Differences in rituximab use between pediatric rheumatologists and nephrologists for the treatment of refractory lupus nephritis and renal flare in childhood-onset SLE.

BACKGROUND: Consensus treatment plans have been developed for induction therapy of newly diagnosed proliferative lupus nephritis (LN) in childhood-onset systemic lupus erythematosus. However, patients who do not respond to initial therapy, or who develop renal flare after remission, warrant escalation of treatment. Our objective was to assess current practices of pediatric nephrologists and rheumatologists in North America in treatment of refractory proliferative LN and flare. METHODS: Members of Childhood Arthritis and Rheumatology Research Alliance (CARRA) and the American Society for Pediatric Nephrology (ASPN) were surveyed in November 2015 to assess therapy choices (other than modifying steroid dosing) and level of agreement between rheumatologists and nephrologists for proliferative LN patients. Two cases were presented: (1) refractory disease after induction treatment with corticosteroid and cyclophosphamide (CYC) and (2) nephritis flare after initial response to treatment. Survey respondents chose treatments for three follow up scenarios for each case that varied by severity of presentation. Treatment options included CYC, mycophenolate mofetil (MMF), rituximab (RTX), and others, alone or in combination. RESULTS: Seventy-six respondents from ASPN and foty-one respondents from CARRA represented approximately 15 % of the eligible members from each organization. Treatment choices between nephrologists and rheumatologists were highly variable and received greater than 50 % agreement for an individual treatment choice in only the following 2 of 6 follow up scenarios: 59 % of nephrologists, but only 38 % of rheumatologists, chose increasing dose of MMF in the case of LN refractory to induction therapy with proteinuria, hematuria, and improved serum creatinine. In a follow up scenario showing severe renal flare after achieving remission with induction therapy, 58 % of rheumatologists chose CYC and RTX combination therapy, whereas the top choice for nephrologists (43 %) was CYC alone. Rheumatologists in comparison to nephrologists chose more therapy options that contained RTX in all follow up scenarios except one (p < 0.05). CONCLUSIONS: Therapy choices for pediatric rheumatologists and nephrologists in the treatment of refractory LN or LN flare were highly variable with rheumatologists more often choosing rituximab. Further investigation is necessary to delineate the reasons behind this finding. This study highlights the importance of collaborative efforts in developing consensus treatment plans for pediatric LN.

Clinical remission and subsequent relapse in patients with juvenile idiopathic arthritis: predictive factors according to therapeutic approach.

BACKGROUND: Juvenile idiopathic arthritis constitutes a significant cause of disability and quality of life impairment in pediatric and adult patients. The aim of this study was to ascertain clinical remission (CR) and subsequent relapse in juvenile idiopathic arthritis (JIA) patients, according to therapeutic approach and JIA subtype. Evidence in literature regarding its predictors is scarce. METHODS: We conducted an observational, ambispective study. Patients diagnosed of JIA, treated with synthetic and/or biologic disease modifying antirheumatic drugs (DMARD) were included and followed-up to December 31st, 2015. Primary outcome was clinical remission defined by Wallace criteria, both on and off medication. In order to ascertain CR according to therapeutic approach, DMARD treatments were divided in four groups: 1) synthetic DMARD (sDMARD) alone, 2) sDMARD combined with another sDMARD, 3) sDMARD combined with biologic DMARD (bDMARD), and 4) bDMARD alone. RESULTS: A total of 206 patients who received DMARD treatment were included. At the time the follow-up was completed, 70% of the patients in the cohort had attained CR at least once (144 out of 206), and 29% were in clinical remission off medication (59 out of 206). According to treatment group, CR was more frequently observed in patients treated with synthetic DMARD alone (53%). Within this group, CR was associated with female sex, oligoarticular persistent subtypes, ANA positivity, Methotrexate treatment and absence of HLA B27, comorbidities and DMARD toxicity. 124 DMARD treatments (62%) were withdrawn, 64% of which relapsed. Lower relapse rates were observed in those patients with persistent oligoarticular JIA (93%) when DMARD dose was tapered before withdrawal (77%). CONCLUSIONS: More than two thirds of JIA patients attained CR along the 9 years of follow-up, and nearly one third achieved CR off medication. Females with early JIA onset, lower active joint count and ANA positivity were the ones achieving and sustaining remission more frequently, especially when receiving synthetic DMARD alone and in the absence of HLA B27, comorbidities or previous DMARD toxicity.

Juvenile idiopathic arthritis: from aetiopathogenesis to therapeutic approaches.

Juvenile idiopathic arthritis (JIA) is the most common paediatric rheumatological disorder and is classified by subtype according to International League of Associations for Rheumatology criteria. Depending on the number of joints affected, presence of extra-articular manifestations, systemic symptoms, serology and genetic factors, JIA is divided into oligoarticular, polyarticular, systemic, psoriatic, enthesitis-related and undifferentiated arthritis. This review provides an overview of advances in understanding of JIA pathogenesis focusing on aetiology, histopathology, immunological changes associated with disease activity, and best treatment options. Greater understanding of JIA as a collective of complex inflammatory diseases is discussed within the context of therapeutic interventions, including traditional non-biologic and up-to-date biologic disease-modifying anti-rheumatic drugs. Whilst the advent of advanced therapeutics has improved clinical outcomes, a considerable number of patients remain unresponsive to treatment, emphasising the need for further understanding of disease progression and remission to support stratification of patients to treatment pathways.

Disseminated coccidioidomycosis in a patient with juvenile idiopathic arthritis receiving infliximab.

BACKGROUND: Coccidioides immitis is a dimorphic fungus endemic to the arid climates of the Southwest United States, Mexico and parts of Central and South America. Human infection occurs through inhalation of spores with less than half of exposures progressing to a symptomatic state that primarily consists of pulmonary manifestations. Disseminated coccidioidomycosis is exceedingly rare, occurring in fewer than 1 % of symptomatic infections. Through hematogenous spread, the fungus can infect most organ systems and may be fatal without systemic antifungal treatment. Individuals with impaired cell-mediated immunity either from primary immunodeficiency disorders or secondary to immunosuppression with medications such as tumor necrosis factor alpha (TNF-α) inhibitors have increased risk of disseminated coccidioidomycosis and previous cases of coccidioidomycosis have been reported with biologic therapy. CASE PRESENTATION: We present a case of disseminated coccidioidomycosis in a 16-year-old female with polyarticular juvenile idiopathic arthritis (JIA) being treated with prednisone, methotrexate, and infliximab. The patient presented with symptoms of meningeal irritation, bilateral choroidal lesions, and necrotizing peripheral pneumonia. Her infection was thought to be a reactivation of coccidioidomycosis given her history of resolved pneumonia that occurred after traveling to Arizona, New Mexico, and El Paso one year prior to presentation. Following diagnosis, she improved with discontinuation of her immunosuppressive medications and two weeks of intravenous amphotericin B and fluconazole with plans for lifetime treatment with fluconazole while immunosuppressed. Due to worsening arthritis, she will begin tofacitinib and continue close monitoring of chest x-rays and coccidioides antibody. CONCLUSIONS: Patients undergoing immunosuppressive therapy for rheumatological conditions are at increased risk of disseminated coccidioidomycosis and should be evaluated with high suspicion when presenting with atypical symptoms and history of travel to endemic regions.

Findings and feasibility of major salivary gland ultrasound in childhood-onset systemic lupus erythematosus: a pilot study.

BACKGROUND: Childhood-onset systemic lupus erythematosus (cSLE) is a complex autoimmune disorder with multi-organ manifestations and can be associated with other rheumatic diseases including Sjögren's syndrome (SS). Salivary gland ultrasound (SGUS) represents a noninvasive tool to screen for salivary gland disease in rheumatic disease patients. The aims of this cross-sectional study were to determine feasibility of major SGUS in a clinic setting and to identify characteristics in a cohort of cSLE patients (without confirmed SS) that may be associated with salivary gland abnormalities consistent with secondary SS. METHODS: Patients with SLE onset prior to age 18 were recruited. Patients completed questionnaires rating symptoms and underwent major SGUS examination. Disease and demographic differences were compared between cSLE patients with abnormal SGUS vs. cSLE patients with normal SGUS using t-tests and Fisher's exact tests. RESULTS: Thirty-one cSLE patients were recruited, 84% were female, 55% were Caucasian. The average disease duration among all patients was 5 years. Average time to complete the SGUS examination and scoring protocol was 7 min. 35% of SGUS scores were abnormal and significantly associated with IgG level at diagnosis, and anti-Ro and anti-La antibodies. CONCLUSIONS: This is one of the first studies to our knowledge that assesses major SGUS in a cohort of patients with cSLE without prior diagnoses of SS. The SGUS protocol was feasible to perform by rheumatologists in a clinic setting. Although the sample size was small, SGUS abnormalities were identified in one-third of patients. IgG level at diagnosis and anti-Ro and anti-La antibodies may be associated with SGUS abnormalities.

The impact of seropositivity on the effectiveness of biologic anti-rheumatic agents: results from a collaboration of 16 registries.

OBJECTIVES: RF and ACPA are used as diagnostic tools and their presence has been associated with clinical response to some biologic DMARDs (bDMARDs) in RA. This study compared the impact of seropositivity on drug discontinuation and effectiveness of bDMARDs in patients with RA, using head-to-head comparisons in a real-world setting. METHODS: We conducted a pooled analysis of 16 observational RA registries. Inclusion criteria were a diagnosis of RA, initiation of treatment with rituximab (RTX), abatacept (ABA), tocilizumab (TCZ) or TNF inhibitors (TNFis) and available information on RF and/or ACPA status. Drug discontinuation was analysed using Cox regression, including drug, seropositivity, their interaction, adjusting for concomitant and past treatments and patient and disease characteristics and accounting for country and calendar year of bDMARD initiation. Effectiveness was analysed using the Clinical Disease Activity Index evolution over time. RESULTS: Among the 27 583 eligible patients, the association of seropositivity with drug discontinuation differed across bDMARDs (P for interaction <0.001). The adjusted hazard ratios for seropositive compared with seronegative patients were 1.01 (95% CI 0.95, 1.07) for TNFis, 0.89 (0.78, 1.02)] for TCZ, 0.80 (0.72, 0.88) for ABA and 0.70 (0.59, 0.84) for RTX. Adjusted differences in remission and low disease activity rates between seropositive and seronegative patients followed the same pattern, with no difference in TNFis, a small difference in TCZ, a larger difference in ABA and the largest difference in RTX (Lundex remission difference +5.9%, low disease activity difference +11.6%). CONCLUSION: Seropositivity was associated with increased effectiveness of non-TNFi bDMARDs, especially RTX and ABA, but not TNFis.

Biological dose tapering in daily clinical practice: a 10 year follow-up study / Optimización de la dosis de biológicos en práctica clínica: experiencia de 10 años

OBJECTIVE: To describe practice patterns, long-term outcome, and related factors, in relation to biological therapies tapering in rheumatoid arthritis (RA) patients in a well-controlled real-world setting. METHODS: An observational longitudinal retrospective 10-year study was conducted in all RA patients receiving biological agents in an RA clinic from May 2003 to October 2013. Biological treatment of patients with sustained DAS28<3.2 or SDAI<11 was tapered (dose down-titrated or interval widen) or discontinued as per practice protocol. Primary outcome of tapering was relapse, defined as an increase in DAS28≥1.2. Descriptive, survival analysis, and logistic regression analysis with first relapse as dependent variable were carried out. RESULTS: Of 193 RA patients on biological treatment (mean age 54±14 years, 81% women), tapering was applied in 106 (55%) and discontinuation in 34 (17.6%). During follow-up 38 patients relapsed (62%). Rate of relapse was 10% at 6 months, 19% at 12 months, 33.2% at 2 years and 50% after 5 years. Mean time in dose reduction was 4.5 years [95% confidence interval (95% CI): 3.7-5.3]. Six patients (15.7%) did not respond after reinstatement of full dose of biologic. In the multivariate analysis, pain [OR=1.26 (95% CI: 1.11-1.43); P<.001] and erythrocyte sedimentation rate (ESR) [OR=1.01 (95% CI: 1.00-1.03); P=.011] at baseline were associated with relapse after tapering. CONCLUSIONS: Tapering may be considered a long-term option in RA patients on biologics and low disease activity, especially if low ESR and pain scores are present at baseline; treatment reinstatement could be considered a safe option in case of relapse

OBJETIVO: Describir los patrones de práctica clínica, los resultados a largo plazo y los factores relacionados en relación a la optimización de las terapias biológicas en pacientes con artritis reumatoide (AR) en un entorno de vida real bien controlado. MÉTODOS: Se realizó un estudio retrospectivo observacional longitudinal de 10 años que incluyó a todos los pacientes con AR que recibieron agentes biológicos en una consulta monográfica de AR entre mayo de 2003 y octubre de 2013. Se optimizó el tratamiento biológico (ajuste de dosis o ampliación de intervalo) en los pacientes con DAS28<3,2 o SDAI<11 de forma mantenida según un protocolo de práctica clínica. La variable principal fue la recaída, definida como un aumento en el DAS28≥1,2. Se realizó un análisis descriptivo, de supervivencia y modelos de regresión logística con la primera recaída como variable dependiente. RESULTADOS: De 193 pacientes con AR en tratamiento biológico (edad media 54±14 años, 81% mujeres), se optimizó la dosis en 106 (55%) y se interrumpió el tratamiento en 34 (17,6%). Durante el seguimiento 38 pacientes recayeron (62%). La tasa de recaída fue del 10% a los 6 meses, del 19% a los 12 meses, del 33,2% a los 2 años y del 50% a los 5 años. El tiempo medio con dosis reducida fue de 4 años y medio (intervalo de confianza del 95% [IC 95%]: 3,7 a 5,3). Seis pacientes (15,7%) no respondieron después de restablecer la dosis completa de biológico. En el análisis multivariado, el dolor (OR=1,26 [IC 95%: 1,11 a 1,43]; p < 0,001) y la velocidad de sedimentación globular (VSG) (OR por mm/h=1,01 [IC 95%: 1,00 a 1,03]; p = 0,011) al inicio del estudio se asociaron a recaída tras la optimización. CONCLUSIONES: La optimización de la dosis se puede considerar una opción a largo plazo en pacientes con AR en tratamiento con agentes biológicos y baja actividad de la enfermedad, especialmente si la VSG y el dolor están en niveles bajos; la reinstauración del tratamiento podría considerarse una opción segura en caso de recaída en la mayoría de los pacientes

Incidence and clinical course of COVID-19 in patients with rheumatologic diseases: A population-based study.

OBJECTIVES: Patients with rheumatologic diseases might be more susceptible to COVID-19 and carry a poorer prognosis. The aim of this study is to examine the incidence and outcomes of all COVID-19 patients with rheumatologic conditions in Hong Kong. METHODS: This is a population-based retrospective study. All patients tested positive for SARS-CoV-2 by PCR with a previous diagnosis of rheumatologic diseases were reviewed. The incidence of COVID-19 in patients with rheumatologic conditions was calculated and compared to the general population in Hong Kong. Descriptive data of those rheumatologic patients with COVID-19 and the clinical course of the index infection were presented. RESULTS: Up till 27 May 2020, there were 1067 cases of COVID-19 diagnosed in Hong Kong which had a population of 7.5 million. Out of the 39,835 patients with underlying rheumatologic diseases, we identified 5 PCR confirmed COVID-19 cases. The estimated incidence of COVID-19 was 0.0126% patients with rheumatologic diseases, compared to 0.0142% in the general population. All 5 patients had inflammatory arthropathies. One patient was on hydroxychloroquine and sulphasalazine, and one was on methotrexate. None of the 3534 patients on b/tsDMARDs was infected. Four patients had leucopenia/lymphopenia and stool viral PCR was positive in 3 patients. All patients made uneventful recovery without complications or flare of underlying diseases. CONCLUSIONS: We found no alarming signals of increased frequency or severity of COVID-19 in patients with rheumatologic diseases, although extrapolation of the results to other populations with different infection control strategies should be made with caution.

Cytokine storm in COVID-19: pathogenesis and overview of anti-inflammatory agents used in treatment.

COVID-19 infection has a heterogenous disease course; it may be asymptomatic or causes only mild symptoms in the majority of the cases, while immunologic complications such as macrophage activation syndrome also known as secondary hemophagocytic lymphohistiocytosis, resulting in cytokine storm syndrome and acute respiratory distress syndrome, may also occur in some patients. According to current literature, impairment of SARS-CoV-2 clearance due to genetic and viral features, lower levels of interferons, increased neutrophil extracellular traps, and increased pyroptosis and probable other unknown mechanisms create a background for severe disease course complicated by macrophage activation syndrome and cytokine storm. Various genetic mutations may also constitute a risk factor for severe disease course and occurrence of cytokine storm in COVID-19. Once, immunologic complications like cytokine storm occur, anti-viral treatment alone is not enough and should be combined with appropriate anti-inflammatory treatment. Anti-rheumatic drugs, which are tried for managing immunologic complications of COVID-19 infection, will also be discussed including chloroquine, hydroxychloroquine, JAK inhibitors, IL-6 inhibitors, IL-1 inhibitors, anti-TNF-α agents, corticosteroids, intravenous immunoglobulin (IVIG), and colchicine. Early recognition and appropriate treatment of immunologic complications will decrease the morbidity and mortality in COVID-19 infection, which requires the collaboration of infectious disease, lung, and intensive care unit specialists with other experts such as immunologists, rheumatologists, and hematologists.

COVID-19 in rheumatic disease patients on immunosuppressive agents.

OBJECTIVE: To analyze clinical characteristics and outcome of COVID-19 patients with underlying rheumatic diseases (RD) on immunosuppressive agents. METHOD: A case series of COVID-19 patients with RD on disease modifying anti-rheumatic drugs (DMARDs) were studied by a retrospective chart review. A literature search identified 9 similar studies of single cases and case series, which were also included. RESULTS: There were 4 COVID-19 inpatients with RD from our hospital, and the mean age was 57 ± 21 years. Two patients had a mild infection, and 2 developed severe COVID-19 related respiratory complications, including 1 patient on secukinumab requiring mechanical ventilation and 1 patient on rituximab developing viral pneumonia requiring supplemental oxygenation. All 4 patients had elevated acute phase reactants, 2 patients had mild COVID-19 with lymphopenia, and 2 patients had severe COVID-19 with normal lymphocyte counts, and high levels of IL-6. None of the patients exhibited an exacerbation of their underlying RD. In the literature, there were 9 studies of COVID-19 involving 197 cases of various inflammatory RD. Most patients were on DMARDs or biologics, of which TNFα inhibitors were most frequently used. Two tocilizumab users had a mild infection. Two patients were on rituximab with 1 severe COVID-19 requiring mechanical ventilation. Six patients were on secukinumab with 1 hospitalization. Of the total 201 cases, 12 died, with an estimated mortality of 5.9% CONCLUSION: Patients with RD are susceptible to COVID-19. Various DMARDs or biologics may affect the viral disease course differently. Patients on hydroxychloroquine, TNFα antagonists or tocilizumab may have a mild viral illness. Rituximab or secukinumab could worsen the viral disease. Further study is warranted.

Treat to Target in Systemic Lupus Erythematosus.

The treat-to-target principle of controlling inflammatory disease activity by means of disease-modifying antirheumatic drugs or immunosuppressive drugs also pertains to systemic lupus erythematosus (SLE). However, in SLE, intensifying immunosuppression with higher-dose glucocorticoids may worsen outcomes. Therefore, all current recommendations favor better disease control while limiting daily glucocorticoid doses to a maximum of 5 or 7.5 mg of prednisolone daily. Hydroxychloroquine and other prophylactic measures are added, and antiphospholipid syndrome is treated with anticoagulation and not with immunosuppression, which makes the approach of treat to target slightly more complex, mirroring the complexity of the disease.

Does Triple Conventional Synthetic Disease-Modifying Antirheumatic Drug Therapy Improve upon Methotrexate as the Initial Treatment of Choice for a Rheumatoid Arthritis Patient?

Although many treatment options exist for the initial management of rheumatoid arthritis, there has long been discussion about whether initial treatment should be with methotrexate (MTX) as monotherapy or in combination with other conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Although studies initially showed additional benefit from combining MTX with other csDMARDs, this benefit disappears when glucocorticoids are added to MTX, a strategy recommended in current guidelines as a short-term bridging approach until MTX therapy exhibits its full efficacy. Also concomitant use of glucocorticoids, with MTX may not be inferior to combination therapy of MTX with TNF-inhibitors.

Predictors of sick leave and improved worker productivity after 52 weeks of intensive treatment in patients with early rheumatoid arthritis.

Objective: To identify predictors of sick leave and improved worker productivity in patients with early rheumatoid arthritis (RA) treated for 52 weeks with intensive combination strategies. Methods: Patients with early RA were included in the COmbinatietherapie Bij Reumatoïde Artritis (COBRA)-light trial and followed for 52 weeks. As the COBRA-light strategy proved to be non-inferior to the COBRA strategy, all patients were pooled. Predictors for sick leave and improved worker productivity were assessed through a 3 month time-lag multivariable logistic generalized estimating equations model. Results: At baseline, 97 patients had a paid job, 59 had no job, and for six patients the work status was unknown. During the trial, 13 patients stopped working (8%) and six started working (4%). Only sick leave in the past 3 months predicted sick leave. By excluding this variable, patient global assessment and actual hours of sick leave became predictors. Increased worker productivity was predicted by higher patient global assessment levels, Sharp van der Heijde score ≥ 1, actual hours on sick leave, and higher worker productivity in the past 3 months. Conclusion: Sick leave and improved worker productivity were mainly predicted by non-disease-specific variables. Both outcomes can be predicted on a 3 month basis, using the outcome over the past 3 months for the next 3 months. By applying this model in daily practice, decisions for therapy change could be based not solely on disease activity but also taking into account a possible high risk for sick leave in the upcoming 3 months.

Pharmacological management of axial spondyloarthritis in adults.

Introduction: Spondyloarthritis (SpA) refers to a group of disorders sharing common clinical, genetic and imaging characteristics. Axial (ax) SpA corresponds to a subgroup that mainly affects the axial skeleton, leading to inflammatory back pain and progressive radiographic changes of the sacroiliac joints and the spine. axSpA are currently subdivided into two forms, namely the radiographic and nonradiographic form, and are associated with musculoskeletal pain, restriction of spinal mobility, specific extra-articular features and overall, altered quality of life. The therapeutic management of axSpA has considerably progressed and is now well standardized. Areas covered: Herein, the author reviews the pharmacological treatments that may be used in axSpA, including radiographic and nonradiographic forms in addition to the role of nonsteroidal anti-inflammatory drugs (NSAIDs), TNF alpha (TNFi), and IL-17A (IL-17Ai) inhibitors. Expert opinion: NSAIDs remain the mainstay of initial therapy and biological agents may be then envisaged. TNFi and IL-17Ai may be used in axSpA, but physicians have more experience with TNFi. Only TNFi are licensed for the treatment of nonradiographic axSpA. IL-17Ai may be used as first or second line biologic disease modifying antirheumatic drugs (bDMARDs) and further results are needed to better define their position in the therapeutic management of axSpA.

Comparison of Adults With Polyarticular Juvenile Idiopathic Arthritis to Adults With Rheumatoid Arthritis: A Cross-sectional Analysis of Clinical Features and Medication Use.

BACKGROUND/OBJECTIVE: Many individuals with juvenile idiopathic arthritis (JIA) have persistent disease into adulthood. Polyarticular JIA (pJIA) is often mislabeled as rheumatoid arthritis (RA) in adult rheumatology clinics, and treatment for adult pJIA patients is not well defined. We aimed to describe clinical features and medication use in the adult pJIA population in relation to an RA control cohort. METHODS: We performed a cross-sectional study of 45 adults with pJIA and 94 with RA seen from 2013 to 2017. Clinical characteristics including RA classification criteria were compared using χ and McNemar tests. Medication use was analyzed focusing on tumor necrosis factor inhibitor (TNFi) survival, and an accelerated failure-time model was developed for time to methotrexate initiation. RESULTS: Polyarticular JIA patients were less likely to be rheumatoid factor or cyclic citrullinated peptide antibody positive; fewer than half of pJIA subjects met the RA 2010 American College of Rheumatology/European League Against Rheumatism Classification Criteria. Time from diagnosis to methotrexate initiation was associated with longer disease duration in both groups (p < 0.01). Current TNFi use was more prevalent in pJIA patients (49% vs. 18%, p < 0.01), and TNFi use, particularly for etanercept, was sustained longer with a median drug survival of 4.41 years compared with 0.70 years in RA patients (p < 0.01). CONCLUSIONS: Although often considered together in adult rheumatology practice, adults with pJIA are distinct from patients with RA. Medication use markedly differed between the 2 populations with greater prevalence and duration of TNFi use in pJIA patients. Further study is needed to improve outcomes in this unique population.

Tofacitinib 5 mg Twice Daily in Patients with Rheumatoid Arthritis and Inadequate Response to Disease-Modifying Antirheumatic Drugs: A Comprehensive Review of Phase 3 Efficacy and Safety.

BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We performed a comprehensive review of phase 3 studies of tofacitinib 5 mg twice daily (BID) (approved dose in many countries) in patients with moderate to severe RA and inadequate response to prior disease-modifying antirheumatic drugs. METHODS: A search of PubMed and ClinicalTrials.gov identified 5 studies: ORAL Solo (NCT00814307), ORAL Sync (NCT00856544), ORAL Standard (included adalimumab 40 mg once every 2 weeks; NCT00853385), ORAL Scan (NCT00847613), and ORAL Step (NCT00960440). Efficacy and safety data for tofacitinib 5 mg BID, placebo, and adalimumab were analyzed. RESULTS: Across the 5 studies, 1216 patients received tofacitinib 5 mg BID, 681 received placebo, and 204 received adalimumab. At month 3, tofacitinib demonstrated significantly higher 20%, 50%, and 70% improvement in American College of Rheumatology response criteria (ACR20, ACR50, and ACR70, respectively) response rates, greater improvement in Health Assessment Questionnaire-Disability Index, and a higher proportion of Disease Activity Score-defined remission than placebo. Frequencies of adverse events (AEs), serious AEs, and discontinuations due to AEs were similar for tofacitinib and placebo at month 3; serious infection events were more frequent for tofacitinib. In ORAL Standard, although not powered for formal comparisons, tofacitinib and adalimumab had numerically similar efficacy and AEs; serious AEs and serious infection events were more frequent with tofacitinib. CONCLUSIONS: Tofacitinib 5 mg BID reduced RA signs and symptoms and improved physical function versus placebo in patients with inadequate response to prior disease-modifying antirheumatic drugs. Tofacitinib 5 mg BID had a consistent, manageable safety profile across studies, with no new safety signals identified.

Anti-tumor necrosis factor biosimilars and intended copies in rheumatology: Perspective from the Asia Pacific region.

Although anti-tumor necrosis factor (TNF) agents have greatly improved the management of rheumatic diseases, their cost limits access to many patients throughout the world. As a result, patients and clinicians have turned to biosimilars to provide similar efficacy at a lower cost. Many of the regulatory guidelines in the Asia Pacific region are largely based on those of the European Medicines Agency and the World Health Organization; however, there are variations between countries. Additionally, in some countries, intended copies are available that were approved prior to the development of guidelines and have not fulfilled the requirements of a biosimilar. We review the various regulatory requirements for biosimilars in the Asia Pacific region, the anti-TNF biosimilars and intended copies approved in the region, and whether clinical data are available for these agents. We discuss concerns about the need for additional regulations and education, and we provide recommendations for a multidisciplinary pharmacovigilance approach that closely monitors the safety of biosimilar use.

Increased Prevalence of Metabolic Syndrome and Adipocytokine Levels in a Psoriatic Arthritis Cohort.

OBJECTIVE: The aims of this study were to evaluate the prevalence of metabolic syndrome (MetS) in psoriatic arthritis (PsA) patients according to the most recent definition in a Mediterranean population and to determine its association with biomarkers of inflammation and serum adipocytokine levels. METHODS: Demographic, clinical, and laboratory data were collected on 74 patients with PsA and 82 control subjects. The presence of MetS was determined according to the current "harmonization" definition. Serum adipocytokines were analyzed. Continuous variables were compared by t test and discrete variables by χ test. Multivariate regression models compared the association between the presence of MetS and the blood levels of adipocytokines. RESULTS: The prevalence of MetS was higher in PsA patients compared with the control group: 54.8% versus 36.6%, respectively (P = 0.02; odds ratio, 2.33; 95% confidence interval, 1.16-4.69). The main difference between the 2 groups was waist circumference. No association was found between MetS and parameters of articular and skin disease activity or treatment. Leptin levels and leptin/adiponectin ratio were higher in PsA patients compared with control subjects: 83.4 versus 51.7 ng/mL (P = 0.001) and 6.3 × 10 versus 4.1 × 10 (P = 0.015), respectively. There was no significant difference in the adiponectin levels between the groups. CONCLUSIONS: The prevalence of MetS was higher in PsA patients compared with non-PsA control subjects in this Mediterranean population. Clinicians caring for PsA patients ought to be aware of the increased risk of MetS in PsA patients, confirmed in different regions worldwide. The increased MetS seems to be linked to central obesity in these patients, and appropriate treatment recommendations are advised.

Rheumatoid Arthritis: Common Questions About Diagnosis and Management.

Rheumatoid arthritis is the most commonly diagnosed systemic inflammatory arthritis, with a lifetime prevalence of up to 1% worldwide. Women, smokers, and those with a family history of the disease are most often affected. Rheumatoid arthritis should be considered if there is at least one joint with definite swelling that is not better explained by another disease. In a patient with inflammatory arthritis, the presence of a rheumatoid factor and/or anti-citrullinated protein antibody, elevated C-reactive protein level, or elevated erythrocyte sedimentation rate is consistent with a diagnosis of rheumatoid arthritis. Rheumatoid arthritis may impact organs other than the joints, including lungs, skin, and eyes. Rapid diagnosis of rheumatoid arthritis allows for earlier treatment with disease-modifying antirheumatic drugs, which is associated with better outcomes. The goal of therapy is to initiate early medical treatment to achieve disease remission or the lowest disease activity possible. Methotrexate is typically the first-line agent for rheumatoid arthritis. Additional disease-modifying antirheumatic drugs or biologic agents should be added if disease activity persists. Comorbid conditions, including hepatitis B or C or tuberculosis infections, must be considered when choosing medical treatments. Although rheumatoid arthritis is often a chronic disease, some patients can taper and discontinue medications and remain in long-term remission.