Body Mass Index and response to rituximab in rheumatoid arthritis.

INTRODUCTION: Previous studies suggested that obesity could negatively affect the response to anti-TNFα agents, but data are lacking on how it affects the response to rituximab (RTX). We aimed to determine whether body mass index (BMI) is involved in the response to RTX in RA. METHODS: We retrospectively analyzed data for 114 RA patients receiving RTX. Change from baseline in DAS28, pain on a visual analog scale, erythrocyte sedimentation rate, C-reactive protein level, tender and swollen joint count was analyzed at 6 months. The primary outcome was decrease in DAS28 ≥ 1.2. Secondary outcomes were EULAR good response and remission. RESULTS: At baseline, the median [interquartile range] BMI was 26.8 [23.8-31.1] kg/m(2). The number of patients with normal weight, overweight and obesity was 38, 41 and 35, respectively. After 6 months, the number of RA patients with DAS28 decrease ≥ 1.2 and EULAR good response and remission was 44 (38.6%), 27 (23.7%) and 24 (21.1%), respectively. In univariate analysis, the median BMI was similar among responders and non-responders for DAS28 decrease ≥1.2 (26.9 [24.1-30.1] vs. 26.8 [23.2-31.6], P=0.78), EULAR good response (27.7 [24.3-30.7] vs. 26.7 [22.3-31.5], P=0.57) and remission (26.9 [24.1-30.8] vs. 26.8 [23.2-31.5], P=0.94). Adjusted multivariable analysis confirmed a lack of association between BMI and different responses measures to RTX. BMI was only negatively associated with decreased ΔSJC (P=0.0276) and ΔTJC (P=0.0233). CONCLUSION: BMI did not affect the response to RTX in RA. These data could help physicians to choose biologic agents for obese RA patients.

Body mass index and response to infliximab in rheumatoid arthritis.

OBJECTIVES: Excess adipose tissue in obese individuals may have immunomodulating properties and pharmacokinetics consequences. Previous studies have suggested that obesity could negatively affect the response to anti-TNF-α agents, notably infliximab (IFX). We aimed to determine whether body mass index (BMI) is involved in the response to IFX in rheumatoid arthritis (RA). METHODS: We retrospectively examined data for 76 RA patients receiving IFX. BMI was calculated before treatment, and change from baseline in DAS28, pain on a visual analog scale, erythrocyte sedimentation rate, C-reactive protein level, tender and swollen joint count was analysed at 6 months after treatment. The primary outcome was decrease in DAS28 ≥1.2. Secondary outcomes were good response and remission according to EULAR. RESULTS: At baseline, the median [interquartile range] BMI was 26.6 [22.6-30.6] kg/m2. The number of patients with normal weight, overweight and obesity was 25, 29 and 22. In multivariable analyses, IFX treated patients with lower BMI showed a more frequent DAS28 decrease ≥1.2 (25.5 [22.3-28.3] vs. 28.0 [23.2-32.5], p=0.02, odds ratio [OR] 0.88 [95% confidence interval 0.79-0.98]), EULAR good response (25.3 [21.9-27.5] vs. 27.5 [24.3-31.2], p=0.03, OR 0.87 [0.76-0.99]) and EULAR remission, although not significant (25.3 [21.9-26.4] vs. 27.5 [23.2-30.9], p=0.14, OR 0.88 [0.75-1.04]). CONCLUSIONS: Obesity may negatively influence the response to IFX in RA. These data could help physicians to choose biologic agents for obese RA patients.

Ultrasound in gout: a useful tool for following urate-lowering therapy.

OBJECTIVE: We aimed to determine the ability of ultrasonography (US) to show decrease or disappearance of urate deposits in gouty patients requiring urate-lowering therapy (ULT). METHODS: To be included in this prospective single-centre study, patients needed toexhibit (1) proven gout by monosodic urate (MSU) crystals in synovial fluid and (2) US-evidenced urate deposits (double contour [DC] sign and/or tophi) before starting ULT (allopurinol [n=4], febuxostat [n=12]). At baseline and after six months of ULT, one trained ultrasonographer assessed the knee and first metatarsophalangeal (MTP1s) joints. Serum uric-acid (SUA) level was assessed at baseline and at three and six months after ULT initiation. Correlation between US findings and achievement of SUA level objective (< 360µmol/L) was estimated by the kappa coefficient (κ). RESULTS: We studied 16 patients (all males, mean age 61.0±18.3 years). The mean disease duration was 7.1±6.2 years. Tophi were found at clinical examination in 56% of patients. Baseline SUA levels were 688±153µmol/L. At baseline, US revealed tophi or a DC sign among 62.5 to 75% of patients in knees and 87.5% in MTP1s. After six months of ULT, none of the four patients, not achieving the SUA level objective, had disappearance of US features. Among the remaining 12 patients, US features (tophi or DC sign) disappeared or decreased in all but one with a stable DC sign in one MTP1. The correlation between the whole US examination and SUA level was excellent (κ=0.875). CONCLUSIONS: US could show disappearance of urate deposits after ULT and appears to be well correlated with efficacy of ULT.

High anti-CCP antibody titres predict good response to rituximab in patients with active rheumatoid arthritis.

OBJECTIVE: Previous studies reported that anti-CCP antibody positivity predicts good response to rituximab (RTX) in rheumatoid arthritis (RA). A quantitative approach to such possibility could be a good way to detect the subset of patients most likely to respond. We investigated whether serum anti-CCP antibody titres could predict response to RTX in RA patients. METHODS: We retrospectively investigated RA patients who received RTX. The primary criterion was decrease in DAS28>1.2 at 6months (M6). Secondary efficacy criteria included a good response and remission according to EULAR. Predictors of response were investigated by multivariate logistic regression analysis. RESULTS: We included 114 RA patients (81.6% female, median age 53.5 [IQR 45.7-61.2] years, median disease duration 8.5 [4.0-16.0] years). Anti-CCP antibodies were present in 93 patients (81.6%), with median anti-CCP antibody titres 583 [195-1509] U/mL. In all, 44 patients (38.6%) showed decreased DAS28>1.2 at M6. On univariate analysis, high anti-CCP titres were associated with response rather than non-response to RTX (median 1122 [355-1755] vs. 386 [149-800] U/mL, P=0.0191) at M6. On multivariate regression analysis, with a cut-off of 1000 U/mL, anti-CCP antibody titres≥1000 was associated with a decrease in DAS28>1.2 (OR 5.10 [1.97-13.2], P=0.0002); a EULAR good response (4.26 [1.52-11.95], P=0.0059); and a trend for EULAR remission (2.52 [0.78-8.12], P=0.1207). CONCLUSION: High anti-CCP antibody titres predict response to RTX in RA. This factor, easily assessed in clinical practice, can help with personalized medicine and selecting the best candidates for RTX treatment.

Ultrasonography of shoulders in spondyloarthritis and rheumatoid arthritis: a case-control study.

INTRODUCTION: Shoulders are often involved in spondyloarthritis (SpA) and rheumatoid arthritis (RA). The diagnosis of peripheral SpA and its differential diagnosis with RA could be challenging. A recent ultrasound study showed that ultrasonography (US) of the hands might differentiate psoriatic arthritis to RA. The aim of the study was to compare different US features in SpA, RA and healthy controls. METHODS: A total of 38 SpA and 43 RA patients with clinical involvement of shoulders were included and compared to 33 controls. One blinded rheumatologist performed US examinations. The following items were assessed: gleno-humeral effusion, long-head biceps tendon tenosynovitis, subacromial and subdeltoid bursitis, acromio clavicular (AC) synovitis and humeral bone erosion. RESULTS: Thirty-eight SpA (mean age: 49.9 ± 15.4 years, 58% of male), 43 RA patients (52.9 ± 16.6 years, 26% of male) and 33 controls (55.2 ± 16.9 years, 42% of male) were assessed. In comparison to RA, SpA patients had higher frequency of AC synovitis (66% vs 5%, P < 0.0001) but lower prevalence of subacromial and subdeltoid bursitis (39% vs 67%, P = 0.015), gleno-humeral effusion (5% vs 28%, P = 0.008) and humeral bone erosion (10% vs 56%, P < 0.0001). Unilateral abnormalities were found more frequently in SpA patients than in RA (64% vs 26%, P < 0.0001). CONCLUSION: Our results suggest that AC synovitis is highly evocative of SpA in patients with inflammatory painful shoulders. Thus, US might help to diagnose SpA and to differentiate with RA.

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.

Three new cases of palmar fasciitis with polyarthritis including a patient with atypical mutilating osteolysis.

We managed three patients who had both palmar fasciitis and polyarthritis coexisting with gynecological malignancies. The first patient was followed up for 3 years, during which she experienced mutilating osteolysis of the fingers and very severe inflammation as assessed by osteoarticular ultrasonography. The second patient had active synovitis by ultrasonography without structural joint damage. Finally, in the last patient, magnetic resonance imaging showed synovitis and extensor tenosynovitis of the fingers. The many differential diagnoses of this paraneoplastic syndrome are discussed.

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.

Efficacy of anakinra in calcium pyrophosphate crystal-induced arthritis: a report of 16 cases and review of the literature.

OBJECTIVES: Calcium pyrophosphate (CPP) crystal-induced arthritis occurs particularly in elderly people. This population has frequently associated comorbidities and treatments, which could limit the use of conventional therapies (colchicine, non-steroidal anti-inflammatory drugs and corticosteroids). The aim of the study was to evaluate the efficacy and tolerance of anakinra in patients with CPP crystal-induced arthritis. METHODS: We performed a multicentric retrospective chart review of patients who received anakinra for CPP crystal-induced arthritis. Demographic information, comorbidities, co-prescription, short-term treatment outcomes, adverse event, complication and subsequent flares were reviewed. RESULTS: A total of 16 patients (12 females, mean age: 80.2±11.1 years) received anakinra (100 mg subcutaneously per day). The mean number of anakinra injection was 15.5±42.9 per patient (median: 3). All patients had contraindication and/or failure to conventional therapies. The majority (14 [87.5%]) of patients with CPP crystal-induced arthritis demonstrated a beneficial response to anakinra therapy: 10 good responses and four partial responses. A relapse occurred in six (37.5%) patients (mean time to relapse: 3.4±4.9 months). One patient had an acute bacterial pneumonitis. CONCLUSION: Our results suggest that anakinra is relatively well tolerated and could be a good option in the treatment of CPP crystal-induced arthritis, illustrating that IL-1ß blockade may be helpful to control flares in patients having CPP crystal-induced arthritis for which conventional therapies are ineffective or contra-indicated.

Efficacy of anakinra in gouty arthritis: a retrospective study of 40 cases.

INTRODUCTION: Gout is a common arthritis that occurs particularly in patients who frequently have associated comorbidities that limit the use of conventional therapies. The main mechanism of crystal-induced inflammation is interleukin-1 production by activation of the inflammasome. We aimed to evaluate the efficacy and tolerance of anakinra in gouty patients. METHODS: We conducted a multicenter retrospective review of patients receiving anakinra for gouty arthritis. We reviewed the response to treatment, adverse events and relapses. RESULTS: We examined data for 40 gouty patients (32 men; mean age 60.0 ± 13.9 years) receiving anakinra. Mean disease duration was 8.7 ± 8.7 years. All patients showed contraindications to and/or failure of at least two conventional therapies. Most (36; 90%) demonstrated good response to anakinra. Median pain on a 100-mm visual analog scale was rapidly decreased (73.5 (70.0 to 80.0) to 25.0 (20.0 to 32.5) mm, P < 0.0001), as was median C-reactive protein (CRP) level (130.5 (55.8 to 238.8) to 16.0 (5.0 to 29.5) mg/l, P < 0.0001). After a median follow-up of 7.0 (2.0 to 13.0) months, relapse occurred in 13 patients after a median delay of 15.0 (10.0 to 70.0) days. Seven infectious events, mainly with long-term use of anakinra, were noted. CONCLUSIONS: Anakinra may be efficient in gouty arthritis, is relatively well tolerated with short-term use, and could be a relevant option in managing gouty arthritis when conventional therapies are ineffective or contraindicated. Its long-term use could be limited by infectious complications.