A randomized prospective open-label controlled trial comparing the performance of a connected monitoring interface versus physical routine monitoring in patients with rheumatoid arthritis.

OBJECTIVES: In RA, telemedicine may allow tight control of disease activity while reducing hospital visits. We developed a smartphone application connected with a physician's interface to monitor RA patients. We aimed to assess the performance of this e-Health solution in comparison with routine practice in the management of patients with RA. METHODS: A six-month pragmatic, randomized, controlled, prospective, clinical trial was conducted in RA patients with high to moderate disease activity starting a new DMARD therapy. Two groups were established: 'connected monitoring' and 'conventional monitoring'. The primary outcome was the number of physical visits between baseline and six months. Secondary outcomes included adherence, satisfaction, changes in clinical, functional and health status scores (Short-Form 12). RESULTS: Of the 94 randomized patients, 89 completed study: 44 in the 'conventional monitoring' arm and 45 in the 'connected monitoring' arm. The total number of physical visits between required baseline and six-month visits was significantly lower in the 'connected monitoring' group [0.42 (0.58) vs 1.93 (0.55); P <0.05]. No differences between groups were observed in the clinical and functional scores. A better quality of life for Short-Form 12 subscores (Role-Physical and Role-Emotional) were found in the 'connected monitoring' group. CONCLUSION: Our results suggest that connected monitoring reduces the number of physical visits while maintaining a tight control of disease activity and improving quality of life in patients with RA starting a new treatment. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT03005925.

Successful long-term remission through tapering tocilizumab infusions: a single-center prospective study.

BACKGROUND: Strategic drug therapy for rheumatoid arthritis (RA) patients with prolonged remission is not well defined. According to recent guidelines, tapering biological Disease-Modifying Anti-Rheumatic Drugs (bDMARDs) may be considered. We aimed to evaluate the effectiveness of long-term maintenance of tocilizumab (TCZ) treatment after the progressive tapering of infusions. METHODS: We conducted an exploratory, prospective, single-center, open-label study, on RA patients with sustained remission of at least 3 months and treated with TCZ infusions every 4 weeks. The initial re-treatment interval was extended to 6 weeks for the first 3 months. Thereafter, the spacing between infusions was determined by the clinician. Successful long-term maintenance following the tapering of TCZ infusions was defined by patients still treated after two years by TCZ with a minimum dosing interval of 5 weeks. RESULTS: Thirteen patients were enrolled in the study. Eight out of thirteen were still treated by TCZ after two years. Successful long-term maintenance was possible in six patients, with four patients maintaining a re-treatment interval of 8-weeks or more. We observed 5 patients with TCZ withdrawal: one showing adverse drug reaction (neutropenia) and four with secondary failure. Patients achieving successful long-term maintenance with TCZ were significantly younger than those with secondary failure (p < 0.05). In addition, RA patients with positive rheumatoid factor and anti-citrullinated peptide antibodies, experienced a significantly greater number of flares during our 2-year follow-up (p < 0.01). CONCLUSIONS: A progressive tapering of TCZ infusions may be possible for many patients. However, larger studies, including more patients, are needed to confirm this therapeutic option. TRIAL REGISTRATION: NCT02909998. Date of registration: October 2008.

Biologic Disease-modifying Antirheumatic Drug (bDMARD)-induced Neutropenia: A Registry from a Retrospective Cohort of Patients with Rheumatic Diseases Treated with 3 Classes of Intravenous bDMARD.

OBJECTIVE: To examine the rate, risks factors, and consequences of neutropenia induced by intravenous (IV) biologic disease-modifying antirheumatic drugs (bDMARD). METHODS: We conducted a retrospective cohort study in 499 patients with rheumatic diseases treated by IV abatacept (ABA), infliximab (IFX), or tocilizumab (TCZ). RESULTS: Rheumatoid arthritis (RA) was the most frequent diagnosis (72%). Fifty-two patients (10.4%) experienced at least 1 episode of neutropenia. No episodes of grade 4 neutropenia were documented. TCZ was more frequently related to neutropenia than ABA or IFX (18.6% vs 3.8% and 2.8%, respectively, p < 0.001). The following factors were identified as predictors of experiencing neutropenia with IV bDMARD: history of neutropenia with methotrexate (MTX; synthetic DMARD; OR 1.56, 95% CI 1.17-7.14), concomitant treatment by MTX (OR 1.21, 95% CI 1.01-2.64), and TCZ treatment (OR 2.72, 95% CI 1.53-9.05). Patients experiencing a TCZ-induced neutropenia did not show a higher risk of severe infections; however, this group had a shorter drug survival (9 mos vs 20 mos, p < 0.02) compared with TCZ patients without neutropenia. CONCLUSION: Among 3 different classes of IV bDMARD, TCZ is associated with the higher risk of neutropenia. No increased frequency of infection episodes was documented in this group.

Association of TRAF1-C5 with risk of uveitis in juvenile idiopathic arthritis.

OBJECTIVES: Numerous single nucleotide polymorphisms (SNPs) have been associated with JIA, but few of these studies were replicated. We conducted a candidate-gene approach study to assess if some SNPs could be related to clinical subtypes or other clinical features of the juvenile idiopathic arthritis (JIA) such as the risk of uveitis, ANA positivity and the age at onset. METHODS: SNPs in six genes were analysed: PTPN22, STAT4, TRAF1-C5, TGFbeta, TNFAIP3, and C12orf30. We retrospectively included 104 JIA patients, fulfilling the ILAR classification criteria. Association between SNPs and JIA clinical subtypes, the presence of ANA, risk of uveitis and age at onset was evaluated using a Chi2 test or a Fischer test. RESULTS: No associations between different clinical subtypes as well as presence of ANA and the 6 SNPs were found. However, the AA genotype of TRAF1-C5 appeared associated in a subgroup of patients with uveitis in oligoarticular and polyarticular forms [OR 3.77 (95% CI: 1.1067, 12.8527); P=0.066]. Furthermore, AA TRAF1-C5 was significantly more frequent in antinuclear antibodies (ANA) positive patients presenting uveitis, compared to patients without uveitis and without ANA (P<0.05). CONCLUSION: TRAF1-C5 genotype could identify JIA patients with a risk to develop uveitis especially in oligo and polyarticular forms and among ANA-positive children. Given the moderate size of our cohort, this association has to be confirmed in other studies.

Handgrip strength measured by a dynamometer connected to a smartphone: a new applied health technology solution for the self-assessment of rheumatoid arthritis disease activity.

OBJECTIVE: The aim was to analyse the accuracy of a hand dynamometer connected to a smartphone to assess RA disease activity through the measurement of handgrip strength (HGS). METHODS: Eighty-two RA patients participated in this prospective study. Three types of HGS were assessed: power (Po), pinch (Pi) and tripod (T). An interactive mobile application was developed to capture grip measures. A unilinear regression analysis between HGS and DAS28 was performed. A multivariate regression analysis to identify independent variables related to HGS was also conducted. RESULTS: Sixty-three patients (76.8%) were female. Mean age was 61.3 years. At baseline, a negative correlation between the three HGS measures and DAS28 score was found, as follows: Po, r = -0.65 (95% CI: -0.76, -0.51, P < 0.001); Pi, r= -0.42 (95% CI: -0.59, -0.23, P < 0.001); and T, r = -0.47 (95% CI: -0.63, -0.29, P < 0.001). In a longitudinal analysis of 32 patients, a negative correlation between ΔPo grip and ΔDAS28 was found (r = -0.76, 95% CI: -0.88, -0.56). Po grip was independently correlated with male sex (95% CI: 1.49, 4.14, P = 0.002), whereas variables inversely correlated with Po grip were disease duration (95% CI: -2.71, -1.34, P = 0.03), patient global assessment (95% CI: -2.41, -1.1, P < 0.001) and CRP level (95% CI: -3.56, -1.08, P < 0.001). CONCLUSION: HGS assessed by a hand dynamometer connected to a smartphone represents an innovative health technology solution that could prompt the self-assessment of RA disease activity in an outpatient setting.

Musculoskeletal symptoms in patients with cryopyrin-associated periodic syndromes: a large database study.

OBJECTIVE: To determine the type and frequency of musculoskeletal symptoms at onset and during followup of cryopyrin-associated periodic syndromes (CAPS). METHODS: We retrospectively recorded the articular and muscular symptoms of patients with CAPS followed up in French hospitals. Data were presented as frequencies or the median (range), and patient groups were compared using chi-square test, Fisher's exact test, and Mann-Whitney test. RESULTS: The study included 133 patients (33 children), 20 with familial cold autoinflammatory syndrome, 88 with Muckle-Wells syndrome, 22 with chronic infantile neurologic, cutaneous, articular syndrome, and 3 with unclassified CAPS. The median age was 35 years (range 0-78 years) at the time of the study, 1 year (range 0-41 years) at symptom onset, and 23 years (range 0-58 years) at diagnosis. The disease was sporadic in 17% of the patients. Cutaneous symptoms predominated at onset (77%), followed by articular symptoms (30%). The p.Thr348Met and p.Arg260Trp NLRP3 mutations were significantly associated with the presence and absence of articular symptoms at onset, respectively. During followup, 86% of the patients had musculoskeletal symptoms, 88% had arthralgia, and 58% had arthritis, but only 9% had joint destruction. Tendinopathies occurred in 21.5% of the patients, tender points in 16.5%, and myalgia in 33%. Only 3 patients had typical knee deformities. Radiographs were rarely obtained. Except for bone deformities, osteoarticular symptoms occurred at similar frequencies in the different CAPS phenotypes. CONCLUSION: Joint manifestations were frequent in all CAPS phenotypes. Bone deformities were rare. Musculoskeletal manifestations varied within given families but tended to worsen over time.

A severe Whipple disease with an immune reconstitution inflammatory syndrome: an additional case of thalidomide efficiency.

We report the case of a 38-year-old man who presented with severe diarrhea, weight loss of 10 kg, ankles paresthesia and severe motor weakness in the left fibular nerve territory after introduction of azathioprine and corticosteroid for proteinuria. Coloscopy and gastroscopy revealed a typical aspect of Whipple disease (WD), associated with both positive PAS staining and specific immunohistochemistry. T. whipplei PCR results were positive in blood, faeces, saliva and duodenal biopsy specimens. Diagnosis of WD with systemic manifestations was retained and doxycycline plus hydroxychloroquine therapy were started. This treatment improved joint pain, and skin and intestinal symptoms. One month later, our patient presented with fever and an important inflammatory syndrome (CRP 150 mg/dL and 16.8 10(9)/L leukocytes), while no infection was found despite a thorough review. We concluded it was an immune reconstitution inflammatory syndrome (IRIS). Manifestations persisted despite increasing corticosteroids and thalidomide (200 mg/day) was introduced with good efficacy on these symptoms. WD may be revealed by non-specific symptoms such as weight loss or arthralgia, but also by many other misleading signs. Our observation illustrates the highly polymorphic clinical presentation of WD, and the diagnostic difficulties that may arise. This is also a new report of thalidomide effectiveness in IRIS in WD.

Risk of malignancy including non-melanoma skin cancers with anti-tumor necrosis factor therapy in patients with rheumatoid arthritis: meta-analysis of registries and systematic review of long-term extension studies.

OBJECTIVES: To assess the risk of malignancy in patients with rheumatoid arthritis (RA) receiving tumour necrosis factor (TNF) antagonists through a meta-analysis of data from registry studies and systematic review of long-term extension (LTE) studies. METHODS: We systematically reviewed the literature up to January 2010 in the Embase and Medline databases, as well as abstracts from the 2008 and 2009 annual meetings of the EULAR and the ACR. The Mantel-Haenszel method was used to provide a common odds ratio (OR). Statistical heterogeneity was assessed by the chi-square Q test (χ²). Standardised incidence ratio (SIR) was extracted for post-marketing studies and registries. RESULTS: The literature search identified 634 articles and 110 abstracts, of which 12 and 5, respectively, were selected for analysis. We could perform a meta-analysis of data from 4 and 3 registries for risk of total malignancy and non-melanoma skin cancers (NMSC), respectively. The pooled OR for total malignancy and for NMSC was 0.81 [95% confidence interval (CI) 0.71-0.94] and 0.79 [0.62-1.02] in TNF antagonist group versus DMARD group, respectively. There was no significant heterogeneity. Among 4 LTE studies and 4 registries, no significant increase in the incidence of total malignancy was noted versus the general population. The only signal may be an increased risk of non-melanoma skin cancers. CONCLUSIONS: Our meta-analysis of data from registries and systematic review of LTE studies did not reveal an increased risk of total malignancy in RA patients receiving anti-TNF therapy.

Short-term risk of total malignancy and nonmelanoma skin cancers with certolizumab and golimumab in patients with rheumatoid arthritis: metaanalysis of randomized controlled trials.

OBJECTIVE: To assess the risk of total malignancy and nonmelanoma skin cancers (NMSC) in patients with rheumatoid arthritis (RA) receiving certolizumab and golimumab through a metaanalysis of data from randomized control trials (RCT). METHODS: We systematically reviewed the literature up to May 2011 in Medline databases, as well as abstracts from the 2009 and 2010 annual meetings of the European League Against Rheumatism and the American College of Rheumatology. Mantel-Haenszel method was used to determine a common odds ratio (OR). Statistical heterogeneity was assessed by chi-square Q test. We selected only RCT including more than 30 RA subjects randomly assigned to an anti-tumor necrosis factor (TNF) or a nonbiological disease-modifying antirheumatic drug (DMARD) control group. RESULTS: The literature search identified 793 articles; 6 (2 with certolizumab and 4 with golimumab) were selected for metaanalysis. A total of 2710 patients received at least 1 dose of certolizumab or golimumab. For anti-TNF-treated patients, 18 cancers (excluding NMSC) and 9 NMSC were observed versus 4 cases of total malignancy and 3 NMSC in control groups. Metaanalysis revealed a pooled OR of 1.06 (95% CI 0.39-2.85) for risk of total malignancy and 0.69 (95% CI 0.23-2.11) for risk of NMSC with certolizumab and golimumab versus DMARD. Heterogeneity was not significant. CONCLUSION: Metaanalysis of RCT of golimumab and certolizumab did not find an increased risk of total malignancy and NMSC. These results must be confirmed with longterm extension studies and registry studies, and careful monitoring remains mandatory.