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1.
Ann Rheum Dis ; 82(2): 169-174, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36202589

RESUMEN

Systemic lupus erythematosus (SLE) is an autoimmune rheumatic disease of unknown aetiology, characterised by the production of auto-antibodies and formation of immune complexes against self-antigens and complement activation. This inflammatory response can lead to tissue infiltration and eventually, to organ damage.Patients with SLE invariably have periods of relapse and remission. Flares can occur even when the patient is on seemingly adequate treatment, which suggests that more effective therapies are necessary for the management of SLE. Thus, trials with many drugs against different targets, such as CD22, IL-12 and IL-23 or tyrosine kinases, have been carried out in recent years.A frustrating feature of some of the biologic drugs used to treat SLE has been the reporting of successful phase II trials followed by failures of the phase III trials.In this review, we will focus on phase II and III trials carried out with epratuzumab (anti CD22), baricitinib (Janus kinases inhibitor), rigerimod (P140 peptide) and ustekinumab (IL-12 and IL-23 inhibitor) and consider the reasons for their ultimate failure to 'make the grade'. Likewise, we will try to explain the possible reasons that can influence why good results may be obtained in phase II trials and lead to undue optimism.


Asunto(s)
Lupus Eritematoso Sistémico , Humanos , Lupus Eritematoso Sistémico/tratamiento farmacológico , Interleucina-12 , Ustekinumab/uso terapéutico , Transducción de Señal , Interleucina-23 , Ensayos Clínicos Fase III como Asunto , Ensayos Clínicos Fase II como Asunto
2.
Ann Rheum Dis ; 82(9): 1123-1129, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37336639

RESUMEN

In recent years, treat-to-target strategy and early intervention strategies with immunosuppressive agents have attempted to improve the prognosis and outcome in patients with autoimmune inflammatory rheumatic diseases. However, infectious complications due to side effects of medication remain a major concern in routine practice. In this regard, vaccine immunity and vaccination programmes are of the utmost importance in patients with systemic lupus erythematosus (SLE) in terms of morbidity and mortality. Encouragingly, research investigations have increased exponentially, both in monitoring the vaccines efficacy, and in determining the immune response while patients are on immunosuppression., However, in this biological era in rheumatology, relatively little data have been published investigating these parameters in those receiving biological agents, therefore, no definitive consensus about a vaccination policy for patients with SLE is currently available. In this review, we aim to address what is established about vaccinating patients with SLE on biological agents and discuss potential problems.

3.
Ann Rheum Dis ; 82(7): 927-936, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37085289

RESUMEN

OBJECTIVES: A novel longitudinal clustering technique was applied to comprehensive autoantibody data from a large, well-characterised, multinational inception systemic lupus erythematosus (SLE) cohort to determine profiles predictive of clinical outcomes. METHODS: Demographic, clinical and serological data from 805 patients with SLE obtained within 15 months of diagnosis and at 3-year and 5-year follow-up were included. For each visit, sera were assessed for 29 antinuclear antibodies (ANA) immunofluorescence patterns and 20 autoantibodies. K-means clustering on principal component analysis-transformed longitudinal autoantibody profiles identified discrete phenotypic clusters. One-way analysis of variance compared cluster enrolment demographics and clinical outcomes at 10-year follow-up. Cox proportional hazards model estimated the HR for survival adjusting for age of disease onset. RESULTS: Cluster 1 (n=137, high frequency of anti-Smith, anti-U1RNP, AC-5 (large nuclear speckled pattern) and high ANA titres) had the highest cumulative disease activity and immunosuppressants/biologics use at year 10. Cluster 2 (n=376, low anti-double stranded DNA (dsDNA) and ANA titres) had the lowest disease activity, frequency of lupus nephritis and immunosuppressants/biologics use. Cluster 3 (n=80, highest frequency of all five antiphospholipid antibodies) had the highest frequency of seizures and hypocomplementaemia. Cluster 4 (n=212) also had high disease activity and was characterised by multiple autoantibody reactivity including to antihistone, anti-dsDNA, antiribosomal P, anti-Sjögren syndrome antigen A or Ro60, anti-Sjögren syndrome antigen B or La, anti-Ro52/Tripartite Motif Protein 21, antiproliferating cell nuclear antigen and anticentromere B). Clusters 1 (adjusted HR 2.60 (95% CI 1.12 to 6.05), p=0.03) and 3 (adjusted HR 2.87 (95% CI 1.22 to 6.74), p=0.02) had lower survival compared with cluster 2. CONCLUSION: Four discrete SLE patient longitudinal autoantibody clusters were predictive of long-term disease activity, organ involvement, treatment requirements and mortality risk.


Asunto(s)
Autoanticuerpos , Lupus Eritematoso Sistémico , Humanos , Anticuerpos Antinucleares , ADN , Inmunosupresores , Aprendizaje Automático
4.
Ann Rheum Dis ; 81(11): 1541-1548, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35944946

RESUMEN

OBJECTIVE: To determine the independent impact of different definitions of remission and low disease activity (LDA) on damage accrual. METHODS: Patients with ≥2 annual assessments from a longitudinal multinational inception lupus cohort were studied. Five mutually exclusive disease activity states were defined: remission off-treatment: clinical Systemic Lupus Erythematosus Disease Activity Index (cSLEDAI)-2K=0, without prednisone or immunosuppressants; remission on-treatment: cSLEDAI-2K score=0, prednisone ≤5 mg/day and/or maintenance immunosuppressants; low disease activity Toronto cohort (LDA-TC): cSLEDAI-2K score of ≤2, without prednisone or immunosuppressants; modified lupus low disease activity (mLLDAS): Systemic Lupus Erythematosus Disease Activity Index-2K score of 4 with no activity in major organ/systems, no new disease activity, prednisone ≤7.5 mg/day and/or maintenance immunosuppressants; active: all remaining visits. Only the most stringent definition was used per visit. Antimalarials were allowed in all. The proportion of time that patients were in a specific state at each visit since cohort entry was determined. Damage accrual was ascertained with the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Univariable and multivariable generalised estimated equation negative binomial regression models were used. Time-dependent covariates were determined at the same annual visit as the disease activity state but the SDI at the subsequent visit. RESULTS: There were 1652 patients, 1464 (88.6%) female, mean age at diagnosis 34.2 (SD 13.4) years and mean follow-up time of 7.7 (SD 4.8) years. Being in remission off-treatment, remission on-treatment, LDA-TC and mLLDAS (per 25% increase) were each associated with a lower probability of damage accrual (remission off-treatment: incidence rate ratio (IRR)=0.75, 95% CI 0.70 to 0.81; remission on-treatment: IRR=0.68, 95% CI 0.62 to 0.75; LDA: IRR=0.79, 95% CI 0.68 to 0.92; and mLLDAS: IRR=0.76, 95% CI 0.65 to 0.89)). CONCLUSIONS: Remission on-treatment and off-treatment, LDA-TC and mLLDAS were associated with less damage accrual, even adjusting for possible confounders and effect modifiers.


Asunto(s)
Antimaláricos , Lupus Eritematoso Sistémico , Antimaláricos/uso terapéutico , Progresión de la Enfermedad , Femenino , Humanos , Inmunosupresores/uso terapéutico , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Masculino , Prednisona/uso terapéutico , Inducción de Remisión , Índice de Severidad de la Enfermedad
6.
Health Qual Life Outcomes ; 14: 33, 2016 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-26927364

RESUMEN

BACKGROUND: An in-depth qualitative exploration of uncertainty in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) led to the development of a five-domain conceptual framework of patient uncertainty in these two conditions. The purpose of this study was to develop and evaluate a new patient-reported outcome (PRO) instrument for patient uncertainty in SLE and RA on the basis of this empirically developed conceptual framework. METHODS: Cognitive debriefing interviews were conducted to pre-test the initial items generated on the basis of the preliminary qualitative exploration of patient uncertainty in SLE and RA. Two separate field tests were conducted in five hospital sites to evaluate the measurement properties of the new instrument; the first to identify and form scales, and the second to assess measurement properties of the final version in an independent sample. Psychometric evaluation was conducted in line with the Rasch Measurement Theory (RMT), examining the extent to which sample to scale targeting was satisfactory, measurement scales were constructed effectively and the sample was measured successfully. Traditional psychometric techniques were also used to provide complementary analyses best understood by clinicians. RESULTS: Pre-testing supported the relevance, acceptability and comprehensibility of the initial items. Findings indicated that the Patient Uncertainty Questionnaire for Rheumatology PUQ-R instrument fulfilled the expectations of RMT to a large extent (including person separation index 0.73 - 0.91). The PUQ-R comprises 49 items across five scales; symptoms and flares (14 items), medication (11 items), trust in doctor (8 items), self-management (6 items) and impact (10 items) which further displayed excellent measurement properties as assessed against the traditional psychometric criteria (including Cronbach's alpha 0.82 - 0.93). CONCLUSION: The PUQ-R has been developed and evaluated specifically for patients with SLE and RA. By quantifying uncertainty, the PUQ-R has the potential to support evidence-based management programmes and research.


Asunto(s)
Artritis Reumatoide/psicología , Lupus Eritematoso Sistémico/psicología , Evaluación del Resultado de la Atención al Paciente , Psicometría/instrumentación , Calidad de Vida/psicología , Incertidumbre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Inglaterra , Femenino , Humanos , Masculino , Persona de Mediana Edad , Autoinforme , Encuestas y Cuestionarios , Adulto Joven
7.
J Clin Med ; 12(9)2023 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-37176637

RESUMEN

For many years, the failure of randomized controlled trials (RCTs) has prevented patients with systemic lupus erythematosus (SLE) from benefiting from biological drugs that have proved to be effective in other rheumatological diseases. Only two biologics are approved for SLE, however they can only be administered to a restricted proportion of patients. Recently, several phase II RCTs have evaluated the efficacy and safety of new biologics in extra-renal SLE and lupus nephritis. Six drug trials have reported encouraging results, with an improvement in multiple clinical and serological outcome measures. The possibility of combining B-cell depletion and anti-BLyS treatment has also been successfully explored.

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