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1.
J Rheumatol ; 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33649069

RESUMO

OBJECTIVE: In Rheumatoid Arthritis (RA), evidence regarding the effectiveness of a second biologic Disease Modifying Anti-Rheumatic Drugs (bDMARDs) in patients whose first ever bDMARD was a non-tumor-necrosis-factor-inhibitor (TNFi) bDMARD is limited. The objective of this study was therefore to assess the outcome of the second bDMARD (non-TNFi [rituximab, abatacept or tocilizumab, separately] and TNFi) after failure of a non-TNFi bDMARD as first bDMARD. METHODS: We identified RA patients from the five Nordic biologics registers started treatment with a non-TNFi as first ever bDMARD but switched to a second bDMARD. For the second bDMARD, we assessed survival-on-drug (at 6 and 12 months), and primary response (at 6 months). RESULTS: We included 620 patients starting a second bDMARD (ABA 86, RTX 40, TCZ 67 and TNFi 427) following failure of a first non-TNFI bDMARD. At 6 and 12 months after start of their second bDMARD, around 70% and 50%, respectively, remained on treatment, and at 6 months less than one third of patients were still on their second bDMARD and had reached low disease activity or remission according to DAS28. For those patients whose second bMDARD was a TNFI, the corresponding proportion was slightly higher (40%). CONCLUSION: The survival-on-drug and primary response of a second bDMARD in RA patients switching due to failure of a non-TNFi bDMARD as first bDMARD is modest. Some patients may benefit from TNFi when used after failure of a non-TNFi as first bDMARD.

2.
Ann Rheum Dis ; 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33622688

RESUMO

OBJECTIVES: To estimate absolute and relative risks for all-cause mortality and for severe COVID-19 in inflammatory joint diseases (IJDs) and with antirheumatic therapies. METHODS: Through Swedish nationwide multiregister linkages, we selected all adult patients with rheumatoid arthritis (RA, n=53 455 in March 2020), other IJDs (here: spondyloarthropathies, psoriatic arthritis and juvenile idiopathic arthritis, n=57 112), their antirheumatic drug use, and individually matched population referents. We compared annual all-cause mortality March-September 2015 through 2020 within and across cohorts, and assessed absolute and relative risks for hospitalisation, admission to intensive care and death due to COVID-19 March-September 2020, using Cox regression. RESULTS: During March-September 2020, the absolute all-cause mortality in RA and in other IJDs was higher than 2015-2019, but relative risks versus the general population (around 2 and 1.5) remained similar during 2020 compared with 2015-2019. Among patients with IJD, the risks of hospitalisation (0.5% vs 0.3% in their population referents), admission to intensive care (0.04% vs 0.03%) and death (0.10% vs 0.07%) due to COVID-19 were low. Antirheumatic drugs were not associated with increased risk of serious COVID-19 outcomes, although for certain drugs, precision was limited. CONCLUSIONS: Risks of severe COVID-19-related outcomes were increased among patients with IJDs, but risk increases were also seen for non-COVID-19 morbidity. Overall absolute and excess risks are low and the level of risk increases are largely proportionate to those in the general population, and explained by comorbidities. With possible exceptions, antirheumatic drugs do not have a major impact on these risks.

3.
Mediterr J Rheumatol ; 31(Suppl 2): 247-252, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33196000

RESUMO

As the worldwide burden of COVID-19 increases exponentially, healthcare systems are plagued by unprecedented pressure. In this setting, many rheumatologists across the globe have been recruited to support the front line, facing several unexpected challenges, but also providing valuable skills in combating COVID-19. At the same time, the rheumatic disease patient population may be especially vulnerable to such a rapidly contagious infectious disease and thus needs care and support that has to be provided quickly and efficiently. Clear advice on viral spread mitigation, precise guidelines on immunosuppressive treatment use and alternative methods of providing care, such as telemedicine, are a few of the rheumatologists' new challenges in caring for their patients in the COVID-19 era. Finally, among other specialties, rheumatologists hold a unique place in the fight against the hyper-inflammatory state caused by severe SARS-CoV-2 infection, leading to increased morbidity and mortality. Given their vast experience in the use of biologic and targeted therapies, rheumatologists should lead the way in developing reliable scientific evidence for the optimal treatment of severe COVID-19.

4.
Clin Rheumatol ; 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-32989505

RESUMO

Immunotherapy has revolutionized cancer treatment during the last years. Several monoclonal antibodies that are specific for regulatory checkpoint molecules, that is, immune checkpoint inhibitors (ICIs), have been approved and are currently in use for various types of cancer in different lines of treatment. Cancer immunotherapy aims for enhancing the immune response against cancer cells. Despite their high efficacy, ICIs are associated to a new spectrum of adverse events of autoimmune origin, often referred to as immune-related adverse events (irAEs), which limit the utility of these drugs. These irAEs are quite common and can affect almost every organ. The grade of toxicity varies from very mild to life-threatening. The pathophysiological mechanisms behind these events are not fully understood. In this review, we will summarize current evidence specifically regarding the rheumatic irAEs and we will focus on current and future treatment strategies. Treatment guidelines largely support the use of glucocorticoids as first-line therapy, when symptomatic therapy is not efficient, and for more persistent and/or moderate/severe degree of inflammation. Targeted therapies are higher up in the treatment pyramid, after inadequate response to glucocorticoids and conventional, broad immunosuppressive agents, and for severe forms of irAEs. However, preclinical data provide evidence that raise concerns regarding the potential risk of impaired antitumoral effect. This potential risk of glucocorticoids, together with the high efficacy and potential synergistic effect of newer, targeted immunomodulation, such as tumor necrosis factor and interleukin-6 blockade, could support a paradigm shift, where more targeted treatments are considered earlier in the treatment sequence.

6.
RMD Open ; 6(2)2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32917833

RESUMO

BACKGROUND: Rheumatoid arthritis (RA)-associated anticitrullinated protein/peptide antibodies (ACPA) might originate at mucosal sites such as the lungs. We aimed to examine the relationship between the ACPA repertoire and lung abnormalities on high-resolution CT (HRCT) in patients with earlyuntreated RA. METHODS: 106 patients with newly diagnosed untreated RA were examined with HRCT of the lungs. Blood samples were analysed for presence of rheumatoid factor (RF) and ACPA using either a CCP2 detection kit or an immunochip containing 10 different citrullinated peptides. Association between HRCT findings and the antibody repertoire was assessed by logistic regression analysis. RESULTS: The number (%) of patients with HRCT abnormalities was 58 (54.7%) for parenchymal abnormalities and 68 (64.2%) for airway abnormalities. CCP2 IgG, RF IgA and antibodies against citrullinated fibrinogen were associated with the presence of parenchymal lung abnormalities. Interestingly, a high number of ACPA fine specificities gave a high risk of having parenchymal lung abnormalities at the time of RA diagnosis. No significant signals were identified between ACPA specificities and risk for airway abnormalities. CONCLUSIONS: The presence of RF and ACPAs (especially against citrullinated fibrinogen peptides) as well as high number of ACPAs fine specificities are associated with parenchymal lung abnormalities in patients with early, untreated RA. This provides further support for an important pathogenic link between the lung and systemic autoimmunity, contributing to RA development.

9.
J Clin Med ; 9(6)2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32532059

RESUMO

Impaired health-related quality of life (HRQoL) is a major problem in patients with systemic lupus erythematosus (SLE). Antimalarial agents (AMA) are the cornerstone of SLE therapy, but data on their impact on HRQoL are scarce. We investigated this impact using baseline data from the BLISS-52 (NCT00424476) and BLISS-76 (NCT00410384) trials (n = 1684). HRQoL was self-reported using the Medical Outcomes Study short-form 36 (SF-36), functional assessment of chronic illness therapy (FACIT)-Fatigue and 3-level EuroQoL 5-Dimension (EQ-5D) questionnaires. Patients on AMA (n = 1098/1684) performed better with regard to SF-36 physical component summary, physical functioning, role physical, bodily pain, FACIT-Fatigue, EQ-5D utility index and EQ-5D visual analogue scale scores. The difference in SF-36 physical functioning (mean ± standard deviation (SD): 61.1 ± 24.9 versus 55.0 ± 26.5; p < 0.001) exceeded the minimal clinically important difference (≥5.0). This association remained significant after adjustment for potential confounding factors in linear regression models (standardised coefficient, ß = 0.07; p = 0.002). Greater proportions of AMA users than non-users reported no problems in the mobility, self-care, usual activities and anxiety/depression EQ-5D dimensions. AMA use was particularly associated with favourable HRQoL in physical aspects among patients with active mucocutaneous and musculoskeletal disease, and mental aspects among patients with active renal SLE. These results provide support in motivating adherence to AMA therapy. Exploration of causality in the relationship between AMA use and favourable HRQoL in SLE has merit.

11.
12.
Mediterr J Rheumatol ; 31(1): 87-91, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32411939

RESUMO

The therapeutic armamentarium in Systemic Lupus Erythematosus (SLE) is expanding with the introduction of novel biologic and small-molecule agents. Complementary to randomized controlled trials, registry-based studies are advantageous due to the inclusion of a wider range of patients from daily practice and the potential for long-term monitoring of the efficacy and safety of therapies. Moreover, data from registries can be used to identify disease phenotypes that best respond to biologic agents, and to correlate clinical response with parameters such as co-administered therapies and comorbidities. In this project, we will use the configuration of the Hellenic Registry of Biologic Therapies for inflammatory arthritides in order to design a dedicated SLE module with variables pertaining to global and organ-specific disease activity, severity, flares, organ damage/outcome, comorbidities and adverse events. The second stage will involve the pilot implementation of this platform for the multicentric registration of SLE patients who are treated with belimumab. The significance lies in the development of a structured registry that enables the assessment of the disease burden and the long-term efficacy and safety of existing and future biological agents in SLE. Piloting the registry can serve as a basis for establishing nationwide collaborative efforts.

13.
Clin Rheumatol ; 39(3): 957-961, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31836935

RESUMO

Extra-articular manifestations are common in rheumatoid arthritis (RA), with lung involvement being one of the commonest. Apart from interstitial lung disease which is a well-recognized manifestation, it seems that lung cancer has also increased frequency in RA. In fact, recent meta-analyses have suggested that in RA compared with the general population, lymphomas and lung malignancy are more frequent. For the latter, male gender, seropositivity for rheumatoid factor and/or anti-citrullinated protein antibody (ACPA), as well as older age, has been suggested, among others, as risk factors. Several hypotheses have been formulated to explain the increased frequency of lung cancer in RA. These include smoking and/or interstitial lung as common risk factors for both RA and lung cancer and chronic inflammation predisposing to malignant diseases. Numerous questions remain to be answered. For example, are there any risk factors (e.g., positivity for rheumatoid factor or anti-citrullinated peptide antibodies) that would predict the development of lung cancer in these patients? Are there any screening procedures appropriate for early diagnosis and therefore better outcome? Data from large registries are needed to better define the profile of these patients.

14.
Clin Exp Rheumatol ; 38(5): 841-847, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31820726

RESUMO

OBJECTIVES: Early identification of patients with rheumatoid arthritis (RA) is essential to allow prompt therapy. In this study, we aimed to evaluate the performance of the newly proposed ERA criteria, compared to the 1987 ACR and 2010 ACR/EULAR criteria in an international multicentre study. METHODS: A total of 606 patients with disease duration ≤2 years and age ≥16 years who were diagnosed as RA or non-RA were enrolled from China, Sweden and India. The clinical and laboratory parameters were recorded. We compared the sensitivity, specificity, predictive value, likelihood ratio (LR), and the area under the ROC curve (AUC) of three criteria in these cohorts. Concordance between the three criteria was calculated with the Kappa coefficient. RESULTS: Three hundred and twelve RA and 294 non-RA patients were included. The Early Rheumatoid Arthritis (ERA) criteria had significantly higher specificity compared to the 2010 ACR/ EULAR criteria (83.7% vs. 78.2%, p=0.02) and sensitivity were similar (79.2% vs. 78.5%, p=0.883). In comparison with the 1987 ACR criteria, the ERA criteria had higher sensitivity (79.2% vs. 54.5%, p<0.001) but lower specificity (83.7% vs. 89.1%, p<0.001), and the AUC of the ERA criteria (0.878) was comparable to the 2010 ACR/EULAR criteria (0.849) and higher than the 1987 ACR criteria (0.791, p<0.0001). Patients from the three countries, seronegative and very early arthritis cohorts yielded consistent results. CONCLUSIONS: The ERA criteria demonstrate a better performance across ethnics in early RA diagnosis, and is more feasible in daily practice.


Assuntos
Artrite Reumatoide , Área Sob a Curva , Artrite Reumatoide/diagnóstico , Humanos , Índia , Sensibilidade e Especificidade , Suécia
16.
RMD Open ; 5(2): e000993, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31413870

RESUMO

Treatment of rheumatoid arthritis (RA) has improved substantially during the last decades, mainly due to the development and introduction in everyday practice of new, highly efficacious, disease-modifying antirheumatic drugs (DMARDs), more optimal usage of them, earlier diagnosis and tighter control of disease activity targeting at remission. Methotrexate is still today the anchor drug and the first-line treatment after diagnosis. However, numerous studies comparing methotrexate and biologic DMARDs, as well as new targeted synthetic DMARDs, both in early as in more established disease, have shown consistently better efficacy of the latter compared with methotrexate, with methotrexate yielding remission to maximum half of patients. This could suggest a new paradigm shift with earlier start of a biologic or a targeted synthetic DMARD, with the possibility of subsequent discontinuation in case of achievement of stable remission. Several strategy trials, however, have shown that there might be a clinical and structural benefit of initial, aggressive therapy, possibly even associated with higher chance of remaining in remission, after cessation of the biologic DMARD and continuing with methotrexate alone, but they have failed to show a clear advantage of such an aggressive treatment strategy. This might become a valuable option for the future treatment algorithm of RA, especially for a subgroup of patients with RA, but further confirmation from future research is needed. The crucial role of glucocorticoid use as part of the combination strategy should be acknowledged, and strategy trials should include this combination as an active comparator.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Metotrexato/uso terapêutico , Indução de Remissão/métodos , Artrite Reumatoide/metabolismo , Artrite Reumatoide/patologia , Produtos Biológicos/uso terapêutico , Biomarcadores/sangue , Quimioterapia Combinada/métodos , Glucocorticoides/uso terapêutico , Humanos , Fatores Imunológicos/uso terapêutico , Terapia de Alvo Molecular/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto , Inibidores do Fator de Necrose Tumoral/uso terapêutico
17.
J Diabetes Res ; 2019: 2936962, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31214621

RESUMO

Objective: Hypoxia is central in the pathogenesis of diabetic retinopathy (DR). Hypoxia-inducible factor-1 (HIF-1) is the key mediator in cellular oxygen homeostasis that facilitates the adaptation to hypoxia. HIF-1 is repressed by hyperglycemia contributing by this to the development of complications in diabetes. Recent work has shown that the HIF-1A Pro582Ser polymorphism is more resistant to hyperglycemia-mediated repression, thus protecting against the development of diabetic nephropathy. In this study, we have investigated the effect of the HIF-1A Pro582Ser polymorphism on the development of DR and further dissected the mechanisms by which the polymorphism confers a relative resistance to the repressive effect of hyperglycemia. Research Design and Method: 703 patients with type 1 diabetes mellitus from one endocrine department were included in the study. The degree of retinopathy was correlated to the HIF-1A Pro582Ser polymorphism. The effect of glucose on a stable HIF-1A construct with a Pro582Ser mutation was evaluated in vitro. Results: We identified a protective effect of HIF-1A Pro582Ser against developing severe DR with a risk reduction of 95%, even when adjusting for known risk factors for DR such as diabetes duration, hyperglycemia, and hypertension. The Pro582Ser mutation does not cancel the destabilizing effect of glucose but is followed by an increased transactivation activity even in high glucose concentrations. Conclusion: The HIF-1A genetic polymorphism has a protective effect on the development of severe DR. Moreover, the relative resistance of the HIF-1A Pro582Ser polymorphism to the repressive effect of hyperglycemia is due to the transactivation activity rather than the protein stability of HIF-1α.


Assuntos
Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/fisiopatologia , Retinopatia Diabética/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Idoso de 80 Anos ou mais , Glicemia/análise , Nefropatias Diabéticas/genética , Feminino , Genótipo , Glucose/análise , Células HEK293 , Humanos , Hiperglicemia/genética , Hiperglicemia/fisiopatologia , Hipóxia , Masculino , Pessoa de Meia-Idade , Mutação , Prolina/genética , Fatores de Risco , Serina/genética , Ativação Transcricional , Adulto Jovem
18.
Rheumatology (Oxford) ; 58(12): 2170-2176, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31157891

RESUMO

OBJECTIVES: To identify predictors of low disease activity and clinical remission following belimumab treatment in SLE. METHODS: SLE patients who received belimumab 10 mg/kg (N = 563) in the BLISS-52 and BLISS-76 clinical trials were surveyed. The performance of baseline factors in predicting attainment of low disease activity (defined as Lupus Low Disease Activity State) or clinical remission [defined as clinical (c)SLEDAI-2K = 0] at week 52 from treatment initiation was evaluated using logistic regression. Organ damage was assessed using the SLICC/ACR Damage Index (SDI). RESULTS: We demonstrated a negative impact of established organ damage on attainment of Lupus Low Disease Activity State [SDI > 0; odds ratio (OR): 0.44; 95% CI 0.22, 0.90; P = 0.024] and the primary Lupus Low Disease Activity State condition, i.e. SLEDAI-2K ⩽ 4 with no renal activity, pleurisy, pericarditis or fever (SDI > 1; OR: 0.46; 95% CI 0.27, 0.77; P = 0.004); cognitive impairment/psychosis was found to mainly account for the latter association. Baseline SDI scores > 1 predicted failure to attain cSLEDAI-2K = 0 (OR: 0.53; 95% CI 0.30, 0.94; P = 0.030), with cutaneous damage mainly driving this association. Anti-dsDNA positivity increased (OR: 1.82; 95% CI 1.08, 3.06; P = 0.025) and cardiovascular damage reduced (OR: 0.13; 95% CI 0.02, 0.97; P = 0.047) the probability of attaining cSLEDAI-2K = 0 along with a daily prednisone equivalent intake restricted to ⩽7.5 mg. CONCLUSION: Belimumab might be expected to be more efficacious in inducing low disease activity and clinical remission in SLE patients with limited or no organ damage accrued prior to treatment initiation. Patients with positive anti-dsDNA titres might be more likely to achieve clinical remission along with limited or no CS use.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Adulto , Anticorpos Antinucleares/imunologia , DNA/imunologia , Feminino , Febre/etiologia , Glucocorticoides/uso terapêutico , Hematúria/etiologia , Humanos , Modelos Logísticos , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Pericardite/etiologia , Pleurisia/etiologia , Prednisona/uso terapêutico , Prognóstico , Proteinúria/etiologia , Piúria/etiologia , Indução de Remissão , Índice de Gravidade de Doença , Adulto Jovem
20.
Mediterr J Rheumatol ; 30(2): 103-109, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32185349
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