (2019-2021). Randomised clinical trials (RCTs) and non-randomised interventional studies published in English and answering at least one of the eleven PICO questions on T2T strategies, treatment targets and outcomes, framed by the taskforce, were identified. Study selection process, data extraction and risk of bias assessment were conducted independently by two investigators. RESULTS: Of 7809 screened abstracts, 397 were selected for detailed review and 76 manuscripts were finally included (31 RCTs, eight subgroup/exploratory analyses of RCTs and 37 non-randomised interventional studies). No study comparing a T2T strategy against standard of care was identified. In PMR RCTs, the most frequently applied outcomes concerned treatment (90.9% of RCTs), particularly the cumulative glucocorticoids (GC) dose and GC tapering, followed by clinical, laboratory and safety outcomes (63.3% each). Conversely, the most commonly reported outcomes in RCTs in GCA were prevention of relapses (72.2%), remission as well as treatment-related and safety outcomes (67.0% each). CONCLUSIONS: This SLR provides evidence and highlights the knowledge gaps on T2T strategies in PMR and GCA, informing the task force developing T2T recommendations for these diseases.

The provisional OMERACT ultrasonography score for giant cell arteritis.

OBJECTIVES: To develop an Outcome Measures in Rheumatology (OMERACT) ultrasonography score for monitoring disease activity in giant cell arteritis (GCA) and evaluate its metric properties. METHODS: The OMERACT Instrument Selection Algorithm was followed. Forty-nine members of the OMERACT ultrasonography large vessel vasculitis working group were invited to seven Delphi rounds. An online reliability exercise was conducted using images of bilateral common temporal arteries, parietal and frontal branches as well as axillary arteries from 16 patients with GCA and 7 controls. Sensitivity to change and convergent construct validity were tested using data from a prospective cohort of patients with new GCA in which ultrasound-based intima-media thickness (IMT) measurements were conducted at weeks 1, 3, 6, 12 and 24. RESULTS: Agreement was obtained (92.7%) for the OMERACT GCA Ultrasonography Score (OGUS), calculated as follows: sum of IMT measured in every segment divided by the rounded cut-off values of IMTs in each segment. The resulting value is then divided by the number of segments available. Thirty-five members conducted the reliability exercise, the interrater intraclass correlation coefficient (ICC) for the OGUS was 0.72-0.84 and the median intrareader ICC was 0.91. The prospective cohort consisted of 52 patients. Sensitivity to change between baseline and each follow-up visit up to week 24 yielded standardised mean differences from -1.19 to -2.16, corresponding to large and very large magnitudes of change, respectively. OGUS correlated moderately with erythrocyte sedimentation rate, C reactive protein and Birmingham Vasculitis Activity Score (corrcoeff 0.37-0.48). CONCLUSION: We developed a provisional OGUS for potential use in clinical trials.

Do statins decrease vascular inflammation in patients at risk for large-vessel vasculitis? A retrospective observational study with FDG-PET/CT in polymyalgia rheumatica, giant cell arteritis and fever of unknown origin.

OBJECTIVES: [18F] Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) can detect the presence of large-vessel vasculitis (LVV) in patients with polymyalgia rheumatica (PMR), giant cell arteritis (GCA) and fever of unknown origin (FUO). The aim of this study was to evaluate whether statins could reduce FDG-PET/CT-assessed vascular inflammation in this group of patients. METHODS: Clinical, demographic, laboratory data, current pharmacological treatments, and cardiovascular risk factors of patients with PMR, GCA and FUO, who underwent FDG-PET/CT, were recorded. FDG uptake was measured at prespecified arterial sites with the mean standardised uptake value (SUV), and with a qualitative visual score, summed up to obtain a total vascular score (TVS). LVV was diagnosed if arterial FDG visual uptake was equal or higher of liver uptake. RESULTS: 129 patients were included (96 with PMR, 16 with GCA, 13 with both PMR and GCA, and 4 with FUO), of whom 75 (58.1%) showed LVV. Twenty out of 129 (15.5%) patients were taking statins. TVS was significantly lower in patients treated with statins (p=0.02), especially in the aorta (p=0.023) and femoral arteries (p=0.027). CONCLUSIONS: Our preliminary results suggest that statins may exert a potential protective role on vascular inflammation in patients with PMR and GCA. Statin use could spuriously decrease FDG uptake of the vessel walls.

Long-Term Retention Rate of Tofacitinib in Rheumatoid Arthritis: An Italian Multicenter Retrospective Cohort Study.

Background: Tofacitinib (TOFA) was the first Janus kinase inhibitor (JAKi) to be approved for the treatment of rheumatoid arthritis (RA). However, data on the retention rate of TOFA therapy are still far from definitive. Objective: The goal of this study is to add new real-world data on the TOFA retention rate in a cohort of RA patients followed for a long period of time. Methods: A multicenter retrospective study of RA subjects treated with TOFA as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) was conducted in 23 Italian tertiary rheumatology centers. The study considered a treatment period of up to 48 months for all included patients. The TOFA retention rate was assessed with the Kaplan-Meier method. Hazard ratios (HRs) for TOFA discontinuation were obtained using Cox regression analysis. Results: We enrolled a total of 213 patients. Data analysis revealed that the TOFA retention rate was 86.5% (95% CI: 81.8-91.5%) at month 12, 78.8% (95% CI: 78.8-85.2%) at month 24, 63.8% (95% CI: 55.1-73.8%) at month 36, and 59.9% (95% CI: 55.1-73.8%) at month 48 after starting treatment. None of the factors analyzed, including the number of previous treatments received, disease activity or duration, presence of rheumatoid factor and/or anti-citrullinated protein antibody, and presence of comorbidities, were predictive of the TOFA retention rate. Safety data were comparable to those reported in the registration studies. Conclusions: TOFA demonstrated a long retention rate in RA in a real-world setting. This result, together with the safety data obtained, underscores that TOFA is a viable alternative for patients who have failed treatment with csDMARD and/or biologic DMARDs (bDMARDs). Further large, long-term observational studies are urgently needed to confirm these results.

Clinical and FDG-PET/CT correlates in patients with polymyalgia rheumatica.

OBJECTIVES: We aimed to evaluate joint and vessel uptake in patients with polymyalgia rheumatica (PMR) by FDG-PET and correlate it with clinical findings. METHODS: Consecutive PMR patients, without clinical signs of giant cell arteritis, underwent a standardised clinical examination and FDG-PET/CT. Controls were consecutive subjects undergoing FDG-PET for the suspicion of neoplasm not confirmed by the examination. Uptake was evaluated by a qualitative visual score, using the liver uptake as reference and by the semi-quantitative mean standardised uptake value (SUV) and target-to-background ratio (TBR) methods. RESULTS: Eighty-four patients and 84 controls (55 women, median age 73 years, range 50-92 years in both groups) were studied. Sixteen patients were taking glucocorticoids (GC). PMR patients showed a higher articular uptake than controls. GC-treated patients showed uptake lower than GC-naïve patients, but still higher than controls. PMR patients showed a higher vascular uptake than controls in all districts except in the carotid arteries, when evaluated by the visual score. Conversely, the semi-quantitative approach yielded no significant differences. Forty-two patients (50%) showed PET evidence of large-vessel vasculitis (LVV), defined as uptake ≥ than that of the liver, and 11.9% showed LVV with vascular uptake higher than that of the liver. The correlation between clinical findings and uptake was scarce. Neither clinical nor laboratory findings could predict the presence of LVV. CONCLUSIONS: Patients with PMR show a typical joint pattern at FDG-PET. There are no clinical or laboratory predictors of LVV. Imaging appears to be the only tool to assess LVV in these patients.

New insights into the role of imaging in polymyalgia rheumatica.

PMR is an inflammatory rheumatic disease of elderly people characterized by pain and stiffness in the neck, shoulder and pelvic girdles. No specific diagnostic confirmatory tests exist and clinical symptoms, as well as increased acute phase reactants, are unspecific. The diagnostic value of imaging including ultrasound, MRI and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) with/without CT for PMR is increasingly studied. These techniques, particularly FDG-PET/CT, may help to detect underlying GCA in PMR patients with an incomplete response to glucocorticoids and/or recurrent relapses. Recent imaging studies provide novel insights into the anatomical basis of inflammation in PMR, particularly at hip and spine, which may help to distinguish this disease from other mimicking conditions. In this review, we discuss novel insights into the pathoanatomy of PMR, compare the diagnostic values of different imaging techniques and summarize current data on the role of imaging for monitoring and outcome prediction.

Seasonal onset of polymyalgia rheumatica: correlations with the pattern of clinical presentation, disease severity and outcome in 383 patients from a single centre.

OBJECTIVES: Polymyalgia rheumatica (PMR) is an inflammatory disorder, more common in the elderly, characterised by girdle pain and stiffness, constitutional symptoms and raised serological markers of inflammation. Studies on the seasonality of onset of PMR have shown conflicting results, possibly due to the different diagnostic criteria and onset recognition. In this study, the month of onset of PMR was evaluated in patients originating from one geographical area, visited by the same clinician. METHODS: In 383 PMR patients (245 women, median age 73 years, range 47-92 years) examined between 1990 and 2014, PMR was diagnosed according to Bird's criteria. The month of onset was recorded systematically during the patient's interview. Clinical features initially recorded included the location of joint involvement, the coexistence of temporal arteritis (TA) or peripheral arthritis, and the type of onset (acute if reported of 72h or less). Patient follow-up, PMR severity and outcome were also recorded throughout the study. RESULTS: We failed to identify any peak month (p=0.93) or season (p=0.45) for the onset of PMR. Timing of onset did not correlate with the clinical features, severity or outcome of PMR. Only when patients were also affected by concomitant TA, the onset of PMR was more often seen in autumn (p=0.02). Patients with PMR onset in autumn also has a greater risk of developing TA during their follow-up (p=0.03). By multiple regression, the only outcome predicted by autumn onset was the use of methotrexate (p=0.039). CONCLUSIONS: PMR showed no seasonality of onset, except for the subset associated with TA. A risk factor with seasonal variation is suggested for the pathogenesis of this form of PMR.

Blood Biomarkers for Monitoring and Prognosis of Large Vessel Vasculitides.

PURPOSE OF REVIEW: Large vessel vasculitides (LVVs) are inflammatory conditions of the wall of large-sized arteries, mainly represented by giant cell arteritis (GCA) and Takayasu arteritis (TA). The inflammatory process within the vessel wall can lead to serious consequences such as development of aneurysms, strokes and blindness; therefore, early diagnosis and follow-up of LVV are fundamental. However, the arterial wall is poorly accessible and blood biomarkers are intended to help physicians not only in disease diagnosis but also in monitoring and defining the prognosis of these conditions, thus assisting therapeutic decisions and favouring personalised management. The field is the object of intense research as the identification of reliable biomarkers is likely to shed light on the mechanisms of disease progression and arterial remodelling. In this review, we will discuss the role of blood biomarkers in LVVs in the light of the latest evidence. RECENT FINDINGS: In clinical practice, the most widely performed laboratory investigations are the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). However, these indices may be within normal limits during disease relapse and they are not reliable in patients receiving interleukin-6 (IL-6) receptor inhibitors. New biomarkers struggle to gain traction in clinical practice and no molecule with good accuracy has been identified to date. IL-6, a pro-inflammatory cytokine that drives CRP synthesis and increases the ESR, is one of the most promising biomarkers in the field. IL-6 analysis is increasingly performed, and serum levels are more sensitive than ESR for active GCA and might reflect persistent inflammation with high risk of relapse in patients on IL-6 receptor inhibitors. A future with biomarkers that reflect different disease features is an important aspiration. Accordingly, intense effort is being made to identify IL-6-independent inflammatory biomarkers, such as S100 proteins, pentraxin-3 and osteopontin. Moreover, metalloproteinases such as MMP2/9 and angiogenic modulators such as VEGF, YLK-40 and angiopoietins are being studied as markers of arterial remodelling. Lastly, biomarkers indicating organ damage may guide prognostic stratification as well as emergency therapeutic decisions: the most promising biomarkers so far identified are NT-proBNP, which reflects myocardial strain; pentraxin-3, which has been associated with recent optic nerve ischemia; and endothelin-1, which is associated with ischaemic complications. Currently, the use of these molecules in clinical practice is limited because of their restricted availability, lack of sufficient studies supporting their validity and associated costs. Further evidence is required to better interpret their biological and clinical value.

Dissecting the inflammatory response in polymyalgia rheumatica: the relative role of IL-6 and its inhibition.

The efficacy of tocilizumab (TCZ), a monoclonal antibody to the interleukin (IL)-6 receptor, in suppressing disease activity in glucocorticoid-naïve patients with new-onset polymyalgia rheumatica (PMR) was studied. Its effect on a panel of cytokines and growth factors was evaluated. Three patients, fulfilling the PMR ACR/EULAR criteria, received TCZ at the dosage of 8 mg/kg every 4 weeks for three times followed by prednisone 0.2 mg/kg in case of inefficacy. Concentrations of IL-10, IL-6, tumour necrosis factor (TNF)-α, IL-1ß, IL-10, IL-17, interferon (IFN)-γ, vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and leukaemia inhibitory factor (LIF) were measured at baseline, after 72 h of the first TCZ infusion and then at weeks 1, 4, 5, 8, 9, 12, 13, 14, 16, and 22. A slight clinical improvement was seen only after the first TCZ infusion, but was largely inferior to that of conventional doses of GC administered subsequently. An ischaemic visual accident suggestive of GCA occurred in one patient during TCZ treatment. IL-6 was increased at baseline compared to controls, further increased after the first TCZ infusion, and was suppressed by GC. IL-17 production decreased during TCZ treatment and reverted to pre-treatment levels after GC. VEGF e PDGF showed a less constant pattern, but an increase of VEGF concentration antedated visual symptoms. The other cytokines were not detectable in patients and controls. In our small sample, TCZ was not able to suppress inflammation at the same degree as GC. As a result, monotherapy with TCZ in PMR cannot be recommended, although its efficacy as adjunctive treatment in GC-resistant patients should be further evaluated.

Ankylosis of the wrist bones in patients with rheumatoid arthritis: a study with extremity-dedicated MRI.

OBJECTIVES: Ankylosis, or spontaneous bone fusion, of the small joints of the hand is a rare event in patients with rheumatoid arthritis (RA), being observed in 0.8% of them on conventional radiographs. It is associated with long-lasting and severe disease. In other settings, such as fracture healing, bone fusion is a reparative process. The aim of this paper is the study of the frequency of wrist ankylosis in patients with RA in comparison with other arthritides; to correlate ankylosis with disease activity. METHODS: A total of 94 patients affected by RA, 71 patients with different rheumatic conditions and 42 controls with no joint disease or with slight hand osteoarthritis were studied. DAS-28 CRP was calculated in patients with RA and psoriatic arthritis. MRI of the clinically most involved wrist was performed with a 0.2 T, extremity-dedicated MRI system. RESULTS: Of RA patients, 10/94 (10.6%) showed ankylosis in comparison with 2/113 (1.8%) controls (p=0.015). RA patients with ankylosis had longer disease duration (p=0.019) but similar disease activity. CONCLUSIONS: MRI-defined bone ankylosis is frequent in RA. It is not limited to seronegative spondyloarthritides and may be part of the bone damage observed in RA.

Current evidence for therapeutic interventions and prognostic factors in polymyalgia rheumatica: a systematic literature review informing the 2015 European League Against Rheumatism/American College of Rheumatology recommendations for the management of polymyalgia rheumatica.

To summarise evidence on therapeutic interventions and prognostic factors in polymyalgia rheumatica (PMR). A systematic literature review was conducted using Ovid Medline, Embase, PubMed, CINAHL, Web of Science and the Cochrane Library (1970 through April 2014). Quality of evidence (QoE) of identified studies was appraised by Grading of Recommendations Assessment, Development and Evaluation (GRADE) (interventions) and the Quality In Prognosis Studies (QUIPS) methodologies (prognostic factors). Out of 10 931 titles identified, 52 articles were finally selected. A single study indicated that an initial prednisone dose of 20 mg/day is associated with a lower short-term relapse rate than 10 mg/day but at the cost of a higher rate of adverse events. Another study suggested a comparable efficacy of intramuscular methylprednisolone and oral glucocorticoids (GCs) with lower cumulative GC doses and less weight gain in the former group. Moderate to high QoE (1-2 studies) indicated a benefit of methotrexate in remission rates and cumulative GC doses in early PMR. Anti-tumour necrosis factor α agents are ineffective for PMR treatment. Among prognostic factors, female sex, high erythrocyte sedimentation rate (ESR) and peripheral arthritis were associated in some studies with a higher relapse risk. Women and patients with high ESR also appeared to have a longer duration of treatment. Several studies of varying quality, however, failed to prove these associations. In PMR, evidence for initial GC doses and subsequent tapering regimens is limited. Intramuscular methylprednisolone and methotrexate may be effective GC sparing agents. Female sex, high ESR and peripheral arthritis at disease outset are potential risk factors for a worse prognosis.

2015 Recommendations for the management of polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative.

Therapy for polymyalgia rheumatica (PMR) varies widely in clinical practice as international recommendations for PMR treatment are not currently available. In this paper, we report the 2015 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) recommendations for the management of PMR. We used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology as a framework for the project. Accordingly, the direction and strength of the recommendations are based on the quality of evidence, the balance between desirable and undesirable effects, patients' and clinicians' values and preferences, and resource use. Eight overarching principles and nine specific recommendations were developed covering several aspects of PMR, including basic and follow-up investigations of patients under treatment, risk factor assessment, medical access for patients and specialist referral, treatment strategies such as initial glucocorticoid (GC) doses and subsequent tapering regimens, use of intramuscular GCs and disease modifying anti-rheumatic drugs (DMARDs), as well as the roles of non-steroidal anti-rheumatic drugs and non-pharmacological interventions. These recommendations will inform primary, secondary and tertiary care physicians about an international consensus on the management of PMR. These recommendations should serve to inform clinicians about best practices in the care of patients with PMR.

Extrusion of the medial meniscus in knee osteoarthritis assessed with a rotating clino-orthostatic permanent-magnet MRI scanner.

PURPOSE: The objectives of this study were to assess the influence of weight-bearing on tibiofemoral osteoarthritis, including medial meniscal extrusion, by using a low-field (0.25 T) rotating clino-orthostatic permanent-magnet magnetic resonance (MR) scanner, and to analyse correlations of medial meniscal extrusion with the patient's Kellgren-Lawrence score, body mass index, and all the osteoarthritis features of the WORMS scoring system. MATERIALS AND METHODS: Twenty-six patients (69.2% women and 30.8% men; mean age 67 ± 9.7 years) with medial tibiofemoral knee osteoarthritis were prospectively enrolled and MR sequences were acquired in both clino- and orthostatic position. MR images were assessed by two independent radiologists, according to the WORMS scale. Medial meniscal extrusion was measured and its clino-orthostatic difference (∆MME) was calculated. RESULTS: Intra- and inter-observer agreement of the WORMS Global Score readings was high by Cohen's K test (>0.81). No significant clino-orthostatic changes in the scoring parameters of the medial tibiofemoral joint were shown by Wilcoxon's test. Medial meniscal extrusion measured on orthostatic images was significantly higher than that measured in clinostatic position (p < 0.0001). At univariate analysis, the Kellgren-Lawrence score, WORMS Global Score, cartilage loss, meniscal damage, and osteophytes were significantly correlated to ∆MME (p < 0.005). Using a multiple regression model, tibiofemoral cartilage loss was found to correlate independently with ∆MME (p = 0.0499). CONCLUSIONS: Medial meniscal extrusion, evaluated with an open-configuration, rotating MR scanner, increased from the clinostatic to the orthostatic position. ∆MME, a new meniscal parameter, correlated with several important features of medial tibiofemoral osteoarthritis.

Seronegative spondyloarthropathies: what radiologists should know.

Inflammatory involvement of the spine and sacroiliac joints is the most peculiar feature of seronegative spondyloarthropathies (SpA), which include ankylosing spondylitis, psoriatic arthritis, reactive arthritis (Reiter's syndrome), enteropathic spondylitis (related to inflammatory bowel diseases) and undifferentiated spondyloarthropathies. SAPHO syndrome may also be considered a SpA, but there is no clear agreement in this respect. Imaging, along with clinical and laboratory evaluation, is an important tool to reach a correct diagnosis and to provide a precise grading of disease progression, influencing both clinical management and therapy. Conventional radiography, which is often the first-step imaging modality in SpA, does not allow an early diagnosis. Computed tomography (CT) demonstrates with a very high spatial resolution the tiny structural alterations of cortical and spongy bone before they become evident on plain film radiographs. Magnetic resonance imaging (MRI) is the only modality that provides demonstration of bone marrow oedema, which reflects vasodilatation and inflammatory hyperaemia. The primary aim of this review article was to examine the involvement of the spine and sacroiliac joints in SpA using a multimodal radiological approach (radiography, CT, MRI), providing a practical guide for the differential diagnosis of these conditions.

Influence of Safety Warnings on the Prescribing Attitude of JAK Inhibitors for Rheumatoid Arthritis in Italy.

Background/Objectives: The Janus kinase inhibitors (JAKi) tofacitinib (TOFA), baricitinib (BARI), upadacitinib (UPA), and filgotinib (FILGO) are effective drugs for the treatment of rheumatoid arthritis. However, the US Food and Drug Administration (FDA) raised concerns about the safety of TOFA after its approval. This prompted the European Medicines Agency (EMA) to issue two safety warnings for limiting TOFA use, then extended a third warning to all JAKi in patients at high risk of developing serious adverse effects (SAE). These include thrombosis, major adverse cardiac events (MACE), and cancer. The purpose of this work was to analyze how the first two safety warnings from the EMA affected the prescribing of JAKi by rheumatologists in Italy. Methods: All patients with rheumatoid arthritis who had been prescribed JAKi for the first time in a 36-month period from 1 July 2019, to 30 June 2022 were considered. Data were obtained from the medical records of 29 Italian tertiary referral rheumatology centers. Patients were divided into three groups of 4 months each, depending on whether the JAKi prescription had occurred before the EMA's first safety alert (1 July-31 October 2019, Group 1), between the first and second alerts (1 November 2019-29 February 2020, Group 2), or between the second and third alerts (1 March 2021-30 June 2021, Group 3). The percentages and absolute changes in the patients prescribed the individual JAKi were analyzed. Differences among the three groups of patients regarding demographic and clinical characteristics were also assessed. Results: A total of 864 patients were prescribed a JAKi during the entire period considered. Of these, 343 were identified in Group 1, 233 in Group 2, and 288 in Group 3. An absolute reduction of 32% was observed in the number of patients prescribed a JAKi between Group 1 and Group 2 and 16% between Group 1 and Group 3. In contrast, there was a 19% increase in the prescription of a JAKi in patients between Group 2 and Group 3. In the first group, BARI was the most prescribed drug (227 prescriptions, 66.2% of the total), followed by TOFA (115, 33.5%) and UPA (1, 0.3%). In the second group, the most prescribed JAKi was BARI (147, 63.1%), followed by TOFA (65, 27.9%) and UPA (33, 11.5%). In the third group, BARI was still the most prescribed JAKi (104 prescriptions, 36.1%), followed by UPA (89, 30.9%), FILGO (89, 21.5%), and TOFA (33, 11.5%). The number of patients prescribed TOFA decreased significantly between Group 1 and Group 2 and between Group 2 and Group 3 (p ˂ 0.01). The number of patients who were prescribed BARI decreased significantly between Group 1 and Group 2 and between Group 2 and Group 3 (p ˂ 0.01). In contrast, the number of patients prescribed UPA increased between Group 2 and Group 3 (p ˂ 0.01). Conclusions: These data suggest that the warnings issued for TOFA were followed by a reduction in total JAKi prescriptions. However, the more selective JAKi (UPA and FILGO) were perceived by prescribers as favorable in terms of the risk/benefit ratio, and their use gradually increased at the expense of the other molecules.

High frequency of capsular knee involvement in polymyalgia rheumatica/giant cell arteritis patients studied by positron emission tomography.

OBJECTIVE: Peripheral arthritis has been described in up to 50% of PMR patients, with knee involvement in the majority. This study was designed to evaluate by PET/CT the knees of patients with PMR and GCA and to identify the knee structures involved by inflammation. METHODS: Twenty-five consecutive patients with PMR (19) or GCA (6) were studied in comparison with 25 age- and sex-matched controls who underwent PET/CT for initial staging of cancer. Clinical features, ESR and CRP were evaluated. Simultaneous FDG-PET and CT imaging from the skull base to the knee was performed after injection of 4.8-5.2 MBq of [(18)F]FDG per kilogram body weight. The knee anatomical structures being evaluated included joints, fibrous capsule, synovial recesses and bursae. RESULTS: At PET/CT, 21/25 patients (84%) showed bilateral diffuse uptake at the knees. The tracer clearly outlined the contour of the fibrous capsule. In 50 knees, 90% of capsular sites were involved by inflammation in comparison with 23% of intracapsular sites and 4.7% of extracapsular sites (P < 0.0001). No correlation was found between PET/CT results and ESR or CRP. FDG uptake, with a pattern similar to that observed in 96% of PMR/GCA patients, was seen in 20% of controls (P = 0.03). CONCLUSION: Our findings suggest that bilateral capsulitis of the knee is detectable in most PMR/GCA patients if a sensitive imaging technique such as PET/CT is used.