Our case highlights SARS-CoV-2 and pembrolizumab as trigger of secondary hemophagocytic lymphohistiocytosis. Although it is a rare complication, it must be suspected in order to start specific treatment. In this context, intravenous immunoglobulins could be a therapeutic option.
Background:Myositis-specific antibodies (MSA) are highly specific and useful to classify patients as having syndromes with distinct clinical features and prognosis. MSA are almost always mutually exclusive and quite specific, adding value as a useful biomarker for diagnosis. Although individual autoantibodies aren’t sensitive enough to detect the full spectrum of idiopathic inflammatory myopathies (IIM), the sensitivity of a myositis panel is increasing as more autoantibodies are discovered, and as better assays become available.Objectives:We aimed to analyze the usefulness of a myositis-specific immunoblot for the diagnosis of IIM in a hospital cohort from January 2019 to December 2020. We also seek to correlate immunological findings with the risk of associated interstitial lung disease (ILD), cancer, or death.Methods:Retrospective single-center observational study conducted in a Spanish tertiary hospital. In patients with high clinical suspicion of IIM, a myositis immunoblot was performed including Jo1, PL-7, PL-12, EJ, SRP, Mi2, Ku, MDA-5, TIF1-γ, HMGCR, PM-Scl and Ro52 antibodies. The demographic characteristics, the risk of ILD, cancer and death were analyzed.Results:In a cohort of 313 patients with high suspicion of IIM, 87 patients (27.8%) presented a positive MSA (MSA+ve). The mean age at diagnosis was 56.7±16.9 years, with no significant differences between MSA+ve and MSA-ve (p=0.597). Most of the patients were women with significant differences between both groups (80.5% MSA+ve vs 68.1% MSA-ve, p=0.030).IIM were classified as antisynthetase syndrome (ARS) (38%), dermatomyositis (DM) (31%), overlap myopathy (OM) (16.9%) and necrotizing myopathy (NM) (14.1%) according to the manifestations and MSA found (Jo1, PL-12, PL-7, EJ in ARS; Mi-2, MDA-5 and TIF1-γ in DM; Ku and PM-Scl in OM; HMGCR and SRP in NM). The most frequent MSA were anti-Jo1 (16.9%), TIF1-γ (15.5%), Ku (12.7%), Mi-2 (9.9%), PL-7 (9.9%), HMCGR (8.5%), PL-12 (7%), MDA-5 (5.6%), SRP (5.6%) and EJ (4.2%). The presence of Ro52 associated with other MSA was found in 20 patients (22.9%).ILD was the most frequent manifestation (45.2% of the MSA+ve). Non-specific interstitial pneumonia (NSIP) was the most frequent ILD (39.5%), followed by usual interstitial pneumonia (34.2%). The main risk factors associated with IIM-ILD were some subtypes of the MSAs (p<0.001), the association of Ro52 (p<0.001), and older age (p=0.027). Among the IIM, ARS and OM (p<0.001) were more frequently associated with IIM-ILD. The MSAs most associated with IIM-ILD were Jo1, PL-7, PM-Scl, Ku and SRP (p<0.001).Cancer was found in 9.6% of MSA+ve patients. The most frequent tumors were gynecological (37.5%), followed by gastrointestinal (25%) and breast cancer (12.5%). Factors associated with cancer were age (p=0.010), TIF1-γ (p<0.001), SRP (p=0.004), PL-12 (p=0.013), PL-7 (p=0.047) and HMGCR (p=0.027).The mortality of these patients was 3.5%. There were no differences regarding MSA+ve/-ve (p = 0.911). However, MDA-5 (p=0.033) and older age (p=0.001) were associated with higher mortality. There were no significant differences between the IIM classifications, the associated SAD, the presence of cancer or ILD. However, longer follow-up periods and future studies are necessary to confirm these results.Conclusion:The use of a myositis blot allowed classifying, stratifying the risk of ILD, the risk of cancer and the risk of mortality in IIM. IIM-ILD was the most frequent complication, usually manifested as NSIP. The associated risk factors were ARS, OM, some MSAs, Ro52+ and older age. Cancer was a serious and frequent manifestation in these patients, especially in patients with TIF1-γ and other MSAs, so it is essential to know the risk factors and perform an early screening, especially in older patients.A better knowledge of the serological profiles of IIM will provide more individualized approaches and better risk stratification, helping in the management and treatment of these patients.References:[1]Satoh et al. Clin Rev Allergy Immunol. 2017 Feb;52(1):1-19.[2]Betteridge et al. J Intern Med. 2016 Jul;280(1):8-23.Disclosure of Interests:None declared
No abstract
Background:Tocilizumab (TCZ) has shown to be effective for large vessel vasculitis including Takayasu arteritis (TAK) (1-3). Most evidence in TAK comes from Asian patients. However, white patients seem to have different clinical and prognostic features.Objectives:Our aims were to: a) assess the efficacy and safety of TCZ in white patients with refractory TAK, b) determine if clinical improvement correlates with imaging outcomes, c) compare TCZ in monotherapy (TCZMONO) vs combined with conventional immunosuppressive drugs (TCZCOMBO)Methods:Multicenter study of white patients with refractory TAK who received TCZ.Outcomes variables were remission, glucocorticoid-sparing effect, improvement in imaging techniques, and adverse events. A comparative study between patients who received TCZMONO and TCZCOMBO was performed.Results:54 patients (46 women/8 men; median age 42.0 [32.5-50.5] years). TCZ was started after 12.0 [3.0-31.5] months since TAK diagnosis. Remission was achieved in 12/54 (22.2%), 19/49 (38.8%), 23/44 (52.3%) and 27/36 (75%) at 1, 3, 6 and 12 months, respectively. Prednisone dose was reduced from 30.0 [12.5-50.0] to 5.0 [0.0-5.6] mg/day at 12 months (Table 1). 10 (26.3%) of the 38 patients in whom an imaging follow-up test was performed showed no radiographic improvement after a median of 9.0 [6.0-14.0] months. 4 of them were in clinical remission.23 (42.6%) patients were on TCZMONO and 31 (57.4%) on TCZCOMBO: MTX (n=28), cyclosporine A (n=2), azathioprine (n=1). Patients on TCZCOMBO were younger (38.0 [27.0-46.0] vs 45 [38.0-57.0] years; p= 0.048), with a trend to longer TAK duration (21.0 [6.0-38.0] vs 6.0 [1.0-23.0] months; p= 0.08) and higher C-reactive protein (2.4 [0.7-5.6] vs 1.3 [0.3-3.3] mg/dL; p=0.16). Despite these differences, similar outcomes were observed in both groups (log rank p=0.862) (Figure 1). Relevant adverse events were reported in 6 (11.1%) patients, but only 3 developed severe events that required TCZ withdrawal.Table 1.Baselinen=54Month 1N=54Month 3N=49Month 6N=44Month 12N=36Clinical remission, n (%)12 (22.2)19 (38.8)23 (52.3)27 (75.0)Laboratory improvementCRP (mg/dL), median [IQR]1.5 [0.5-3.5]0.2 [0.1-0.7]*0.2 [0.5-0.5]*0.2 [0.1-0.5]*0.1 [0.0-0.4]*ESR (mm/1sthour), median [IQR]30.5 [8.7-52.7]7.0 [3.0-14.0]*4.5 [2.0-8.0]*5.0[2.0-6.0]*4.0 [2.0-9.5]*Hemoglobin (g/dL), mean ± SD12.4 ±1.513.0 ±1.2*13.0 ±1.4*13.2 ±1.5*12.9 ±1.6*Prednisone dose, median [IQR]30.0 [12.5-50.0]20.0 [10.0-30.0]*10.0 [5.0-20.0]*5.0 [5.0-10.5]*5.0 [0.0-5.6]*CRP: C-Reactive Protein; ESR: Erythrocyte Sedimentation Rate; IQR: interquartile range; n: number. *p<0.01 vs baseline (Wilcoxon test).Conclusion:TCZ is effective and safe in white patients with refractory TAK. A discordance between clinical and imaging activity assessment may exist.References:[1]Prieto Peña D et al. Clin Exp Rheumatol 2020 Nov 27. PMID: 33253103.[2]Loricera J, et al. Clin Exp Rheumatol 2016; 34:S44-53. PMID: 27050507.[3]Calderón-Goercke M, et al. Semin Arthritis Rheum 2019; 49:126-35. PMID: 30655091Disclosure of Interests:Diana Prieto-Peña Grant/research support from: DP-P has received research support from UCB Pharma, Roche, Sanofi, Pfizer, AbbVie and Lilly., Pilar Bernabéu: None declared, Paloma Vela-Casasempere: None declared, J. Narváez: None declared, Carlos Fernández-López: None declared, Mercedes Freire González: None declared, Beatriz González-Alvarez: None declared, Roser Solans-Laqué: None declared, Jose Luis Callejas-Rubio: None declared, Norberto Ortego: None declared, Carlos Fernández-Díaz: None declared, Esteban Rubio Romero: None declared, SALVADOR GARCÍA MORILLO: None declared, Mauricio Minguez: None declared, Cristina Fernández-Carballido: None declared, Eugenio de Miguel: None declared, Sheila Melchor: None declared, Eva Salgado-Pérez: None declared, Beatriz Bravo: None declared, Susana Romero-Yuste: None declared, Juan Salvatierra: None declared, Cristina Hidalgo: None declared, Sara Manrique Arija: None declared, C. Romero-Gómez: None declared, Patricia Moya: None declared, Noelia Alvarez-Rivas: None declared, Javier Mendizabal: None declared, Francisco Miguel Ortiz Sanjuan: None declared, I. Pérez de Pedro: None declared, JOSE LUIS ALONSO VALDIVIESO: None declared, Pérez Sánchez Laura: None declared, Roldán Molina Rosa: None declared, Nagore Fernández-Llanio: None declared, Ricardo Gómez de la Torre: None declared, Silvia Suarez: None declared, María Jesús Montesa: None declared, Monica Delgado Sanchez: None declared, J. Loricera: None declared, Belén Atienza-Mateo: None declared, Santos Castañeda: None declared, Miguel A González-Gay Grant/research support from: MAG-G received grants/research supports from Abbvie, MSD, Jansen and Roche and had consultation fees/participation in company sponsored speaker´s bureau from Abbvie, Pfizer, Roche, Sanofi, Lilly, Celgene and MSD, Ricardo Blanco Grant/research support from: RB received grants/research supports from Abbvie, MSD and Roche, and had consultation fees/participation in company sponsored speaker´s bureau from Abbvie, Lilly, Pfizer, Roche, Bristol-Myers, Janssen, UCB Pharma and MSD.
BackgroundTocilizumab (TCZ) has shown to be effective for large vessel vasculitis including giant cell arteritis (GCA) and Takayasu arteritis (TAK) (1-5). However, LVV-GCA and TAK show different demographic and clinical features that may influence on TCZ therapeutic response.ObjectivesTo compare the effectiveness of TCZ in patients with LVV-GCA and patients with TAK.MethodsObservational multicenter study of patients with LVV-GCA and TAK who received TCZ. Outcome variables were: a) proportion of patients who achieved complete clinical improvement along with normalization of laboratory markers (CRP ≤0.5mg/dL and/or ESR ≤ 20 mm/1st hour) at 12 months b) complete improvement in imaging techniques. A comparative study between patients with LVV-GCA and TAK was performed.ResultsWe evaluated 70 LVV-GCA and 57 TAK patients who received TCZ. Main clinical and demographic characteristic are described in Table 1. Patients with TAK were younger, had longer disease duration, had received more commonly previous biologic therapy and were receiving higher doses of prednisone at baseline. TCZ intravenous administration was more common in TAK patients (80.7% vs 48.6%; p<0.01). Follow-up time after TCZ onset was similar in both groups. At 12 months, about 75% of patients achieved complete clinical improvement and ESR/CRP normalization in both groups. A follow-up imaging technique was performed in 37 LVV-GCA patients after a mean time of 12.9±6.0 months and 38 TAK patients after 9.5±5.0 months. Complete improvement in imaging techniques was only observed in 18.9% and 21.1% of patients with LVV-GCA and TAK, respectively (Figure 1).Table 1.LVV-GCA (n=70)TAK (n=57)pGeneral featuresAge (years), mean ± SD67.2 ± 10.540.5 ± 16.3< 0.01Sex (female), n (%)51 (72.9)49 (86)0.07Disease evolution before TCZ onset (months), median [IQR]5 [2-15]12 [3-37]<0.01Baseline laboratory parametersESR (mm/1st hour), median [IQR]32 [12.5-54.7]31 [10-52]0.82CRP (mg/dL), median [IQR]1.4 [0.5-2.4]1.4 [0.5-3.5]0.41Baseline prednisone dose (mg/day), median [IQR]15 [10-20]30 [15-50]< 0.01Previous therapyConventional DMARDs, n(%)45 (64.3)44(77.2)0.51Biologic therapy, n (%)0(0)12 (21.1)<0.01TCZ therapyIntravenous, n (%)34 (48.6)46 (80.7)< 0.01Combined with MTX, n(%)24 (34.3)24 (42.1)0.37Follow-up time after TCZ onset, median [IQR]20 [10-36]18 [7-41]0.73Complete clinical improvement and ESR/CRP normalization at 12 months, n/N (%)35/47 (74.4)30/39 (76.9)0.79Complete improvement in imaging techniques, n/N(%)7/37 (18.9)8/38 (21.1)0.85CRP: C-reactive protein; DMARDs: Disease-modifying anti-rheumatic drugs ESR: erythrocyte sedimentation rate; GCA: giant cell arteritis; IQR: interquartile range; LVV: large vessel; MTX: methotrexate; n: Number of patients; N: total number of patients: TCZ: tocilizumab; TAK:takayasuFigure 1.ConclusionThe effectiveness of TCZ was similar in patients with LVV-GCA and TAK, despite a more refractory disease in TAK patients. A discordance between clinical and imaging activity improvement was observed in both LVV-GCA and TAK, as reported in previous studies (3).References[1]Calderón-Goercke M, et al. Semin Arthritis Rheum 2019; 49:126-35. https://doi.org/10.1016/j.semarthrit.2019.01.003[2]Prieto-Peña D et al. Ther Adv Musculoskelet Dis. 2021;13:175. PMID: 34211589.[3]Prieto Peña D et al. Clin Exp Rheumatol. 2021;39 Suppl 129:69-75. PMID: 33253103.[4]González-Gay MA, et al. Expert Opin Biol Ther. 2019;19:65-72. doi: 10.1080/14712598.2019.1556256.[5]Prieto-Peña D, et al. Semin Arthritis Rheum. 2019;48(4):720-727. doi: 10.1016/j.semarthrit.2018.05.007Disclosure of InterestsNone declared
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