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Background:Only few case reports and case series have analysed the efficacy of IL-1 inhibitors in the treatment of calcium pyrophosphate deposition disease (CPPD), reporting conflicting results.Objectives:The main aim of this systematic literature review (SLR) was to summarize the evidence in the use of biological therapies in CPPD.Methods:PRISMA-IPD guidelines were used for this review. Published articles reporting the use of TNFα and/or IL-1 inhibitors in the treatment of CPPD were reviewed. We performed a SLR using PubMed, Embase and Cochrane databases. The search resulted in 83 articles; 11 were further evaluated in the SLR.Results:Seventy-six patients were included: 2 received infliximab, whereas 74 anakinra. The main data of included studies are reported in table 1.Table 1.Studies evaluating biological therapies in patients with CPPD.AuthorsYear of publicationPopulation of interestNumber of CPPD patientsDiagnostic criteriaClinical presentationMcGonagle D. et al.2008CPPD1SFAChronicAnnoun N. et al.2009CPPD1SFAAcuteCouderc M. et al.2012CPPD3ImagingAcute and chronicDiamantopoulos A.P. et al.2012CPPD1SFAChronicMoltó A. et al.2012CPPD5SFAAcute and chronicOttaviani S. et al.2013CPPD16SFA and/or imagingAcuteVerhoeven F. et al.2013G and CPPD2NRAcute and chronicBruges-Armas J. et al.2014CPPD2NRChronicAouba A. et al.2015G, CPPD and HADD1ImagingAcuteDesmarais J. et al.2018G, CPPD11SFA and/or imagingAcuteThomas M. et al.2018CPPD32SFA and/or imagingAcuteLegend.G: gout,HADD: hydroxyapatite deposition disease,NR: not reported,SFA: synovial fluid analysisTable 2.Efficacy of anakinra in the treatment of CPPDAcute CPPD (n=67)Chronic CPPD (n=7)Clinical efficacy (%)54 (80.6)3 (42.9)Pre TJC6.3±2.43.8±2.4Post TJC1.2±0.61.3±1.5Mean reduction5.1±2.3*2.5±1.9+Pre SJC4.8±2.23.8±2.4Post SJC1.1±0.61.3±1.5Mean reduction3.7±2.2*2.5±1.9+Pre VAS pain (0-100 mm)68.5±9.5/Post VAS pain (0-100 mm)24.2±10.4/Mean reduction44.2±10.9*/Pre CRP (mg/l)40.9±50.950.0±66.5Post CRP (mg/l)22.2±8.63.2±2.5Mean reduction18.6±54.1*46.7±64.0+Legend. CRP: C-reactive protein,SJC: swollen joint count,TJC: tender joint count,VAS: visual analogue scale.+p values were not calculated because of a too small sample size. * p values were <0.01Sixty-seven (88.2%) patients presented with an acute CPPD (mean disease duration: 2.7±6.9 months; polyarticular involvement in 61.2%, oligoarticular in 31.3% and monoarticular in 7.5%), whereas 9 (11.8%) patients with a chronic CPPD (mean disease duration: 130.1±133.6 months; polyarticular involvement in 66.7% and oligoarticular in 33.3%).Anakinra was used in refractory disease (85.1%) or in patients with contraindications to standard treatments such as colchicine, oral glucocorticoids and/or non-steroidal anti-inflammatory drugs (23.0%). Clinical response to anakinra was reported in table 2.Duration of anakinra treatment prior to complete resolution of symptoms was associated with the clinical phenotype of chronic CPPD (Rpb: 0.67, p<0.01) and with disease duration (R: 0.49, p<0.01). In 47 out of 57 (82.5%) responders, complete resolution of symptoms was observed within 4 days after the first injection of anakinra. Adverse events were reported in 4.1% of the cases: local skin reaction at the injection site, skin rash on the back and bacterial pneumonia.Conclusion:This SLR provides evidence in favour of the use of anakinra as a therapeutic option in patients with CPPD, especially in acute refractory CPPD or when standard treatments are contraindicated.Disclosure of Interests: :Edoardo Cipolletta: None declared, Andrea Di Matteo Grant/research support from: the publication was conducted while Dr. Di Matteo was an ARTICULUM fellow, Anna Scanu: None declared, Martina Isidori: None declared, Jacopo Di Battista: None declared, Leonardo Punzi: None declared, Walter Grassi Speakers bureau: Prof. Grassi reports personal fees from AbbVie, personal fees from Celgene, personal fees from Grünenthal, personal fees from Pfizer, personal fees from Union Chimique Belge Pharma, outside the submitted work., Emilio Filippucci Speakers bureau: Dr. Filippucci reports personal fees from AbbVie, personal fees from Bristol-Myers Squibb, personal fees from Celgene, personal fees from Roche, personal fees from Union Chimique Belge Pharma, personal fees from Pfizer, outside the submitted work.

Objective To investigate whether baseline monosodium urate (MSU) burden estimated by ultrasound (US) predicts the achievement of the 2016 remission criteria for gout after 12 months. Methods In this 12-month prospective, observational and single-center study, patients with gout fulfilling all the domains of the 2016 preliminary remission criteria for gout at baseline and on urate-lowering therapy (ULT) for at least the preceding 6 months were consecutively enrolled. The US findings indicative of MSU deposits [aggregates, double contour (DC) sign, and/or tophi] were identified according to the Outcome Measure in Rheumatology US Working Group definitions. The US MSU burden was estimated by evaluating elbows, wrists, 2nd metacarpophalangeal joints, knees, ankles, and 1st metatarsophalangeal joints. Results Remission criteria were fulfilled in 21 (42.0%) out of 50 patients at 12 months. The baseline US MSU burden was significantly lower in patients who achieved remission than in those who did not fulfill the remission criteria at 12 months (1.9±1.8 vs 5.1±3.1, p<0.01). US scores and ongoing flare prophylaxis were the only significant predictors of remission with an odds ratio of 10.83 [(95%CI=1.14–102.59), p=0.04] for the absence of MSU deposits, 5.53 [(95%CI=1.34–22.76), p<0.01] for the absence of aggregates, 7.33 [(95%CI=1.71–31.44), p<0.01] for the absence of DC sign, 3.88 [(95%CI=1.08–13.92), p=0.04] for the absence of tophi, and 0.23 [(95%CI=0.07–0.75), p=0.02] for ongoing flare prophylaxis. Conclusion In gout, baseline US estimation of MSU burden is an independent predictor of the achievement of the remission criteria at 12 months.

Objectives To determine an ultrasound (US) scanning protocol with the best accuracy for the diagnosis of gout and CPPD in patients with acute mono/oligoarthritis of unknown origin. Methods Patients with acute mono/oligoarthritis, in whom a joint aspiration at the most clinically involved joint (target joint) was requested, were consecutively enrolled. US was performed in each patient before the arthrocentesis. The accuracy of different US findings and scanning protocols for the diagnosis of gout and CPPD was calculated. Results 161 subjects were included (32 gout patients, 30 CPPD patients and 99 disease-controls). US findings had a high specificity for gout (0.92-0.96) and CPPD (0.90-0.97), while the sensitivity ranged from 0.73 to 0.85 in gout (double contour sign and tophi, respectively) and from 0.60 to 0.90 in CPPD (hyaline and fibrocartilage deposits, respectively). The US assessment of two joints bilaterally (gout: knees, MTP1js, CPPD: knees, wrists) + the target joint had an excellent diagnostic sensitivity (gout:0.91, CPPD:0.93) and specificity (gout:0.91, CPPD:0.89). This targeted US scanning protocol yielded to higher diagnostic accuracy compared to the US evaluation of the target joint (gout, AUC:0.91 vs AUC:0.84, p = 0.03; CPPD, AUC:0.93, vs AUC:0.84, p = 0.04) unless the target joint was the knee or the MTP1j in gout, and the knee or the wrist in CPPD. Conclusions A targeted US scanning protocol of two joints bilaterally + the target joint (unless this was the knee, MTP1j or the wrist) showed an excellent accuracy (&gt;90%) for the diagnosis of crystal arthritis in patients with acute mono/oligoarthritis.