Tolerance and efficacy of targeted therapies prescribed for off-label indications in refractory systemic autoimmune diseases: data of the first 100 patients enrolled in the TATA registry (TArgeted Therapy in Autoimmune Diseases).

OBJECTIVES: To assess the tolerance and efficacy of targeted therapies prescribed off-label in refractory low-prevalence autoimmune and inflammatory systemic diseases. METHODS: The TATA registry (TArgeted Therapy in Autoimmune Diseases) is a prospective, observational, national and independent cohort follow-up. The inclusion criteria in the registry are as follows: age >18 years; low-prevalence autoimmune and inflammatory systemic disease treated with off-label drugs started after 1 January 2019. RESULTS: Hundred (100) patients (79 women) were enrolled. The median age was 52.5 years (95% CI 49 to 56) and the median disease duration before enrolment was 5 years (3 to 7). The targeted therapies at enrolment were as follows: Janus kinase/signal transducers and activators of transcription inhibitors (44%), anti-interleukin (IL)-6R (22%), anti-IL-12/23, anti-IL-23 and anti-IL-17 (9%), anti-B cell activating factor of the tumour necrosis factor family (5%), abatacept (5%), other targeted treatments (9%) and combination of targeted treatments (6%). 73% of patients were receiving corticosteroid therapy at enrolment (median dose 10 mg/day). The current median follow-up time is 9 months (8 to 10).Safety: 11 serious infections (incidence rate of 14.8/100 patient-years) and 1 cancer (1.3 cancers/100 patient-years) were observed. Two patients died from severe COVID-19 (2.7 deaths/100 patient-years).Efficacy: the targeted treatment was considered effective by the clinician in 56% of patients and allowed, in responders, a median reduction of oral corticosteroids of 15 (9 to 21) mg/day, below 7.5 mg/day in 76% of patients, while 28% discontinued. CONCLUSION: These initial results of the TATA registry confirm the diversity of targeted treatments prescribed off-label in refractory autoimmune diseases and their corticosteroid-sparing effect when effective. Tolerance was acceptable in these refractory patients with a long history of treatment with immunosuppressive drugs.

Ultrasonography and detection of subclinical joints and tendons involvements in Systemic Lupus erythematosus (SLE) patients: A cross-sectional multicenter study.

OBJECTIVES: The aims of this study in SLE population were (1) to describe ultrasonography (US) joint abnormalities, (2) to estimate the reliability of clinical swollen joint count (C-SJC) and SLEDAI (C-SLEDAI) versus US-SJC and US-SLEDAI scores, (3) to highlight specific patterns of lupus patients with Power Doppler (PD) abnormalities. METHOD: For this cross-sectional multicenter study, 151 consecutive adult SLE patients were recruited. Evaluation included a clinical standardized joint assessment, B-mode and PD US of 40 joints and 26 tendons blinded for clinical examination. Reliability and agreement between clinical and B-mode US were calculated using the intraclass correlation coefficients (ICC [95% Confidence Interval]). RESULTS: We found a very high frequency of subclinical US abnormalities in asymptomatic patients: 85% of patients without joint symptoms had at least 1 US abnormality. Among them 46 patients (87%) had a history of joint involvement. The most frequent abnormalities were joint effusmaions (108 patients), synovial hypertrophy (SH, 109 patients) and synovitis (61 patients). Joint or tendon PD signal (grade>1) was found in 44% of patients (67/151). Synovitis were mainly located especially on MCPs and wrists. Even if reliability between clinical and grey-scale US SJC assessments was poor, reliability between clinical and US SLEDAI was good. Comparison between SLE patients with and without PD signal did not show any specific SLE pattern. CONCLUSION: US may be useful to assess joint involvement in SLE patients but did not significantly change SLEDAI score.

Current role for radioisotope synovectomy.

Radioisotope synovectomy has been extensively used to treat patients with chronic inflammatory joint disease but has moved to a less prominent position since the introduction of new and highly effective drugs. Remaining indications are refractory synovitis, pigmented villonodular synovitis as an adjunct to surgery, and hemophilic arthropathy. The three main radioisotopes used are yttrium-90, rhenium-186, and erbium-189. Radioisotope synovectomy should be performed only by highly experienced professionals, to minimize the risk of injection-related complications. The available safety data, in particular regarding the risk of malignancy, are reassuring. The efficacy of yttrium-90 in chronic inflammatory joint disease remains controversial.

Decreased patient exposure to ionizing radiation during interventional rheumatology procedures after optimization of protection.

OBJECTIVES: To decrease radiation exposure of patients undergoing interventional rheumatology procedures, without adversely affecting quality of care. METHODS: The radiation dose received, assessed by the dose-area product (DAP), was measured during 283 intraarticular injections performed under fluoroscopic guidance between May and July 2013. Then, three steps were taken to decrease patients' radiation exposure: a copper filter was added, the anti-scatter grid was removed, and exposure cell sensitivity was set at the highest value. DAP was measured during 158 intraarticular injections performed in 2014 with these measures in place. RESULTS: Mean DAP before optimization was 175µGray·m2 during facet joint injections (n=4) and 43µGray·m2 during hip injections but was less than 20µGray·m2 for injections into the shoulders (15.7µGray·m2), ankles (7.7µGray·m2), wrists (3.7µGray·m2), and fingers (3.3µGray·m2). After optimization, DAP decreased markedly for all injection sites, by 52% (shoulders) to 87% (facet joints, 22.7µGray·m2). Decreases occurred at all three steps of the procedure, i.e., patient installation, injection, and last image hold. Exposure during facet joint injections varied from 84 (54.5-108.5) µGray·m2 when body mass index (BMI) was <25kg/m2 to 228.9 (161.3-340.4)µGray·m2 when BMI was>30kg/m2. CONCLUSION: Simple technical changes translate into large decreases in patient radiation exposure during fluoroscopically-guided injections, particularly at the facet joints and in obese patients.

Sjögren's syndrome complicated by interstitial cystitis: A case series and literature review.

OBJECTIVES: To characterize the interstitial cystitis (IC) associated with Sjögren's syndrome (SS). METHODS: Report of three new cases. Only cases fulfilling the American-European consensus criteria for SS and the European Society for the Study of Interstitial Cystitis criteria with positive histological findings for IC were included. RESULTS: Thirteen cases of SS and IC have been reported in women, including the three reported here, with a mean age of 54 years. SS appeared first in 77% (n=10) of cases, a mean of 6.6 years before IC. The symptoms of IC included pollakiuria (n=11), lower abdominal pain (n=8), urinary urgency (n=5), painful micturition (n=6), hematuria (n=3) and dysuria (n=3). Urinary dilatation occurred in three cases, leading to acute renal failure in two patients. The diagnosis of IC was confirmed by anatomical evidence of cystitis inflammation on bladder biopsy in all (n=13) patients. Treatment was reported for nine patients, seven of whom (78%) received corticosteroid treatment, which was partially or completely effective in six cases. Immunosuppressive treatment was added in three cases (cyclosporine, n=2; azathioprine, n=1; cyclophosphamide, n=1). Local bladder treatments were performed, with hydraulic distension in five cases and DMSO instillation in one patient. A urinary catheter was inserted in the two cases of acute obstructive renal failure. CONCLUSIONS: Urinary symptoms without infection should lead the physician to consider a diagnosis of IC in SS patients. Urinary dilatation may occur, leading to acute obstructive renal failure. Corticosteroid treatment may be effective and local treatments have been tried.

The learning curve of nurses for the assessment of swollen and tender joints in rheumatoid arthritis.

OBJECTIVES: In rheumatoid arthritis (RA), nurses are now increasingly involved in joint count assessment but training is not standardized. The aim was to evaluate and describe the learning curve of nurses for the assessment of swollen and tender joints in RA. METHOD: Twenty nurses from university rheumatology centres inexperienced with joint counts were allocated to a rheumatologist from their centre (teacher). Acquisition of skills consisted of Phase 1: (training), a centralized 4hour training session, with (a) lecture and demonstration, and (b) practical sessions on patients with their teachers, followed by Phase 2: (practice) involving further practice on 20 patients in their own hospitals. Primary outcome was achievement of adequate swollen joint agreement between nurse and their teacher ("gold standard") at the "joint" level defined by prevalence adjusted biased adjusted kappa (PABAK)>0.60. Agreement at the "patient" level of swollen joint count (SJC), tender joint count (TJC) as well as DAS28 between nurse and their teacher were assessed with intra-class correlation coefficients (ICC). RESULTS: During the training phase, 75% of nurses achieved a swollen joint PABAK>0.60 when compared with their teachers, which further improved to 89% after the 20 practice patients (Phase 2). Median swollen joint PABAK improved from 0.64 (Q1:Q3 0.55,0.86) to 0.83 (Q1:Q3 0.77,1) by the end of Phase 2. At the "patient" level, SJC agreement remained globally stable (ICC, 0.52 to 0.66), while TJC and DAS28 agreement remained excellent throughout. CONCLUSION: Nurses inexperienced in joint counts were able to achieve excellent agreement with their teachers in assessment of tender and swollen joints through a short training session; practice further enhanced this agreement. Larger longitudinal studies are required to assess skills retention.

Improving agreement in assessment of synovitis in rheumatoid arthritis.

OBJECTIVE: Synovitis assessment through evaluation of swollen joints is integral in steering treatment decisions in rheumatoid arthritis (RA). However, there is high inter-observer variation. The objective was to assess if a short collegiate consensus would improve swollen joint agreement between rheumatologists and whether this was affected by experience. METHODS: Eighteen rheumatologists from French university rheumatology units participated in three 30 minutes rounds over a half day meeting evaluating joint counts of RA patients in small groups, followed by short consensus discussions. Agreement was evaluated at the end of each round as follows: (i) global agreement of swollen joints (ii) swollen joint agreement according to level of experience of the rheumatologist (iii) swollen joint count and (iv) agreement of disease activity state according to the Disease Activity Score (DAS28). Agreement was calculated using percentage agreement and kappa. RESULTS: Global agreement of swollen joints failed to improve (kappa 0.50 to 0.52) at the joint level. Agreement between seniors did not improve but agreement between newly qualified rheumatologists and their senior peer, which was initially poor (kappa 0.28), improved significantly (to 0.54) at the end of the consensus exercises. Concordance of DAS28 activity states improved from 71% to 87%. CONCLUSION: Consensus exercises for swollen joint assessment is worthwhile and may potentially improve agreement between clinicians in clinical synovitis and disease activity state, benefit was mostly observed in newly qualified rheumatologists.

Information on glucocorticoid therapy in the main studies of biological agents.

OBJECTIVE: To evaluate reported information on prednisone therapy in the main studies of biological agents used to treat rheumatoid arthritis (RA). METHODS: We reviewed 66 publications (including four abstracts), including 11 studies of infliximab, 19 of etanercept, eight of adalimumab, five of golimumab, four of certolizumab, four of rituximab, eight of abatacept, and seven of tocilizumab. RESULTS: Whether concomitant prednisone therapy was used, it was specified in only 56 (85%) of the 66 publications. Only 42 (64%) publications indicated that the prednisone dosage remained unchanged throughout the study. The maximum prednisone dosage allowed was specified in only 39 (59%) reports and was lower than 8 mg/day in only four (6%) studies. Data enabling determination of the mean daily prednisone dosage in prednisone-treated patients was available for only eight (12%) studies; the mean dosage ranged from 5.0 to 9 mg/day (mean, 7.1 ± 1.5). The percentage of patients receiving prednisone therapy was reported for only 41 (62%) studies. All the above-mentioned information was available in only two (3%) study reports. The percentage of patients on prednisone therapy ranged from 34% to 93% (mean, 58 ± 13%) overall and varied across biological agents as follows: abatacept, 74.4%; golimumab, 67.9%; infliximab, 60.6%; certolizumab, 57.5%; rituximab, 57.5%; etanercept, 54.4%; tocilizumab, 52.8%; and adalimumab, 50.4%. These percentages did not decline between 1997 and 2010. CONCLUSION: Study reports provide inadequate information on prednisone therapy during biological treatment for RA.

Ultrasonography for diagnosing atypical gout. Two case reports.

Gout is characterized by the deposition of monosodium urate crystals on the surface of the articular cartilage, within periarticular tissues, and within bone and skin. The diagnosis rests on identification of the crystals in joint fluid or a tophus. However, joint aspiration is not always feasible, and the presentation may be atypical. We describe two cases of chronic gouty arthritis misdiagnosed as psoriatic arthritis. Ultrasonography of the bone and joints disclosed two patterns recently described as highly suggestive of gout, namely, the double-contour appearance of the cartilage and the snowstorm appearance of the synovial membrane. In addition, ultrasonography was useful for guided aspiration of joint fluid or other material containing monosodium urate crystals. Thus, ultrasonography may contribute to improve the diagnosis and treatment of gout.