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1.
RMD Open ; 7(1)2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33526709

RESUMO

OBJECTIVE: Interleukin (IL)-6 is a pleiotropic cytokine involved in the pathophysiology of rheumatoid arthritis (RA). Sirukumab is a human monoclonal antibody that binds to IL-6 with high affinity and specificity. METHODS: This long-term extension (LTE) study of the SIRROUND-D and SIRROUND-T studies assessed long-term safety and efficacy of sirukumab in adults with moderate-to-severe RA refractory to conventional disease-modifying antirheumatic drug therapy or antitumor necrosis factor agents. Patients received sirukumab 100 mg subcutaneously (SC) every 2 weeks (q2w) or sirukumab 50 mg SC every 4 weeks (q4w). RESULTS: 1820 patients enrolled in the LTE; median exposure was 2.34 and 2.07 years in sirukumab 50 mg q4w and 100 mg q2w groups, respectively. Adverse events (AEs) occurred in similar proportions between groups, with the exception of major adverse cardiovascular events (MACE), which were more common in the 50 mg q4w versus 100 mg q2w group (2.2% vs 1.0%), and injection-site reactions, more common in the 100 mg q2w group versus 50 mg q4w group (7.5% vs 3.7%). The most common serious AEs were infections (10% of the patients); 32 (1.8%) patients died during the study (primarily from serious infection and MACE). Malignancies were reported in 24 (1.3%) patients. Gastrointestinal perforations, hepatobiliary abnormalities and changes in laboratory parameters were rare. Reductions in RA signs and symptoms and improvements in physical function were maintained throughout the LTE. CONCLUSIONS: The safety profile of sirukumab in the LTE remained consistent with that reported in SIRROUND-D and SIRROUND-T and efficacy was maintained. TRIAL REGISTRATION NUMBER: NCT01856309.

2.
Ann Rheum Dis ; 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33436384

RESUMO

OBJECTIVES: To determine whether clinical tenderness can be considered a sign of inflammatory joint activity in patients with rheumatoid arthritis (RA), osteoarthritis (OA) or psoriatic arthritis (PsA) and to assess other possible factors associated with tenderness. METHODS: Patients diagnosed with RA, PsA and OA underwent clinical and ultrasound examination of wrists and finger joints. Radiographs of the hands were scored for erosions, joint space narrowing (JSN), osteophytes and malalignment. A binary damage score (positive if ≥1 erosion, JSN and/or presence of malalignment) was calculated. Differences in grey scale signs of synovitis and power Doppler (PD) between tender non-swollen (TNS) versus non-tender non-swollen (NTNS) joints were calculated. Disease duration was assessed,<2 years was regarded as early and >5 years as long-standing arthritis. RESULTS: In total, 34 patients (9 early and 14 long-standing) from patients with RA, 31 patients (7 early and 15 long-standing) with PsA and 30 with OA were included. We found equal frequencies of PD signal between TNS and NTNS joints in RA (p=0.18), PsA (p=0.59) or OA (p=0.96). However, PD had a significant association with tenderness in early arthritis both in RA (p=0.02) and in PsA (p=0.02). The radiographic damage score showed significant association with tenderness in RA (p<0.01), PsA (p<0.01) and OA (p=0.04). CONCLUSION: Tenderness might not always be a sign of active inflammation in RA, PsA and OA. While tenderness in early arthritis may be more related to inflammation, established disease is better explained by joint damage and malalignment.

3.
Ann Rheum Dis ; 2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33355152

RESUMO

BACKGROUND: Non-adherence to treatment could preclude reaching an optimal outcome. Thirty to 80% of patients with rheumatic and musculoskeletal diseases (RMDs) do not adhere to the agreed treatment. OBJECTIVES: The objective was to establish points to consider (PtCs) for the prevention, screening, assessment and management of non-adherence to (non-)pharmacological treatments in people with RMDs. METHODS: An EULAR task force (TF) was established, and the EULAR standardised operating procedures for the development of PtCs were followed. The TF included healthcare providers (HCPs), comprising rheumatologists, nurses, pharmacists, psychologists, physiotherapists, occupational therapists and patient-representatives from 12 European countries. A review of systematic reviews was conducted in advance to support the TF in formulating the PtCs. The level of agreement among the TF was established by anonymous online voting. RESULTS: Four overarching principles and nine PtCs were formulated. The PtCs reflect the phases of action on non-adherence. HCPs should assess and discuss adherence with patients on a regular basis and support patients to treatment adherence. As adherence is an agreed behaviour, the treatment has to be tailored to the patients' needs. The level of agreement ranged from 9.5 to 9.9 out of 10. CONCLUSIONS: These PtCs can help HCPs to support people with RMDs to be more adherent to the agreed treatment plan. The basic scheme being prevent non-adherence by bonding with the patient and building trust, overcoming structural barriers, assessing in a blame-free environment and tailoring the solution to the problem.

4.
Ann Rheum Dis ; 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33158881

RESUMO

OBJECTIVES: Janus kinase inhibitors (JAKi) have been approved for use in various immune-mediated inflammatory diseases. With five agents licensed, it was timely to summarise the current understanding of JAKi use based on a systematic literature review (SLR) on efficacy and safety. METHODS: Existing data were evaluated by a steering committee and subsequently reviewed by a 29 person expert committee leading to the formulation of a consensus statement that may assist the clinicians, patients and other stakeholders once the decision is made to commence a JAKi. The committee included patients, rheumatologists, a gastroenterologist, a haematologist, a dermatologist, an infectious disease specialist and a health professional. The SLR informed the Task Force on controlled and open clinical trials, registry data, phase 4 trials and meta-analyses. In addition, approval of new compounds by, and warnings from regulators that were issued after the end of the SLR search date were taken into consideration. RESULTS: The Task Force agreed on and developed four general principles and a total of 26 points for consideration which were grouped into six areas addressing indications, treatment dose and comedication, contraindications, pretreatment screening and risks, laboratory and clinical follow-up examinations, and adverse events. Levels of evidence and strengths of recommendations were determined based on the SLR and levels of agreement were voted on for every point, reaching a range between 8.8 and 9.9 on a 10-point scale. CONCLUSION: The consensus provides an assessment of evidence for efficacy and safety of an important therapeutic class with guidance on issues of practical management.

5.
RMD Open ; 6(3)2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33161377

RESUMO

OBJECTIVE: To analyse how non-adherence to prescribed treatments might be prevented, screened, assessed and managed in people with rheumatic and musculoskeletal diseases (RMDs). METHODS: An overview of systematic reviews (SR) was performed in four bibliographic databases. Research questions focused on: (1) effective interventions or strategies, (2) associated factors, (3) impact of shared decision making and effective communication, (4) practical things to prevent non-adherence, (5) effect of non-adherence on outcome, (6) screening and assessment tools and (7) responsible healthcare providers. The methodological quality of the reviews was assessed using AMSTAR-2. The qualitative synthesis focused on results and on the level of evidence attained from the studies included in the reviews. RESULTS: After reviewing 9908 titles, the overview included 38 SR on medication, 29 on non-pharmacological interventions and 28 on assessment. Content and quality of the included SR was very heterogeneous. The number of factors that may influence adherence exceed 700. Among 53 intervention studies, 54.7% showed a small statistically significant effect on adherence, and all three multicomponent interventions, including different modes of patient education and delivered by a variety of healthcare providers, showed a positive result in adherence to medication. No single assessment provided a comprehensive measure of adherence to either medication or exercise. CONCLUSIONS: The results underscore the complexity of non-adherence, its changing pattern and dependence on multi-level factors, the need to involve all stakeholders in all steps, the absence of a gold standard for screening and the requirement of multi-component interventions to manage it.

6.
Ann Rheum Dis ; 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004335

RESUMO

BACKGROUND: Despite treatment according to the current management recommendations, a significant proportion of patients with rheumatoid arthritis (RA) remain symptomatic. These patients can be considered to have 'difficult-to-treat RA'. However, uniform terminology and an appropriate definition are lacking. OBJECTIVE: The Task Force in charge of the "Development of EULAR recommendations for the comprehensive management of difficult-to-treat rheumatoid arthritis" aims to create recommendations for this underserved patient group. Herein, we present the definition of difficult-to-treat RA, as the first step. METHODS: The Steering Committee drafted a definition with suggested terminology based on an international survey among rheumatologists. This was discussed and amended by the Task Force, including rheumatologists, nurses, health professionals and patients, at a face-to-face meeting until sufficient agreement was reached (assessed through voting). RESULTS: The following three criteria were agreed by all Task Force members as mandatory elements of the definition of difficult-to-treat RA: (1) Treatment according to European League Against Rheumatism (EULAR) recommendation and failure of ≥2 biological disease-modifying antirheumatic drugs (DMARDs)/targeted synthetic DMARDs (with different mechanisms of action) after failing conventional synthetic DMARD therapy (unless contraindicated); (2) presence of at least one of the following: at least moderate disease activity; signs and/or symptoms suggestive of active disease; inability to taper glucocorticoid treatment; rapid radiographic progression; RA symptoms that are causing a reduction in quality of life; and (3) the management of signs and/or symptoms is perceived as problematic by the rheumatologist and/or the patient. CONCLUSIONS: The proposed EULAR definition for difficult-to-treat RA can be used in clinical practice, clinical trials and can form a basis for future research.

8.
Artigo em Inglês | MEDLINE | ID: mdl-32844216

RESUMO

OBJECTIVE: To determine the extent to which disease duration, alone or in combination with other baseline clinical and non-clinical factors, explains variations in outcome of tocilizumab initiated in biologic-naïve patients with established RA. METHODS: In this pooled analysis of phase 3 and 4 clinical trials conducted by the sponsor, predictors of response, including demographics, disease characteristics at baseline (start of tocilizumab dosing) and study characteristics (e.g. patient inclusion criteria, tocilizumab dosing regimen) were evaluated. Response was measured as change from baseline to week 24 in Clinical Disease Activity Index (CDAI) and HAQ-Disability Index (HAQ-DI) scores and as the proportions of patients who experienced ≥50% improvement based on ACR criteria (ACR50) and CDAI remission (≤2.8) rates at week 24. RESULTS: Improvements in all outcomes investigated were observed in patients receiving tocilizumab. Although disease duration was statistically significant in the models, it accounted for <2% of variation in CDAI and HAQ-DI score changes from baseline to week 24; baseline CDAI and HAQ-DI values accounted for 32% and 15% of variations, respectively. Doubling of disease duration reduced the odds of achieving an ACR50 response by only 9%, and each additional 5-year period of disease duration decreased the odds of achieving CDAI remission by only 15%. CONCLUSION: RA duration, alone or in combination with other baseline characteristics, had a statistically significant but clinically small effect on the outcomes of tocilizumab initiated in biologic-naïve patients with established RA.

9.
Clin Chem ; 66(11): 1405-1413, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32777031

RESUMO

BACKGROUND: In the context of the COVID-19 pandemic, numerous new serological test systems for the detection of anti-SARS-CoV-2 antibodies rapidly have become available. However, the clinical performance of many of these is still insufficiently described. Therefore, we compared 3 commercial CE-marked, SARS-CoV-2 antibody assays side by side. METHODS: We included a total of 1154 specimens from pre-COVID-19 times and 65 samples from COVID-19 patients (≥14 days after symptom onset) to evaluate the test performance of SARS-CoV-2 serological assays by Abbott, Roche, and DiaSorin. RESULTS: All 3 assays presented with high specificities: 99.2% (98.6-99.7) for Abbott, 99.7% (99.2-100.0) for Roche, and 98.3% (97.3-98.9) for DiaSorin. In contrast to the manufacturers' specifications, sensitivities only ranged from 83.1% to 89.2%. Although the 3 methods were in good agreement (Cohen's Kappa 0.71-0.87), McNemar tests revealed significant differences between results obtained from Roche and DiaSorin. However, at low seroprevalences, the minor differences in specificity resulted in profound discrepancies of positive predictive values at 1% seroprevalence: 52.3% (36.2-67.9), 77.6% (52.8-91.5), and 32.6% (23.6-43.1) for Abbott, Roche, and DiaSorin, respectively. CONCLUSION: We found diagnostically relevant differences in specificities for the anti-SARS-CoV-2 antibody assays by Abbott, Roche, and DiaSorin that have a significant impact on the positive predictive values of these tests.


Assuntos
Betacoronavirus/imunologia , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Anticorpos Antivirais/sangue , Automação Laboratorial , Estudos Transversais , Reações Falso-Positivas , Humanos , Imunoglobulina G/sangue , Limite de Detecção , Pandemias , Estudos Prospectivos , Curva ROC , Sensibilidade e Especificidade
10.
Patient Prefer Adherence ; 14: 949-961, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606613

RESUMO

Objective: Qualitative research exploring patient preferences regarding the mode of treatment administration for psoriatic arthritis (PsA) is limited. We report patient preferences and their reasons across PsA treatment modes. Methods: In this global, cross-sectional, qualitative study, interviews were conducted with adult patients with PsA in Brazil, France, Germany, Italy, Spain, the UK, and the US. Patients were currently taking a disease-modifying antirheumatic drug (DMARD). Patients indicated the order and strength of preference (0-100; 100 = strongest) across four modes of treatment administration: oral (once daily), self-injection (weekly), clinic injection (weekly), and infusion (monthly); reasons for preferences were qualitatively assessed. Descriptive statistics were reported. Fisher's exact tests and t-tests were conducted for treatment mode outcomes. Results: Overall, 85 patients were interviewed (female, 60.0%; mean age, 49.8 years). First-choice ranking (%) and mean [standard deviation] preference points were: oral (49.4%; 43.9 [31.9]); self-injection (34.1%; 32.4 [24.8]); infusion (15.3%; 14.5 [20.0]); clinic injection (1.2%; 9.2 [10.0]). Of 48 (56.5%) patients with a strong first-choice preference (ie point allocation ≥60), 66.7% chose oral administration. Self-injection was most often selected as second choice (51.8%), clinic injection as third (49.4%), and infusion as fourth (47.1%). Oral administration was the first-choice preference in the US (88.0% vs 38.0% in Europe). The most commonly reported reason for oral administration as the first choice was speed and ease of administration (76.2%); for self-injection, this was convenience (75.9%). The most commonly reported reason for avoiding oral administration was concern about possible drug interactions (63.6%); for self-injection, this was a dislike of needles or the injection process (66.7%). Conclusion: Patients with PsA preferred oral treatment administration, followed by self-injection; convenience factors were common reasons for these preferences. Overall, 43.5% of patients did not feel strongly about their first-choice preference and may benefit from discussions with healthcare professionals about PsA treatment administration options.

11.
Ther Adv Musculoskelet Dis ; 12: 1759720X20933489, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32612711

RESUMO

Aims: The aim of this study was to evaluate the implication of doubtful joint swelling on clinical examination with respect to objective markers of synovitis by ultrasound (US) in patients with rheumatoid arthritis (RA). Methods: Two independent observers performed a modified 28 swollen joint assessment (28SJC), in which joints could be graded as either definitely swollen, non-swollen, or doubtfully swollen. Two examiners blinded to clinical information performed US assessment of the hands. We performed descriptive statistics and models to analyse the links between clinical assessment and objective markers of inflammation. Results: A total of 1204 joints were evaluated in 43 RA patients; 93% (40/43) of patients had ⩾1 joint with doubtful swelling (range: 0-4/patient). Inter-reader reliability for the modified 28SJC was good (0.74). Generally, both grey scale (GS) and power Doppler (PD) discriminated across not swollen, doubtful, and swollen joints. GS signals discriminated better than PD between doubtful swelling and no swelling [odds ratio (OR) for GS: 5.2; 95% confidence interval (CI) 1.2-23.3 versus OR for PD 1.7; 95% CI 0.2-13.0], whereas PD discriminated better than GS between swelling and doubtful swelling (OR for PD: 28.7; 95% CI 3.6-228.2 versus GS: 1.7; 95% CI 0.3-8.4). Joint osteophytes did not increase the degree of doubtfulness. Conclusion: Clinical doubt in the assessment of joint swelling constitutes an intermediate state between unequivocal swelling and the lack thereof also regarding the objectively quantified level of inflammation. In order to increase sensitivity for joint inflammation, the historical clinical approach of considering doubtful swelling the absence of swelling should be revisited to interpret clinical doubtfulness as an indication of swelling.

12.
Nat Rev Rheumatol ; 16(10): 545-546, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32690928
14.
Ann Rheum Dis ; 79(7): 874-882, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32371387

RESUMO

BACKGROUND: Rheumatoid arthritis (RA) is characterised by clinical joint swelling and elevation of acute phase reactant levels, typically measured by the C-reactive protein (CRP). Clinical and inflammatory responses are usually concordant, except for inhibition of IL-6, which often disproportionally reduces the CRP due to direct inhibition of its hepatic production. We investigated whether pre-treatment CRP is a useful marker that can guide a preferential treatment choice towards IL-6 inhibition. METHODS: Data of 1126 treatment courses with tocilizumab (TCZ; early RA), 250 courses of rituximab (RTX; established RA) and 249 courses of methotrexate (MTX; established RA) were analysed. We compared clinical disease activity index (CDAI) values and change along 24 weeks' follow-up to CRP values at baseline or its early change. We validated the results using data from a separate TCZ trial in early RA. RESULTS: CRP levels in the TCZ group on average dropped by 74% within 4 weeks. Patients who attained CDAI remission at 24 weeks on TCZ had the highest baseline CRP levels while patients in high disease activity had the lowest; this association was reverse in the RTX and MTX groups. TCZ patients who achieved remission at 24 weeks showed the largest reductions of CRP levels by week 4 compared with those reaching higher disease activity states. Early CRP non-response was indicative of a risk of not achieving clinical treatment goals (p=0.038). CONCLUSION: Baseline CRP appears to have a positive association with reaching the therapeutic target on TCZ treatment, but is a negative predictor for RTX and MTX. Patients on TCZ without an early CRP response have a lower chance of achieving remission. CRP and its early course may inform, to some extent, the estimation of potential therapeutic success in patients with RA.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/sangue , Artrite Reumatoide/tratamento farmacológico , Proteína C-Reativa/análise , Adulto , Idoso , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
15.
PLoS One ; 15(5): e0233781, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32459816

RESUMO

OBJECTIVE: Cases of inflammatory bowel disease (IBD) during treatment with interleukin (IL)-17 antagonists have been reported from trials in psoriasis, psoriatic arthritis, and ankylosing spondylitis. The aim of this study was to assess the overall risk for development of IBD due to IL-17 inhibition. DESIGN: Systematic review and meta-analysis of studies conducted 2010-2018 of treatment with IL-17 antagonists in patients with psoriasis, psoriatic arthritis, ankylosing spondylitis, and rheumatoid arthritis. We compared risk of IBD development in anti-IL-17 treated patients compared to placebo treatments. We also computed incident rates of IBD overall. A 'worst case scenario' defining subjects ambiguous for prevalent versus incident cases for the latter was also applied. RESULTS: Sixty-six studies of 14,390 patients exposed to induction and 19,380 patients exposed to induction and/or maintenance treatment were included. During induction, 11 incident cases of IBD were reported, whereas 33 cases were diagnosed during the entire treatment period. There was no difference in the pooled risk of new-onset IBD during induction studies for both the best-case [risk difference (RD) 0.0001 (95% CI: -0.0011, 0.0013)] and worst-case scenario [RD 0.0008 (95% CI: -0.0005, 0.0022)]. The risk of IBD was not different from placebo when including data from maintenance and long-term extension studies [RD 0.0007 (95% CI: -0.0023, 0.0036) and RD 0.0022 (95% CI: -0.0010, 0.0055), respectively]. CONCLUSIONS: The risk for development of IBD in patients treated with IL-17 antagonists is not elevated. Prospective surveillance of patients treated with IL-17 antagonists with symptom and biomarker assessments is warranted to assess for onset of IBD in these patients.


Assuntos
Anticorpos Monoclonais , Artrite Psoriásica , Artrite Reumatoide , Doenças Inflamatórias Intestinais , Interleucina-17/antagonistas & inibidores , Espondilite Anquilosante , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Artrite Psoriásica/epidemiologia , Artrite Psoriásica/imunologia , Artrite Psoriásica/patologia , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/imunologia , Artrite Reumatoide/patologia , Feminino , Humanos , Doenças Inflamatórias Intestinais/induzido quimicamente , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/imunologia , Interleucina-17/imunologia , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Espondilite Anquilosante/tratamento farmacológico , Espondilite Anquilosante/epidemiologia , Espondilite Anquilosante/imunologia , Espondilite Anquilosante/patologia
17.
Ann Rheum Dis ; 79(6): 700-712, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32434812

RESUMO

OBJECTIVE: To update the European League Against Rheumatism (EULAR) recommendations for the pharmacological treatment of psoriatic arthritis (PsA). METHODS: According to the EULAR standardised operating procedures, a systematic literature review was followed by a consensus meeting to develop this update involving 28 international taskforce members in May 2019. Levels of evidence and strengths of recommendations were determined. RESULTS: The updated recommendations comprise 6 overarching principles and 12 recommendations. The overarching principles address the nature of PsA and diversity of both musculoskeletal and non-musculoskeletal manifestations; the need for collaborative management and shared decision-making is highlighted. The recommendations provide a treatment strategy for pharmacological therapies. Non-steroidal anti-inflammatory drugs and local glucocorticoid injections are proposed as initial therapy; for patients with arthritis and poor prognostic factors, such as polyarthritis or monoarthritis/oligoarthritis accompanied by factors such as dactylitis or joint damage, rapid initiation of conventional synthetic disease-modifying antirheumatic drugs is recommended. If the treatment target is not achieved with this strategy, a biological disease-modifying antirheumatic drugs (bDMARDs) targeting tumour necrosis factor (TNF), interleukin (IL)-17A or IL-12/23 should be initiated, taking into account skin involvement if relevant. If axial disease predominates, a TNF inhibitor or IL-17A inhibitor should be started as first-line disease-modifying antirheumatic drug. Use of Janus kinase inhibitors is addressed primarily after bDMARD failure. Phosphodiesterase-4 inhibition is proposed for patients in whom these other drugs are inappropriate, generally in the context of mild disease. Drug switches and tapering in sustained remission are addressed. CONCLUSION: These recommendations provide stakeholders with an updated consensus on the pharmacological management of PsA, based on a combination of evidence and expert opinion.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Glucocorticoides/uso terapêutico , Sociedades Médicas , Consenso , Conferências de Consenso como Assunto , Tomada de Decisão Compartilhada , Europa (Continente) , Humanos , Interleucina-12/antagonistas & inibidores , Interleucina-17/antagonistas & inibidores , Interleucina-23/antagonistas & inibidores , Inibidores de Janus Quinases/uso terapêutico , Inibidores da Fosfodiesterase 4/uso terapêutico , Medicamentos Sintéticos/uso terapêutico , Revisões Sistemáticas como Assunto , Fator de Necrose Tumoral alfa/antagonistas & inibidores
19.
Nat Med ; 26(6): 974-980, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32313250

RESUMO

Phase 3 trials are the mainstay of drug development across medicine but have often not met expectations set by preceding phase 2 studies. A systematic meta-analysis evaluated all randomized controlled, double-blind trials investigating targeted disease-modifying anti-rheumatic drugs in rheumatoid and psoriatic arthritis. Primary outcomes of American College of Rheumatology (ACR) 20 responses were compared by mixed-model logistic regression, including exploration of potential determinants of efficacy overestimation. In rheumatoid arthritis, phase 2 trial outcomes systematically overestimated subsequent phase 3 results (odds ratio comparing ACR20 in phase 2 versus phase 3: 1.39, 95% confidence interval: 1.25-1.57, P < 0.001). Data for psoriatic arthritis trials were similar, but not statistically significant (odds ratio comparing ACR20 in phase 2 versus phase 3: 1.35, 95% confidence interval: 0.94-1.94, P = 0.09). Differences in inclusion criteria largely explained the observed differences in efficacy findings. Our findings have implications for all stakeholders in new therapeutic development and testing, as well as potential ethical implications.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Desenvolvimento de Medicamentos , Humanos , Modelos Logísticos , Avaliação de Resultados em Cuidados de Saúde , Resultado do Tratamento
20.
J Autoimmun ; 110: 102405, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32276742

RESUMO

Precision medicine (PM) is a very commonly used term that implies a highly individualized and tailored approach to patient management. There are, however, many layers of precision, as for example taking an appropriate patient history, or performing additional lab or imaging tests are already helping to better tailor treatments to the right patient. All this adds to the narrower definition of PM, which implies using the unique molecular characteristics of a patient for management decisions. Big data has become an essential part of PM, including as much information as possible to improve precision of disease management, although integration of multi-source data continues to be a challenge in practical application. In research big data can identify new (sub-)phenotypes in unsupervised analyses, which ultimately advance precision by allowing new targeted therapeutic approaches. We will discuss the current status of PM in rheumatoid arthritis (RA) in the management areas of diagnosis, prognosis, selection of therapy, and decision to reduce therapy. PM markers for diagnosis of RA are usually markers of RA classification rather than diagnosis, and subtypes of RA are potentially underrecognized. Prognostic precision is well established for RA, including markers of disease activity or structure, as well as autoantibodies and genetics. The choice of the right compound in a patient identified to have a poor prognosis, however, remains widely arbitrary. Finally and most recently, the most reliable markers for a safe withdrawal of therapy continue to be lower levels of disease activity and longer presence of remission.

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