Production of IL-1β, TNF-α and IL-6 by PBMCs of 2 Schnitzler syndrome (SS-1 for patient 1 and SS-2 for patient2) patients and 6 healthy subjects (HSs) in different conditions of culture.

<p>(i) baseline: no stimulation condition of PBMCs; (ii) LPS stimulation (100 pg/ml); (iii) LPS stimulation (100 pg/ml) plus 500 ng/ml anakinra <i>in vitro.</i> Release of cytokine was evaluated in the supernatants collected at both 6 hours (middle gray histograms) and 16 hours (dark gray histograms) of culture conditions. Results are expressed as the mean of triplicate measures of cytokine concentration (± SD). In the SS patients, cytokine release was measured before and 1 month after <i>in vivo</i> anakinra treatment. In HSs, cytokine release is expressed as the mean of values (+/− SD) obtained in 6 independent evaluations.</p

Evolution of FVC during the follow up.

<p>Panel A represents the individual data of the 75 patients and the red line is the trajectory of FVC using the linear mixed model with random effect. There was no significant change of FVC over time. Panel B is the progression-free survival of FVC. Progression was defined as a decline of ≥10% of baseline FVC.</p

Evolution of DLCO during the follow up.

<p>Panel A represents the individual data of the 75 patients and the red line is the trajectory of DLCO using the linear mixed model with random effect. DLCO significantly decreased over time (-1.5±0.3%/year (p<0.0001). Panel B is the progression-free survival of DLCO. Progression was defined as a decline of ≥15% of baseline DLCO.</p

Trajectories of DLCO of patients with various clinical characteristics, using the linear mixed model with random effect.

<p>Panel A. Patients with presence or history of digital ulcers (DU) had a significantly higher baseline DLCO% but a faster decline of DLCO than patients without presence or history of digital ulcers (no DU) in multivariate analysis: -2.45±0.45 vs -1.01±0.33%/year (p = 0.01). Panel B. Patients with a right heart catheterization-proven precapillary pulmonary hypertension at baseline or during follow-up (PH) had a similar baseline DLCO% but a faster decline of DLCO than patients without a right heart catheterization-proven precapillary pulmonary hypertension at baseline or during follow-up (no PH) in multivariate analysis: -2.37±0.55 vs -1.19±0.31%/year (p = 0.049). Panel C. Patients with a limited ILD according to Goh <i>et al</i>. had a significantly higher baseline DLCO than patients with an extensive ILD but the slope of decrease in DLCO was similar in both groups (-1.69±0.33 vs -0.90±0.53%/year (p = 0.21). Panel D. Patients with a limited cutaneous SSc (lcSSc) had similar baseline DLCO and slope of decrease in DLCO than patients with diffuse SSc (dSSc) (p = 0.40 and p = 0.93, respectively).</p

Bivariate analysis of parameters associated with baseline value and slope of DLCO.

<p>Bivariate analysis of parameters associated with baseline value and slope of DLCO.</p

Efficacy of Rituximab in Refractory Inflammatory Myopathies Associated with Anti- Synthetase Auto-Antibodies: An Open-Label, Phase II Trial

<div><p>Objective</p><p>Anti-synthetase syndrome (anti-SS) is frequently associated with myositis and interstitial lung disease (ILD). We evaluated prospectively, in a multicenter, open-label, phase II study, the efficacy of rituximab on muscle and lung outcomes.</p><p>Methods</p><p>Patients were enrolled if they were refractory to conventional treatments (prednisone and at least 2 immunosuppressants). They received 1 g of rituximab at D0, D15, and M6. The primary endpoint was muscular improvement based on manual muscular testing (MMT10, Kendall score in 10 muscles) at M12. Secondary endpoints were normalization of creatine kinase (CK) level, ILD improvement based on forced vital capacity and/or diffuse capacity for carbon monoxide, and number and/or doses of associated immunosuppressants.</p><p>Results</p><p>Twelve patients were enrolled, and 10 completed the study. Only 2 patients presented an improvement of at least 4 points on at least two muscle groups (primary end-point). Overall, seven patients had an increase of at least 4 points on MMT10. CK level decreased from 399 IU/L (range, 48–11,718) to 74.5 IU/L (range, 40–47,857). Corticosteroid doses decreased from 52.5 mg/d (range, 10–70) to 9 mg/d (range, 7–65) and six patients had a decrease in the burden of their associated immunosuppressants. At baseline, all 10 patients presented with ILD. At M12, improvement of ILD was observed in 5 out of the 10 patients, stabilization in 4, and worsening in 1.</p><p>Conclusions</p><p>This pilot study of rituximab treatment in patients with refractory anti-SS provided data on evolution of muscular and pulmonary parameters. Rituximab should now be evaluated in a larger, controlled study for this homogenous group of patients.</p><p>Trial Registration</p><p>Clinicaltrials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT00774462" target="_blank">NCT00774462</a>.</p></div

High salivary-gland ultrasonography grade and high focus score predict the response to rituximab.

<p>SGUS, salivary gland ultrasonography; UWSF, unstimulated whole salivary flow. The response was assessed using the SSRI-30 (Sjögren’s Syndrome Response Index 30), defined as an at least 30% improvement from baseline to week 24 in at least two of the following five criteria: fatigue visual analogue scale [VAS], oral dryness VAS, ocular dryness VAS, unstimulated whole salivary flow, and erythrocyte sedimentation rate.</p

Interstitial lung disease evolution.

<p>Lung CT scans, before enrolment (M0) and 1 year later (M12), of the only patient with and nonspecific interstitial pneumonia improving after rituximab infusions.</p

Groups of patients.

<p>Groups of patients.</p

SF-36 scores measuring parameters of mobility.

<p>For each score (ranging from 0 to 100) the mean values (± SD) are represented at different time points: baseline (M0); months 6, 12 and 18 after rituximab infusion (M6, M12 and M18). The asterisk represents a significant increase (more than 10 points) compared with baseline.</p