The Efficacy of Denosumab in Patients With Rheumatoid Arthritis: A Systematic Review and Pooled Analysis of Randomized or Matched Data

ObjectiveThe purpose of this study was to evaluate the efficacy of denosumab treatment in patients with rheumatoid arthritis (RA).MethodsThe Medline, Embase and Cochrane Library databases were searched for relevant clinical studies. Studies that assessed the efficacy of denosumab in patients with RA were identified. The primary endpoints were the percent changes in bone mineral density (BMD), and the changes in modified total Sharp score (mTSS), modified Sharp erosion score and joint space narrowing (JSN) score. Pooled analyses were calculated using random-effect models.ResultsAfter searching the literature and performing further detailed assessments, 10 studies with a total of 1758 patients were included in the quantitative analysis. Pooled analyses showed that denosumab treatment significantly increased the percent changes in lumbar spine BMD [mean difference (MD): 5.12, confidence intervals (CI): 4.15 to 6.09], total hip BMD (MD: 2.72, 95% CI: 1.80 to 3.64) and femoral neck BMD (MD: 2.20, 95% CI: 0.94 to 3.46) compared with controls. Moreover, denosumab treatment significantly decreased the changes in mTSS (MD: -0.63, 95% CI: -0.86 to -0.41) and modified Sharp erosion score (MD: -0.62, 95% CI: -0.88 to -0.35). Subgroup analysis indicated that denosumab was superior to bisphosphonates for the improvement of BMD and the mitigation of joint destruction.ConclusionDenosumab treatment was associated with increased BMD and alleviated progression of joint destruction in RA patients, even when compared with bisphosphonates.

Prevalensi Karies dan Erosi pada Narapidana Pengguna Narkotika Jenis Sabu-Sabu di Lembaga Pemasyarakatan Klas II-A Kabupaten Jember

The problem of methamphetamine abuse in Indonesia is still very concerning even though the prohibition on consuming narcotics outside of medical indications has been regulated in law. Methamphetamine users are at high risk for tooth decay, tooth decay that often occurs in methamphetamine users is caries and erosion. This is because the abuse of methamphetamine can affect the oral hygiene and saliva quality of the users. Given the high risk of methamphetamine users being exposed to caries and erosion, researchers need to conduct research that aims to determine the prevalence of caries and erosion, as well as describe the characteristics of inmates who use shabushabu narcotics in the Class II-A Penitentiary Office Jember. There are 58 respondents in this study. Caries measurement was carried out using the DMF-T index, erosion measurement was carried out using the Basic Erosive Wear Examination, while the characteristics of the respondents were obtained through a questionnaire sheet. The result is that the prevalence of caries in methamphetamine users is 89.66% with a mean DMF-T score of 7.21 and the prevalence of erosion is 72.41% with a mean erosion score of 5.29. It can be concluded that most users of methamphetamine have caries and erosion problems in their teeth.

The Role of Autoimmunity on the Relation Between Erosions and Bone Mineral Density in Rheumatoid Arthritis: A Clinical Research

IntroductionBoth erosions and osteoporosis are present in rheumatoid arthritis and are related to RANK-L pathway activation. The aim of the study was to evaluate the relationship between erosion and bone mineral density (BMD) in RA and whether it can be driven by autoimmunity.Patients and methodsPatients followed in the Department of Rheumatology between January 2008 and May 2019 satisfied the 1987 ACR or 2010 ACR-EULAR criteria. Erosions were evaluated by the modified Sharp/van der Heidje erosion score (SHSe) on radiographs and bone mineral density (BMD) in g/cm2 and by the T-score at the hip on DXA. The presence and titers of ACPA as well as rheumatoid factor (RF) and anti-nuclear antibodies (ANAs) were recorded at intervals of less than 2 years for both DXA and radiography.ResultsA total of 149 patients met the inclusion criteria. A total of 61.1% were ACPA positive, 79.9% were erosive and 10.7% had a hip T-score ≤-2.5. ACPA status but not titers was associated with a higher erosion score (63.0 (53.2) for ACPA + vs. 45.5 (44.1) for ACPA – (p= 0.04)). ACPA titers were associated with lower BMD at the hip (value -0.216; p=0.01) but not with T-score. A higher erosion score was associated with a lower BMD (R2: 0,049 and value: -0.222; p=0.009) and T-score (R2: 0,158 and value -0.397; p<0.0001) at the hip. In linear regression, erosion and systemic bone loss were still associated with but not driven by ACPA status or titer. RF and ANA did not demonstrate any role in this association.ConclusionWe showed that the relationship between erosion and bone mineral density associated with RA does not seem to be driven by ACPA or other autoimmunity parameters. However, the presence of ACPA or erosion should lead to osteoporosis assessment.

SAT0031 CORRELATION BETWEEN IRREVERSIBLE PHYSICAL DISABILITY AND JOINT DAMAGE IN RHEUMATOID ARTHRITIS

Background:In rheumatoid arthritis (RA), irreversible physical disability appears to be more clearly associated with cartilage damage rather than with bone erosions (BE) using conventional radiography (CR) imaging.Objectives:To investigate the correlation between the ultrasound (US) and CR findings indicative of joint damage and irreversible physical disability in patients with RA in sustained clinical remission.Methods:Patients in sustained clinical remission according to the Simplified Disease Activity Index (SDAI)≤3.3 for at least 6 months were enrolled. The following data were regireted: age, disease duration, anti-cyclic citrullinated peptide (ACPA) antibody and rheumatoid factor (RF) status, Health Assessment Questionnaire (HAQ), CR of hands and feet [evaluated using the Simple Erosion Narrowing Score (SENS) method]. A standardized US examination was carried out to investigate the presence of BE (lateral side of II metacarpophalangeal, V metacarpophalangeal and V metatarsophalangeal joints and ulnar styloid) and of cartilage damage (II to V metacarpal heads), bilaterally. BE and cartilage damage were assessed according to OMERACT definitions. A semiquantitative scoring system for both BE (1) and cartilage damage (2) was adopted.Results:Ninety patients were consecutively enrolled. Average time for US evaluation was 10±2 minutes. Both SENS-JSN and US score of cartilage damage (US-CD) were significantly associated with irreversible disability (R=0.39, p<0.01 and R=0.46, p<0.01). US and CR showed a moderate agreement in the evaluation of cartilage damage (kappa=0.52, 95% confidence interval: 0.44-0.61).Figure 1.shows the association between disability and structural damage (A: US-CD, B: US-BE, C: SENS-JSN and D: SENS-BE). After adjusting for confounding factors (age, disease duration, ACPA and RF status, SENS-BE and US-BE) cartilage damage was the only significant predictor of irreversible disability both using CR (R2=0.31, adjusted R2=0.26, standardized β=0.36, p<0.01) and US (R2=0.31, adjusted R2=0.26, standardized β=0.34, p<0.01).Conclusion:This study supports the hypothesis that cartilage damage is more relevant than BE in determining irreversible disability in RA. Our data provide further evidence in favor of the external validity of US in the assessment of cartilage damage.References:[1] Ohrndorf S, Messerschmidt J, Reiche BE, et al. Evaluation of a new erosion score by musculoskeletal ultrasound in patients with rheumatoid arthritis: is US ready for a new erosion score? Clin Rheumatol. 2014;33:1255-62.[2] Mandl P, Studenic P, Filippucci E, et al. Development of semiquantitative ultrasound scoring system to assess cartilage in rheumatoid arthritis. Rheumatology (Oxford). 2019;58:1802-11.Disclosure of Interests:Edoardo Cipolletta: None declared, Antonella Incorvaia: None declared, Riccardo Mashadi Mirza: None declared, Andrea Di Matteo Grant/research support from: the publication was conducted while Dr. Di Matteo was an ARTICULUM fellow, Marika Tardella: 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.

SAT0548 DEVELOPMENT AND VALIDATION OF THREE PRELIMINARY MRI SACROILIAC JOINT COMPOSITE STRUCTURAL DAMAGE SCORES IN A 5-YEAR LONGITUDINAL STUDY OF PATIENTS WITH AXIAL SPONDYLOARTHRITIS

Background:In axial spondyloarthritis (axSpA), MRI reliably detects structural lesions in the sacroiliac joints (SIJs). The SPARCC SIJ Structural Score (SSS)(1) is a reliable and validated method to assess the individual structural lesions of the SIJs, i.e. fat lesion, erosion, backfill (fat metaplasia in an erosion cavity) and ankylosis. Several MRI studies have indicated that bone destruction, i.e. erosion, is often followed by formation of new bone in the erosion cavity (backfill), ultimately leading to ankylosis(2).Objectives:The aim was to combine SPARCC SSS for erosion, backfill and ankylosis into a composite score for SIJ structural damage and to test this score in a 5-year follow up study.Methods:Thirty-three patients fulfilling ASAS criteria for axSpA were followed for 5 years after initiation of TNF inhibitor in the BIOSPA study(3). T1-weighted and STIR MRI sequences of the SIJs acquired at week 0, 46 and year 2, 3, 4, 5 were evaluated with SPARCC SSS. In each of 5 slices of each SIJ, erosion is scored 0-1 per joint quadrant (score range 0-40), backfill 0-1 per joint half (score range 0-20) and ankylosis 0-1 per joint half (score range 0-20). Based on the scores for erosion, backfill and ankylosis 3 versions of a preliminary Composite axSpA MRI SIJ Structural Damage Score (CSDS) were calculated:CSDS–A: (erosion score x0.5) + backfill score + ankylosis scoreCSDS–B: (erosion score x1) + (backfill score x4) + (ankylosis score x6)CSDS–C: (erosion score x1) < (backfill score x4) < (ankylosis score x6)The “<” indicates a hierarchical order, meaning that erosion was not scored if backfill was present in the same joint half and erosion and backfill were not scored if ankylosis was present in the joint half.Results:Patients were divided into two groups: patients with almost complete bilateral ankylosis (baseline SPARCC SSS Ankylosis ≥18, n=10) and patients with no/minor ankylosis (baseline SPARCC SSS Ankylosis ≤7, n=23). At baseline patients with no/minor ankylosis were younger, had shorter symptom duration, lower BASMI, higher SPARCC SIJ Inflammation, lower SSS Fat, Erosion, Backfill and Ankylosis, as compared with patients with almost complete ankylosis.At baseline, CSDS-A, -B and -C correlated positively with SPARCC SSS Fat and Ankylosis and modified New York criteria grading, and negatively with BASDAI and SPARCC inflammation. Change in CSDS-B and -C over 5 years correlated positively with change in SSS Fat and Ankylosis and negatively with change in SPARCC Inflammation. There was no change in the group with almost complete ankylosis.The annual progression for CSDS-B and -C was statistically significantly larger in year 1 compared with year 4 (p=0.01) and numerically larger compared with year 2 (p=0.075), 3 (p=0.382) and 5 (p=0.073). Figure 1 shows the annual change in patients with no/minor ankylosis.Conclusion:Three preliminary Composite Structural Damage Scores for MRI assessment of the SIJs in patients with axSpA, which allows scoring of MRI progression of erosion through backfill to ankylosis, were introduced. Progression was most pronounced the first year after TNF inhibitor initiation. This novel approach may be useful for monitoring structural progression in axSpA. We suggest that these methods are further tested for responsiveness and ability to differentiate between different therapies in randomized controlled trials.References:[1]Maksymowych WP et al. J Rheum 2015;42:79-86.[2]Maksymowych WP et al. Art Rheum 2014;66:2958-67.[3]Pedersen SJ et al. Scand J Rheum 2019;48:185-197.Disclosure of Interests:Marie Wetterslev: None declared, Mikkel Ǿstergaard Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Merck, and Novartis, Consultant of: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB, Inge Juul Sørensen: None declared, Ulrich Weber: None declared, Anne Gitte Loft Grant/research support from: Novartis, Consultant of: AbbVie, MSD, Novartis, Pfizer and UCB, Speakers bureau: AbbVie, MSD, Novartis, Pfizer and UCB, Gina Kollerup Speakers bureau: Eli Lilly, Lars Juul: None declared, Gorm Thamsborg: None declared, Ole Madsen: None declared, Jakob Møllenbach Møller: None declared, Susanne Juhl Pedersen Grant/research support from: Novartis

SAT0474 WHAT DETERMINES THE EFFECT OF THERAPY WITH DENOSUMAB ON BONE IN WOMEN WITH RHEUMATOID ARTHRITIS AND OSTEOPOROSIS

Background:RANK-ligand is essential for osteoclast development, activation, and survival and it is a key mediator of increased osteoclast activity in rheumatoid arthritis (RA). Denosumab is a monoclonal antibody that binds RANK-ligand.Objectives:The aim of this study was to evaluate the effects of denosumab on bone mineral density (BMD) and to define a contribution of factors: anamnesis, clinical/laboratory markers, glucocorticoids (GC) intake, etc. on the response to therapy with denosumab in women with RA and osteoporosis (OP).Methods:66 postmenopausal women (mean age 59,6±7,4) with RA (mean duration 17,7±10,4 years) and OP received s/c denosumab 60 mg every 6 months pro 12 months. RF-positive were 72%, ACCP – 74% of patients. 34 (49%) patients continued GC. At baseline and after 12 months it was carried out the dual energy x-ray absorptiometry at 3 sites: lumbar spine (L1-L4), hip neck (HN) and distal forearm (DF) and x-ray of hands and feet (Sharp/van der Heijde (SVH) score). The Statistica 6.0 was used.Results:After therapy it was noted the increase (р < 0,05) of BMD in L1-L4 and HN, a tendency to increase (р =0,0529) in DF. Mean BMD (L1-L4) before\after the treatment was 0,821 ± 0,104 g/cm2vs 0,864 ± 0,110 g/cm2, at HN was 0,625 ± 0,089 g/сm2vs 0,639 ± 0,088 g/сm2, at DF was 0,498 ± 0,090 g/сm2vs 0,503 ± 0,089 g/сm2. The mean change of BMD (%) after 12 months at L1-L4 was +4,6%, at HN +2,8%, at DF +0,7%. Positive response (increase or stabilization of BMD) was noted in 89% patients at L1-L4, 67% - at HN and 60% - at DF. Analysis of influence of various factors (statistically significant) on the response to therapy is presented in the Table.Table.Influence of various factors on the response to therapy with denosumab after 12 months of treatment (n=66)DXA sitePositive response on therapy is associated withNegative response on therapy is associated withL1-L4–- GC intake (> 3 months in anamnesis) (р = 0,034);- the beginning of GC intake after menopause (р = 0,023)Hip neck- higher concentration of the RF (initially and in dynamics) (р < 0,05);- the beginning of menopause later than RA onset (р = 0,024)- GC intake (> 3 months in anamnesis) (р = 0,024)Forearm (distal 1/3)- RF-positivity (р = 0,02)- back correlates with increase in erosion score and total SVH score: r = –0,360 (р < 0,05)Conclusion:After 12 months of therapy with denosumab in postmenopausal women with RA and OP it was shown the significant increase of BMD in L1-L4 and HN, a tendency to increase in DF. The mean change of BMD (%) after 12 months was +4,6% at L1-L4, at HN +2,8%, at DF +0,7%. Positive response on denosumab (BMD) was noted in 89% patients at L1-L4, 67% - at HN and 60% - at DF. Analysis of influence of factors on the response to therapy showed that positive response on therapy in NH and DF was associated with RF-positivity. The distinct contribution to the negative response in L1-L4 and HN was associated with GC intake (previous intake more than 3 months in the anamnesis) and purpose of the GC after menopause onset. Also, negative response in DF back correlated with increase in erosion score and total SVH score.Disclosure of Interests:None declared

AB1130 LOCALIZATION OF MRI INFLAMMATORY LESIONS OF THE HAND IN SCLERODERMA AND RHEUMATOID ARTHRITIS - COMPARATIVE STUDY

Background:Inflammatory lesions of hand are frquent clinical feature in rheumatoid artritis (RA), with lower frequency in pts with systemic sclerosis (SSc), also. MR is useful method for detecting and quantification of inflammatory lesion of the hand (bone oedema, erosions, synovitis) in RA and SSc.Objectives:The aim of the study was to compare MR hand feature in SSc (experimental) and RA (control group) and to detect the localisation of the highest OMERACT RAMRISinflammatory score on the hand in pts with SSc and RAMethods:110 pts with SSc and 60 with RA were investigated (mean age 53y). All the pts underwenr clinical examination, X ray and MR on the dominant hand and wrist. Contrast enhanced low field MRI of the wrist and MCP2-5 joints was performend to all the pts. MRI inflammatory changes (bone oedema,erosions, synovitis)were assessed and scored by OMERACT RAMRIS scoring system.Results:Clinical examination confirmed synovitis in 17.1%, and 78% of patients with SSc using MR I (p <0.001). In the SSc group, erosions (by MR method) was confirmed in 52 (63.4%), by radiography in 22 pts (27.5%), which is a significantly lower percentage (p <0.001). In the control RA group, erosion was confirmed in 34 (97.1%) by MR method, and by radiography in 6 (17.1%), which is a statistically significant difference (p <0.001). Mean values of total MR score of synovitis (2.69 ± 2.29: 4.37 ± 1.31), oedema (6.58 ± 10.89: 20.57 ± 10.23) and erosion (6.84 ± 7, 43: 18.60 ± 5.01) on the wrist of the dominant hand were significantly higher in subjects with control RA than in those in the experimental SSc (p < 0.001). Mean values of total MR score of synovitis (3.15 ± 2.95: 5.26 ± 2.09), oedema (3.99 ± 9.82: 10, 51 ± 7.90) and erosion (4, 04 ± 4.76: 9.69 ± 4.27) on the MCP joints of the dominant hand were significantly higher in the control RA subjects (p <0.001).The highest OMERACR RAMRIS synovitis score was on distal radioulnar (DRU joint) of hand in SSc and also In RA pts. The highest erosion score was found on capitate bone in SSc, but in lunate bone in RA pts. The highest bone oedema score was also found on capitate bone in SSc, but in lunate bone in RA pts. According to the MCP joints, the highest synovitis score was found on the second finger in SSc and RA, highest erosion score also on the second finger in SSc, but on the third finger in RA; The highest bone oedema score was found on the third finger in SSc, and olso on the third and fifth finger in RA ptsConclusion:MR inflammatory lesions in SSc are less frequent compared to that in RA but still in significant percentage, confirming the need for early detection and aggressive treatment of both, RA and SSc patients with joint involvementReferences:[1]Avouac J, Walker UA, Hachulla E, Riemekasten G, Cuomo G, Carreira PE, et al. Joint and tendon involvement predict disease progression in systemic sclerosis: a EUSTAR prospective study. Annals of the rheumatic diseases. 2016;75(1):103–9.[2]Abdel-Magied RA, Lotfi A, AbdelGawad EA. Magnetic resonance imaging versus musculoskeletal ultrasonography in detecting inflammatory arthropathy in systemic sclerosis patients with hand arthralgia. Rheumatology international. 2013;33(8):1961–6.doi:10.1007/s00296-013-2665-8.Disclosure of Interests:None declared

Impending radiographic erosive progression over the following year in a cohort of consecutive patients with inflammatory polyarthritis: prediction by serum biomarkers

Background/PurposeTo evaluate biomarkers as predictors of impending erosion progression.MethodsVariables were measured at baseline and annually up to 5 years in patients with recent-onset polyarthritis treated to zero swollen joints. Erosive status was defined as ≥5 Units in Sharp/van der Heijde Erosion Score; Rapid Erosive Progression (REP) was defined as an increase ≥5 Units in Erosion Scores between consecutive visits. Generalised estimating equations (GEEs) evaluated the effect on REP of positive anticyclic citrullinated peptides (ACPAs) and/or rheumatoid factor (RF), C-reactive protein ˃8.0 mg/L (High-CRP) and 14-3-3η protein ≥0.50 ng/mL (High-14-3-3η), alone and in combinations.ResultsOut of 2155 evaluations in 749 consecutive patients, REP occurred after 186 (8.6%) visits, including 13 (2.2%) in patients recruited since 2010. Only 18/537 (3.4%; 6/411 (1.5%) in non-erosive vs 12/126 (9.5%) in patients already erosive) visits without any positive biomarker were followed by REP; at least one biomarker was positive prior to REP in 168/186 (90.3%) visits. Being positive for all four biomarkers conferred a positive predictive value (PPV) of 30.0% (RR 21.8) in patients non-erosive at the visit versus 35.5% (RR 3.07) in those already erosive. High-14-3-3η increased REP only in visits with High-CRP (eg, RR 2.5 to 3.9 when ACPA also positive) and in patients with non-erosive status (eg, RR from 4.3 to 9.4 when also High-CRP).ConclusionsAdding High-14-3-3η to positive antibodies and CRP improves prediction of impending REP. Although REP is becoming rarer, signatures of biomarkers might help to adapt treatment strategies in at-risk individuals, even those already erosive.