Prolonged response after TPO-RA discontinuation in primary ITP: results of a prospective multicenter study.

Sustained response off treatment (SROT) after thrombopoietin receptor agonist (TPO-RA) discontinuation has been reported in immune thrombocytopenia (ITP). This prospective multicenter interventional study enrolled adults with persistent or chronic primary ITP and complete response (CR) on TPO-RAs. The primary end point was the proportion of patients achieving SROT (platelet count >30 × 109/L and no bleeding) at week 24 (W24) with no other ITP-specific medications. Secondary end points included the proportion of sustained CR off-treatment (SCROT, platelet count >100 × 109/L and no bleeding) and SROT at W52, bleeding events, and pattern of response to a new course of TPO-RAs. We included 48 patients with a median age of 58.5 years; 30 of 48 had chronic ITP at TPO-RA initiation. In the intention-to-treat analysis, 27 of 48 achieved SROT, 15 of 48 achieved SCROT at W24; 25 of 48 achieved SROT, and 14 of 48 achieved SCROT at W52. No severe bleeding episode occurred in patients who relapsed. Among patients rechallenged with TPO-RA, 11 of 12 achieved CR. We found no significant clinical predictors of SROT at W24. Single-cell RNA sequencing revealed enrichment of a tumor necrosis factor α signaling via NF-κB signature in CD8+ T cells of patients with no sustained response after TPO-RA discontinuation, which was further confirmed by a significant overexpression of CD69 on CD8+ T cells at baseline in these patients as compared with those achieving SCROT/SROT. Our results strongly support a strategy based on progressive tapering and discontinuation of TPO-RAs for patients with chronic ITP who achieved a stable CR on treatment. This trial was registered at www.clinicaltrials.gov as #NCT03119974.

Immune thrombocytopenia and pregnancy: an exposed/nonexposed cohort study.

The risk of immune thrombocytopenia (ITP) worsening during pregnancy and neonatal ITP (NITP) have never been prospectively studied. We included 180 pregnant and 168 nonpregnant women with ITP in a prospective, multicenter, observational cohort study. A total of 131 pregnant women with ITP were matched to 131 nonpregnant women with ITP by history of splenectomy, ITP status (no response, response, complete response), and duration. Groups were followed for 15 months. The primary outcome was the first occurrence of ITP worsening defined by a composite end point including bleeding events and/or severe thrombocytopenia (<30 × 109/L) and/or ITP treatment modification. We also studied the recurrence of ITP worsening and the incidence of NITP and risk factors. The first occurrence of ITP worsening did not differ between pregnant and nonpregnant women with ITP (53.4 per 100 person-years [95% confidence interval {CI}, 40.8-69.9] vs 37.1 [95% CI, 27.5-50.0]; hazard ratio {HR}, 1.35 [95% CI, 0.89-2.03], P = .16). Pregnant women with ITP were more likely to have recurrence of severe thrombocytopenia and treatment modification (HR, 2.71 [95% CI, 1.41-5.23], P = .003; HR, 2.01 [95% CI, 1.14-3.57], P = .017, respectively). However, recurrence of severe bleeding events was not different between groups (P = .4). Nineteen (14%) neonates showed NITP <50 × 109/L. By multivariable analysis, NITP was associated with a previous offspring with NITP and maternal platelet count <50 × 109/L within 3 months before delivery (adjusted odds ratio, 5.55 [95% CI, 1.72-17.89], P = .004 and 4.07 [95% CI, 1.41-11.73], P = .009). To conclude, women with ITP do not increase their risk of severe bleeding during pregnancy. NITP is associated with NITP history and the severity of maternal ITP during pregnancy. These results will be useful for counseling women with ITP.

Difficult-to-treat primary immune thrombocytopenia in adults: Prevalence and burden. Results from the CARMEN-France registry.

The aim of this study was to assess the prevalence and the burden of difficult-to-treat primary ITP (pITP), defined by the need for another ITP treatment after romiplostim and eltrombopag. Adult patients were selected in the prospective, real-world CARMEN-France registry up to December 2021. Out of 821 adult patients with pITP, 29 had difficult-to-treat ITP (3.5%; 95% confidence interval [CI]: 2.3%-4.8% in total; 7.6%; 95% CI: 4.9%-10.2% of patients needing ≥2nd line treatment). The 3-year cumulative incidence of bleeding, infection and thrombosis was 100%, 24.1% and 13.8% respectively. The median cumulative duration of hospital stays was 31 days (median follow-up: 30.3 months).

Comparison of daptomycin and glycopeptide efficacy and safety for the treatment of Gram-positive infections: a systematic review and meta-analysis.

BACKGROUND: The indications of daptomycin have been extended to off-label indications including prosthesis-related infection, and bone and joint infection (BJI). However, efficacy and safety have not been thoroughly demonstrated compared with the standard of care. This systematic review and meta-analysis aimed to compare the treatment effect of daptomycin and glycopeptides for complicated infections. MATERIALS AND METHODS: MEDLINE, Embase and Web of Science were searched for randomized controlled trials (RCTs) comparing daptomycin and standard of care for Gram-positive infections, published until 30 June 2021. The primary outcome was defined as all-cause mortality. Secondary outcomes were clinical and microbiological success. The main safety outcome was any severe adverse event (SAE) (grade  ≥3). RESULTS: Overall, eight RCTs were included in the meta-analysis, totalling 1095 patients. Six (75%) were in complicated skin and soft-structure infections, one (12.5%) in bacteraemia and one (12.5%) in a BJI setting. Six RCTs used vancomycin as a comparator and two used either vancomycin or teicoplanin. All-cause mortality and clinical cure were not different between groups. The microbiological cure rate was superior in patients who received daptomycin [risk ratio (RR) = 1.17 (95% CI: 1.01-1.35)]. The risk of SAEs [RR = 0.57 (95% CI: 0.36-0.90)] was lower in the daptomycin arm. CONCLUSIONS: While daptomycin is associated with a significantly lower risk of SAEs and a better microbiological eradication, substantial uncertainty remains about the best treatment strategy in the absence of good-quality evidence, especially in bacteraemia and endocarditis where further RCTs should be conducted.

Assessment of Clinical Worsening End Points as a Surrogate for Mortality in Pulmonary Arterial Hypertension: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Clinical worsening (CW) is a composite end point commonly used in pulmonary arterial hypertension (PAH) trials. We aimed to assess the trial-level surrogacy of CW for mortality in PAH trials, and whether the various CW components were similar in terms of frequency of occurrence, treatment-related relative risk (RR) reduction, and importance to patients. METHODS: We searched MEDLINE, Embase, and the Cochrane Library (January 1990 to December 2020) for trials evaluating the effects of PAH therapies on CW. The coefficient of determination between the RR for CW and mortality was assessed by regression analysis. The frequency of occurrence, RR reduction, and importance to patients of the CW components were assessed. RESULTS: We included 35 independent cohorts (9450 patients). PAH therapies significantly reduced CW events (RR, 0.64 [95% CI, 0.55-0.73]), including PAH-related hospitalizations (RR, 0.61 [95% CI, 0.47-0.79]), treatment escalation (RR, 0.57 [95% CI, 0.38-0.84]) and symptomatic progression (RR, 0.58 [95% CI, 0.48-0.69]), and modestly reduced all-cause mortality when incorporating deaths occurring after a primary CW-defining event (RR, 0.860 [95% CI, 0.742-0.997]). However, the effects of PAH-specific therapies on CW only modestly correlated with their effects on mortality (R2trial, 0.35 [95% CI, 0.10-0.59]; P<0.0001), and the gradient in the treatment effect across component end points was large in the majority of trials. The weighted proportions of CW-defining events were hospitalization (33.5%) and symptomatic progression (32.3%), whereas death (6.7%), treatment escalation (5.6%), and transplantation/atrioseptostomy (0.2%) were infrequent. CW events were driven by the occurrence of events of major (49%) and mild-to-moderate (37%) importance to patients, with 14% of the events valued as critical. CONCLUSIONS: PAH therapies significantly reduced CW events, but study-level CW is not a surrogate for mortality in PAH trials. Moreover, components of CW largely vary in frequency, response to therapy, and importance to patients and are thus not interchangeable. REGISTRATION: URL: https://www.crd.york.ac.uk/PROSPERO; Unique identifier: CRD42020178949.

Patients' perceptions on clinical trials outcomes in pulmonary arterial hypertension therapy.

The value placed by patients and their caregivers on the components of composite outcomes in pulmonary arterial hypertension (PAH) remains unknown. We surveyed the importance of these outcomes from a patients' and caregivers' perspective, with participants (n=335, including 257 patients with PAH) rating individual components defining clinical worsening in PAH trials as of critical, major, mild-to-moderate or minor importance. Most outcomes were considered of major or mild-to-moderate importance to patients. Death was the only outcome considered of critical importance. Perceptions of clinical outcomes varied between patients and caregivers. Integrating patients' perception in the elaboration of clinical trials is essential.

Heart and systemic sclerosis-findings from a national cohort study.

OBJECTIVES: Heart involvement is one of the leading causes of death in systemic sclerosis (SSc). The prevalence of SSc-related cardiac involvement is poorly known. Our objective was to investigate the prevalence and prognosis burden of different heart diseases in a nationwide cohort of patients with SSc. METHODS: We used data from a multicentric prospective study using the French SSc national database. Focusing on SSc-related cardiac involvement, we aimed to determine its incidence and risk factors. RESULTS: Over the 3528 patients with SSc 312 (10.9%) had SSc-related cardiac involvement at baseline. They tended to have a diffuse SSc subtype more frequently, more severe clinical features, and presented more cardiovascular risk factors. From the 1646 patients available for follow-up analysis, SSc-related cardiac involvement was associated with an increased risk of death. There was no significant difference in overall survival between SSc-related cardiac involvement, ischaemic heart disease or pulmonary arterial hypertension. Regarding survival analysis, 98 patients developed SSc-related cardiac involvement at five years (5-year event rate: 11.15%). Regarding reduced LVEF < 50% and left ventricular diastolic dysfunction, the 5-year event rate was 2.49% and 5.84% respectively. Pericarditis cumulative incidence at five years was 3%. Diffuse SSc subtype was a risk factor for SSc-related cardiac involvement and pericarditis. Female sex was associated with less left ventricular diastolic dysfunction incidence. CONCLUSIONS: Our results describe the incidence and prognostic burden of SSc-related cardiac involvement at a large scale, with gender and diffuse SSc subtype as risk factors. Further analyses should assess the potential impact of treatment on these various cardiac outcomes.

SGLT2 inhibitors in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials balancing their risks and benefits.

AIMS/HYPOTHESIS: Cardiovascular outcome trials (CVOTs) have demonstrated the benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i). However, serious adverse drug reactions have been reported. The risk/benefit ratio of SGLT2i remains unquantified. We aimed to provide an estimation of their risk/benefit ratio in individuals with type 2 diabetes. METHODS: We conducted a systematic review (MEDLINE, up to 14 September 2021) and meta-analysis. We included randomised CVOTs assessing SGLT2i in individuals with type 2 diabetes with or without other diseases. We used the Cochrane 'Risk of bias' assessment tool. The primary outcomes were overall mortality, major adverse cardiovascular events (MACE), hospitalisation for heart failure (HHF), end-stage renal disease (ESRD), amputation, diabetic ketoacidosis (DKA) and reported genital infections. For each outcome, we estimated the incidence rate ratio (IRR) with a 95% CI; we then computed the number of events expected spontaneously and with SGLT2i. RESULTS: A total of 46,969 participants from five double-blind, placebo-controlled international trials (weighted mean follow-up 3.5 years) were included. The prevalence of previous CVD ranged from 40.6% to 99.2%. The definition of reported genital infections ranged from 'genital mycotic infection' to 'genital infections that led to discontinuation of the trial regimen or were considered to be serious adverse events'. The number of included studies for each outcomes was five. The use of SGLT2i decreased the risk of all-cause death (IRR 0.86 [95% CI 0.78, 0.95]), MACE (IRR 0.91 [95% CI 0.86, 0.96]), HHF (IRR 0.69 [95% CI 0.62, 0.76]) and ESRD (IRR 0.67 [95% CI 0.53, 0.84]), and increased the risk of DKA (IRR 2.59 [95% CI 1.57, 4.27]) and genital infection (IRR 3.50 [95% CI 3.09, 3.95]) but not of amputation (IRR 1.23 [95% CI 1.00, 1.51]). For 1000 individuals treated over 3.5 years, SGLT2i are expected, on average, to decrease the number of deaths from 70 to 61, to prevent nine MACE, 11 HHF and two cases of ESRD, while inducing two DKA occurrences and 36 genital infections; 778 individuals are expected to avoid all the following outcomes: MACE, HHF, ESRD, amputation, DKA and genital infection. CONCLUSIONS/INTERPRETATION: Our study is limited to aggregate data. In a population of individuals with type 2 diabetes and a high CVD risk, the cardiovascular and renal benefits of SGLT2i remain substantial despite the risk of DKA and even the hypothetical risk of amputation. TRIAL REGISTRATION: OSF Registries: https://doi.org/10.17605/OSF.IO/J3R7Y FUNDING: This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

Immune thrombocytopenia with clinical significance in systemic lupus erythematosus: a retrospective cohort study of 90 patients.

OBJECTIVES: To describe the characteristics, treatment and outcome of patients with immune thrombocytopenia with clinical significance (ITPCS) associated with SLE. METHODS: This retrospective multicentre study included SLE patients who experienced ≥1 ITPCS (defined as ITP with attributable bleeding disorders and/or a platelet count <30×109/l). Other causes of secondary thrombocytopenia were excluded. Major bleeding event (MBG) was defined as Khellaf score >8 and/or WHO score >2. RESULTS: A total of 90 patients were included, the median (range) follow-up duration was 80 (6-446) months. ITP was diagnosed before SLE in 25 patients. They presented a high rate of autoimmune haemolytic anaemia (15%), antiphospholipid antibody (62%) and antiphospholipid syndrome (19%). The 25 (28%) patients who experienced MBG had significantly more bleedings at ITP diagnosis and higher bleeding scores, and serositis and thrombosis during follow-up. They required significantly more treatment lines, transfusions and hospitalizations. The 11 (12%) patients who experienced no bleeding event presented a significantly more restricted SLE phenotype (cutaneous and/or articular). Patients received a mean (range) of 4.2 (1-11) treatment lines. Corticosteroids and HCQ allowed ITPCS overall response in one-third of patients. The median relapse-free survival of rituximab (n = 34), AZA (n = 19), MMF (n = 8), thrombopoietin-receptor agonists (n = 16) and splenectomy (n = 19) were 53, 31.5, 61, 24.5 and 78 months, respectively. Four patients experienced thrombotic events after splenectomy and one occurred under thrombopoietin-receptor agonist treatment. CONCLUSION: SLE-ITCS patients displayed a high rate of haematological abnormalities and MBG patients exhibited higher morbidity. Management of thrombocytopenia was highly heterogeneous and many options seem viable.

Splenectomy for primary immune thrombocytopenia revisited in the era of thrombopoietin receptor agonists: New insights for an old treatment.

Although splenectomy is still considered the most effective curative treatment for immune thrombocytopenia (ITP), its use has significantly declined in the last decade, especially since the approval of thrombopoietin receptor agonists (TPO-RAs). The main objective of the study was to determine whether splenectomy was still as effective nowadays, particularly for patients with failure to respond to TPO-RAs. Our secondary objective was to assess, among patients who relapsed after splenectomy, the pattern of response to treatments used before splenectomy. This multicenter retrospective study involved adults who underwent splenectomy for ITP in France from 2011 to 2020. Response status was defined according to international criteria. We included 185 patients, 100 (54.1%) and 135 (73.0%) patients had received TPO-RAs and/or rituximab before the splenectomy. The median follow-up after splenectomy was 39.2 months [16.5-63.0]. Overall, 144 (77.8%) patients had an initial response and 23 (12.4%) experienced relapse during follow-up, for an overall sustained response of 65.4%, similar to that observed in the pre-TPO-RA era. Among patients who received at least one TPO-RA or rituximab before splenectomy, 92/151 (60.9%) had a sustained response. Six of 13 (46%) patients with previous lack of response to both TPO-RAs and rituximab had a sustained response to splenectomy. Among patients with relapse after splenectomy, 13/21 (61.2%) patients responded to one TPO-RAs that failed before splenectomy. In conclusion, splenectomy is still a relevant option for treating adult primary ITP not responding to TPO-RAs and rituximab. Patients with lack of response or with relapse after splenectomy should be re-challenged with TPO-RAs.

Arterial and venous thromboembolism in COVID-19: a study-level meta-analysis.

BACKGROUND: The prevalence of venous thromboembolic event (VTE) and arterial thromboembolic event (ATE) thromboembolic events in patients with COVID-19 remains largely unknown. METHODS: In this meta-analysis, we systematically searched for observational studies describing the prevalence of VTE and ATE in COVID-19 up to 30 September 2020. RESULTS: We analysed findings from 102 studies (64 503 patients). The frequency of COVID-19-related VTE was 14.7% (95% CI 12.1% to 17.6%, I2=94%; 56 studies; 16 507 patients). The overall prevalence rates of pulmonary embolism (PE) and leg deep vein thrombosis were 7.8% (95% CI 6.2% to 9.4%, I2=94%; 66 studies; 23 117 patients) and 11.2% (95% CI 8.4% to 14.3%, I2=95%; 48 studies; 13 824 patients), respectively. Few were isolated subsegmental PE. The VTE prevalence was significantly higher in intensive care unit (ICU) (23.2%, 95% CI 17.5% to 29.6%, I2=92%, vs 9.0%, 95% CI 6.9% to 11.4%, I2=95%; pinteraction<0.0001) and in series systematically screening patients compared with series testing symptomatic patients (25.2% vs 12.7%, pinteraction=0.04). The frequency rates of overall ATE, acute coronary syndrome, stroke and other ATE were 3.9% (95% CI 2.0% to to 3.0%, I2=96%; 16 studies; 7939 patients), 1.6% (95% CI 1.0% to 2.2%, I2=93%; 27 studies; 40 597 patients) and 0.9% (95% CI 0.5% to 1.5%, I2=84%; 17 studies; 20 139 patients), respectively. Metaregression and subgroup analyses failed to explain heterogeneity of overall ATE. High heterogeneity limited the value of estimates. CONCLUSIONS: Patients admitted in the ICU for severe COVID-19 had a high risk of VTE. Conversely, further studies are needed to determine the specific effects of COVID-19 on the risk of ATE or VTE in less severe forms of the disease.

Rectal endometriosis: predictive MRI signs for segmental bowel resection.

OBJECTIVE: To retrospectively determine the accuracy of MRI rectal and pararectal signs in predicting the necessity for segmental resection in the case of lesions located in the rectum. METHODS: MR images of consecutive patients treated for rectal endometriosis over a 5-year period were reviewed in consensus by two blinded readers. A systematic analysis of 7 rectal (lesion length, transverse axis, thickness and circumference, and presence of a convex base, submucosal oedema and hyperintense cystic areas) and 4 pararectal (posterior vaginal fornix, parametrial, ureteral and sacro-recto-genital septum involvements) signs was performed for each lesion. MRI results were compared to the surgical procedure performed (shaving versus segmental resection). RESULTS: Among 61 patients studied, 32 received a segmental resection and 29, a shaving. Receiver operating characteristic curve analysis allowed determining cut-off values for length (≥ 32 mm), transverse axis (≥ 22 mm), thickness (≥ 14 mm) and circumference (≥ 3/8 radii). The 7 rectal signs, and only the sacro-recto-genital septum pararectal sign, were significantly associated with segmental resection in univariate analysis, nodular thickness ≥ 14 mm and circumference ≥ 3/8 radii being the most predictive signs (odds ratio 94.5 and 60.4, respectively). These 2 signs remained positively associated with segmental resection in multivariate analysis and, when combined, were predictive of segmental resection with an accuracy of 90.2%. CONCLUSION: Assessing MRI rectal and pararectal signs may accurately predict the need for segmental resection versus a more conservative approach such as shaving for rectal lesion management. KEY POINTS: • MRI analysis of rectal endometriosis, taking into account rectal and pararectal signs, may assist surgeons in the decision-making process, in counselling patients regarding the surgical procedure and in adequately allocating resources. • Among rectal signs, nodular thickness ≥ 14 mm and a circumference ≥ 38% were the most predictive signs of segmental resection. • Among pararectal signs, only the sacro-recto-genital septum involvement was significantly associated with segmental resection.

The benefit-risk balance for biological agents in juvenile idiopathic arthritis: a meta-analysis of randomized clinical trials.

OBJECTIVE: To assess the net benefit of biological agents (BA) used in JIA. METHODS: We systematically searched databases up to March 2019 for randomized controlled trials (RCT) performed in JIA disease. Separate random-effects meta-analyses were conducted for efficacy (ACR paediatric score 30%, ACRpedi30) and serious adverse events for safety. In order to standardize the baseline risk, we performed a meta-analysis of baseline risk in the control group (for both efficacy and safety meta-analysis). The net benefit was determined as the risk difference of efficacy subtracted by the risk difference of safety. RESULTS: We included 19 trials: 11 parallel RCTs (754 patients) and 8 withdrawal RCTs (704 patients). The net benefit ranged from 2.4% (adalimumab) to 17.6% (etanercept), and from 2.4% (etanercept) to 36.7%, (abatacept) in parallel and withdrawal trials assessing non-systemic JIA, respectively. In the systemic JIA category, the net benefit ranged from 22.8% (rilonacept) to 70.3% (canakinumab), and from 32.3% (canakinumab) to 58.2% (tocilizumab) in parallel and withdrawal trials, respectively. CONCLUSION: The results suggest that a greater number of patients experienced therapeutic success without serious adverse events in the systemic onset JIA category compared with the BAs for non-systemic JIA categories. Baseline risk, design of trial and JIA categories impact the measure of net benefit of BAs in JIA patients.

Lung Diseases in Inflammatory Myopathies.

Lung involvement is the leading cause of mortality in inflammatory myopathy. A careful assessment of clinical and serologic manifestations especially myositis-associated autoantibodies allows precise classification of the different phenotypes of inflammatory myopathy and stratification of the risk of lung involvement. About three out of four patients with inflammatory myopathy develop interstitial lung disease (ILD), which represents the main cause of morbidity and mortality. In patients with a confirmed diagnosis of inflammatory myopathy, the approach to the diagnosis of ILD includes assessment of clinical and functional severity, evaluation of the high-resolution computed tomography pattern of disease, which often suggests nonspecific interstitial pneumonia or organizing pneumonia. Bronchoalveolar lavage to rule out infection is often performed; however, video-assisted thoracoscopic lung biopsy is now generally discouraged, unless malignancy is suspected. The so-called antisynthetase syndrome characterized by the combination of mechanics' hands, Raynaud' phenomenon, myositis often mild or absent, and presence of one of the anti-tRNA synthetase antibodies is associated with a 70% risk of ILD, especially in subjects with antibodies other than anti-Jo1 antibodies (i.e., anti-PL7 or -PL12 antibodies). Treatment depends on both severity and progression of ILD, often including a combination of corticosteroids and immunosuppressive therapy. Rituximab-based regimen has showed promising results in retrospective studies for the management of refractory or rapidly progressive forms of ILD. Clinical trials are ongoing to evaluate the actual efficacy of this strategy on mortality related to lung disease. Secondary pulmonary complications of inflammatory myopathy include opportunistic infections, aspiration pneumonia, pneumomediastinum, ventilatory failure due to diaphragmatic muscular weakness, drug-induced pneumonitis, and rarely pulmonary hypertension.

Risk of thrombosis with anti-phospholipid syndrome in systemic lupus erythematosus treated with thrombopoietin-receptor agonists.

OBJECTIVES: The use of thrombopoietin-receptor agonists (TPO-RAs) has increased as a second-line therapy in ITP, but the efficacy and safety of such drugs has not been evaluated in SLE-associated ITP. METHODS: This was a multicentre retrospective cohort study from 2009 to 2016. Participating centres (n = 11) were secondary- or tertiary-care hospitals belonging to the French national network for adult ITP. RESULTS: We included 18 patients with SLE-ITP treated with TPO-RAs; 10 (55%) had aPL, 5 (27%) showing definite APS. Except for one patient, all (94%) achieved response with TPO-RAs overall. After a median follow-up of 14.7 months with TPO-RAs, four arterial thrombosis events (including one catastrophic APS) occurred in four patients. Two venous thrombosis events occurred in a patient without APS or aPLs. CONCLUSION: Our results suggest that aPLs should be systematically screened before TPO-RA initiation in patients with SLE. With aPL positivity, alternative therapy should be discussed (if possible), especially in patients with definite APS or suboptimal adherence to anti-coagulation therapy.

Anti-C1q autoantibodies as markers of renal involvement in childhood-onset systemic lupus erythematosus.

BACKGROUND: Childhood-onset systemic lupus erythematosus (cSLE) is rare, and considered more severe than its adult-onset counterpart. Lupus nephritis (LN) occurs more frequently in children, accounting for higher long-term morbidity and mortality compared with adults. Thus, reliable biological markers are needed to predict disease course. This study aimed to investigate the capacity of anti-C1q autoantibodies (Abs) to predict renal flare and global disease activity in cSLE patients, and association with disease activity and kidney involvement. METHODS: Twenty-eight patients with cSLE including 19 patients (68%) with a history of LN were included retrospectively. Anti-C1q Abs were analysed by ELISA at renal flare-up or in the quiescent phase of disease and compared with Farr dsDNA assay. RESULTS: Thirty-one flares occurred during follow-up: anti-C1q Abs were positive in 26 (84%), strongly associated with active disease status (p < 0.0001), and correlated with global disease activity score (p < 0.0001) and anti-dsDNA Abs presence (p < 0.0001). The specificity of anti-C1q Abs was higher than anti-dsDNA (73% vs 19%) in discriminating LN patients, whereas the receiver operating characteristic curves were not statistically different (0.83 ± 0.06 vs 0.78 ± 0.08 respectively), similar to C3 dosage. The presence of anti-C1q Abs at diagnosis was not predictive for global or renal flare. Introduction of a modified SLEDAI score excluding dsDNA Abs, demonstrated a stronger correlation of anti-C1q Abs titres with SLEDAI score in comparison with the Farr test. CONCLUSION: Anti-C1q Abs seem very specific to flares, including LN in children, and their role in daily practice compared with the Farr dsDNA assay needs to be defined.