Thu0419 biologics in the Treatment of Calcium Pyrophosphate Deposition Disease. A Systematic Literature Review

Abstract

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.

High prevalence of chondrocalcinosis and frequent comorbidity with calcium pyrophosphate deposition disease in patients with seronegative rheumatoid arthritis

“…The differences in treatment found in our study are consistent with current strategies in the management of CPPD but there is no evidence for the treatment of this ‘common but neglected form of arthritis43 ’ by commonly administered agents such as NSAIDs, corticosteroids and colchicine. Nevertheless, there is limited evidence for an effect of the anti-interleukin (IL)-1 bDMARD anakinra 44. Although the effect of an anti-IL-1 agent may argue in favour of an autoinflammatory disease, it is stressed that anakinra is also approved for the treatment of RA 45…”

The role of Interleukin-1 receptor antagonist as a treatment option in calcium pyrophosphate crystal deposition disease

“…1 patient had no response Local skin reaction at the injection site in 1 patient Efficacy of anakinra in calcium pyrophosphate crystal-induced arthritis: a report of 16 cases and review of the literature [ 54 ] Observational retrospective study 16 75% had 100 mg/day sc for 3 days in 12 patients 25% had 100 mg/day sc for 7 days-6 months Among 12 patients treated for 3 days 67% had good response, 25% had partial response, 8% had no response Among the other 4 patients, 2 had good response, 1 had partial response and 1 had no response No adverse events were reported Use of anakinra in hospitalized patients with crystal-associated arthritis [ 60 ] Observational retrospective study 100 patients with gout and CPPD disease with 115 episodes of arthritis 80.8% of episodes were treated with 100 mg/day sc for 1–3 days 19.2% of episodes were treated with 100 mg/day sc for more than 3 days 73% of episodes had complete or partial response within 4 days after the first dose 57,3% of episodes had complete or partial response within 1 day after the first dose 6% of episodes had partial response… 5.2% of episodes had no response……… ……… No adverse events were reported. In 29 patients with concomitant infection there were no signs of worsening Biologics in the treatment of calcium pyrophosphate deposition disease: systematic literature review [ 61 ] Systematic literature review 76 74 patients (97.7%) received anakinra at dose of 100 mg/day Among these patients, 76.1% was treated with 1–3 days, 23.9% was treated for 5–9 days 80.6% had clinical response among those patients with acute CPP crystals arthritis 42.9% had clinical response among those patients with chronic CPP crystals arthritis Adverse events were reported in 4.1% of patients. Mainly skin reaction at site injection and respiratory infection …”

“…This suggests that longer treatment may be necessary in patients with a longer duration of the disease or with chronic CPPD disease. However, the most important effect was observed on acute CPP crystal arthritis with a significant reduction of TJC, SJC, VAS pain and CRP level [ 61 ].…”

“…As shown by Cipolletta et al clinical response to anakinra was more evident in acute CPP crystal arthritis, with a response rate of 80.6%, than in chronic CPP crystal arthritis (response rate of 42.9%), although the last case probably depends on the small sample size, which doesn’t allow to draw any definitive conclusion [ 61 ]. However, all the studies reported show that in chronic CPP crystal arthritis, anakinra could inhibit onset of a new flare of disease.…”

Acute Calcium Pyrophosphate Crystal Arthritis of the Wrist Elicited by Anti-COVID-19 Vaccination After Carpal Tunnel Release

“…Commonly used treatments are NSAIDs, colchicine, and systematic corticosteroids, depending on patient’s comorbidities and response to previous treatments. Biologic drugs like IL-1 receptor antagonist anakinra appear promising in the management of CPPD, especially in acute refractory CPPD or when standard treatments are contraindicated [ 10 , 12 ].…”