Sergio Schwartzman

Validation of the Sapporo criteria for antiphospholipid syndrome.

OBJECTIVE To test the Sapporo criteria for the classification of the antiphospholipid syndrome (APS). METHODS We classified 243 consecutive patients who had clinical diagnoses of primary APS (n = 49), secondary APS (n = 26), systemic lupus erythematosus (SLE) without clinical APS (n = 131), and lupus-like disease without clinical APS (n = 37). RESULTS Sensitivity, specificity, positive predictive value, and negative predictive value were 0.71, 0.98, 0.95, and 0.88, respectively. False-negative findings were the result of patients being classified on the basis of minor criteria that were not included in the Sapporo criteria, such as livedo reticularis, thrombocytopenia, low-titer IgG or IgM anticardiolipin antibody, IgA anticardiolipin antibody, and anti-beta2-glycoprotein I antibody. Some patients with false-negative results were true seronegative cases. CONCLUSION The Sapporo criteria for APS compare favorably with the American College of Rheumatology criteria for SLE and are usable for clinical studies.

Group for Research and Assessment of Psoriasis and Psoriatic Arthritis 2015 Treatment Recommendations for Psoriatic Arthritis.

To update the 2009 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations for the spectrum of manifestations affecting patients with psoriatic arthritis (PsA).

Lymphoma in patients with rheumatoid arthritis : Association with the disease state or methotrexate treatment

Although long-term clinical studies have shown no excessive risk of lymphoma in rheumatoid arthritis (RA) patients treated with methotrexate (MTX), an increasing number of reports of this association continue to appear. We describe two cases, review the cases in the worlds literature, and summarize their important characteristics. Possible oncogenic mechanisms are discussed. Most lymphoproliferation cases presented here have features of immunosuppression-associated lymphoma. The immunosuppressed state is attributable to a combination of factors, such as RA itself and the actions of MTX. The risk factors for RA patients to develop lymphoma while on MTX include severe disease, intense immunosuppression, genetic predisposition, and an increased frequency of latent infection with prooncogenic viruses such as Epstein-Barr virus (EBV). The spontaneous remission of lymphomas in eight RA patients after MTX was stopped highlights the likely causative role of the drug in the development of these malignancies. If the clinical situation permits, a period of observation for spontaneous remission after MTX is stopped is advisable. The physicians caring for RA patients on MTX should maintain a high surveillance for signs and symptoms suggestive of lymphoma.

Ovulation induction and in vitro fertilization in systemic lupus erythematosus and antiphospholipid syndrome

OBJECTIVE During ovulation induction (OI), ovarian stimulation is accomplished by hormonal manipulation, which includes administration of gonadotropins, gonadotropin-releasing hormone agonists, follicle-stimulating hormone, and luteinizing hormone. In in vitro fertilization (IVF), progesterone is often added. Because of the possibility of hormone-associated flare or thrombosis, patients with systemic lupus erythematosus (SLE) and primary antiphospholipid syndrome (primary APS) undergoing OI/IVF are potentially at increased risk. The present study was conducted in order to assess this risk. METHODS Nineteen women who underwent 68 cycles of OI/IVF were studied by interview and retrospective chart review. RESULTS Four OI/IVF cycles (25%) in SLE patients resulted in increased lupus activity and 2 (13%) in ovarian hyperstimulation syndrome. One patient with primary APS who was given heparin during multiple cycles developed osteopenia. No thrombosis occurred. Pregnancy complications included toxemia, lupus flare, gastrointestinal hemorrhage due to Mallory-Weiss tear, polygestation, and diabetes. Postpartum complications included nephritis flare, costochondritis, and suicidal depression. Lupus flares occurred at expected rates. Five of 16 cycles (31%) in 7 SLE patients, 5 of 48 cycles (10%) in 10 primary APS patients, and 0 of 5 cycles in 2 women with antiphospholipid antibody (without SLE or primary APS) resulted in liveborn children, including multiple gestations (3 twin sets with 4 surviving infants and 2 triplet sets with 3 surviving infants). Seven of 14 living children (50%) were premature, 3 had neonatal lupus, and 1 had pulmonic stenosis. Five surviving infants (38%) had complications unrelated to prematurity. CONCLUSION Although OI/IVF can be successful in SLE and primary APS patients, rates of fetal and maternal complications are high.

Recognizing and managing comorbidities in psoriatic arthritis.

Purpose of reviewMany patients with psoriatic arthritis (PsA) have additional medical problems that can have an impact on morbidity and mortality. The goal of this review is to summarize the available evidence to date on the association of medical comorbidities with PsA and the implications these comorbidities have on prognosis, therapy selection and treatment response. Recent findingsCardiovascular disease, metabolic syndrome, obesity, diabetes, fatty liver disease Crohns disease, ophthalmic disease, depression and anxiety are common comorbidities associated with PsA. Additional comorbidities may include an elevated risk for malignancy and osteoporosis; however, fewer studies have addressed these issues and the data available are sometimes conflicting. SummaryAll clinicians caring for patients with PsA should be aware of the relevant comorbidities affecting patients with PsA and should have an understanding of how these comorbidities affect management.

Does route of administration affect the outcome of TNF antagonist therapy

The tumor necrosis factor (TNF) antagonists are parenterally administered biologic response modifiers indicated for the management of rheumatoid arthritis. Although infliximab, etanercept, and adalimumab are all members of this class, they differ in route of administration and dosing regimen. In the USA and in Europe, infliximab, in combination with oral methotrexate, is administered intravenously, initially at a dose of 3 mg/kg at weeks 0, 2, and 6, then every 8 weeks thereafter. The US Food and Drug Administration (FDA) has further approved that the dosage can be increased to 10 mg/kg and the doses can be given as often as every 4 weeks to optimize patient outcome (information based on the US package insert dated June 2002). Etanercept and adalimumab are given subcutaneously and can be self-injected. The FDA-approved dose of etanercept is 25 mg twice weekly, and of adalimumab is 40 mg every 2 weeks with methotrexate, or 40 mg alone. Medication adherence, possibly the most important factor in maintaining the benefits of anti-TNF therapy, is influenced by the interaction between the patient and his or her healthcare team, the patients attitude toward the disease and medication regimen, and the choice of therapy.

Inflammation and autoantibody markers identify rheumatoid arthritis patients with enhanced clinical benefit following rituximab treatment

OBJECTIVE Rituximab significantly improves the signs and symptoms of rheumatoid arthritis (RA) and slows the progression of joint damage. The aim of this study was to identify clinical characteristics and biomarkers that identify patients with RA in whom the clinical benefit of rituximab may be enhanced. METHODS The study group comprised 1,008 RA patients from 2 independent randomized placebo-controlled phase III clinical trials (REFLEX [Randomized Evaluation of Long-Term Efficacy of Rituximab in Rheumatoid Arthritis] and SERENE [Study Evaluating Rituximabs Efficacy in Methotrexate Inadequate Responders]). A novel threshold selection method was used to identify baseline candidate biomarkers present in at least 20% of patients that enriched for placebo-corrected American College of Rheumatology 50% improvement (ACR50 response; a high clinical efficacy bar) at week 24 after the first course of rituximab. RESULTS The presence of IgM rheumatoid factor (IgM-RF), IgG-RF, IgA-RF, and IgG anti-cyclic citrullinated peptide (anti-CCP) antibodies together with an elevated C-reactive protein (CRP) level were associated with enhanced placebo-corrected ACR50 response rates in the REFLEX patients with RA who had an inadequate response to anti-tumor necrosis factor therapies. These findings were independently replicated using samples from patients in SERENE who had an inadequate response to disease-modifying antirheumatic drug treatment. The combination of an elevated baseline CRP level together with an elevated level of any RF isotype and/or IgG anti-CCP antibodies was further associated with an enhanced benefit to rituximab. CONCLUSION The presence of any RF isotype and/or IgG anti-CCP autoantibodies together with an elevated CRP level identifies a subgroup of patients with RA in whom the benefit of rituximab treatment may be enhanced. Although the clinical benefit of rituximab was greater in the biomarker-positive population compared with the biomarker-negative population, the clinical benefit of rituximab compared with placebo was also clinically meaningful in the biomarker-negative population.

Do anti-TNF agents have equal efficacy in patients with rheumatoid arthritis?

Tumor necrosis factor (TNF) antagonists have dramatically improved the outcomes of rheumatoid arthritis (RA). Three agents currently available in the USA – infliximab, etanercept, and adalimumab – have been designed to modify the biologic effects of TNF. Infliximab and adalimumab are monoclonal antibodies, and etanercept is a soluble protein. The pharmacokinetic and pharmacodynamic properties of each differs significantly from those of the others. All three agents are effective and safe, and can improve the quality of life in patients with RA. Although no direct comparisons are available, clinical trials provide evidence that can be used to evaluate the comparative efficacy of these agents. Infliximab, in combination with methotrexate, has been shown to relieve the signs and symptoms of RA, decrease total joint score progression, prevent joint erosions and joint-space narrowing, and improve physical function for up to 2 years. Etanercept has been shown to relieve the signs and symptoms of RA, decrease total joint score progression, and slow the rate of joint destruction, and might improve physical function. Etanercept is approved with and without methotrexate for patients who have demonstrated an incomplete response to therapy with methotrexate and other disease-modifying anti-rheumatic drugs (DMARDs), as well as for first-line therapy in early RA, psoriatic arthritis, and juvenile RA. Adalimumab relieves the signs and symptoms of RA with and without methotrexate and other DMARDs, decreases total joint score progression, prevents joint erosions and joint-space narrowing in combination with methotrexate, and might improve physical function. When selecting a TNF antagonist, rheumatologists should weigh evidence and experience with specific agents before a decision is made for use in therapy.

A series of critically challenging case scenarios in moderate to severe psoriasis: A Delphi consensus approach

Clinical trials for systemic psoriasis therapy typically enroll healthy patients and exclude patients with cardiovascular disease, latent tuberculosis, liver disease, histories of malignancies, viral infections, children, and pregnant or breast-feeding women. Physicians often require guidance for optimum management of severe psoriasis in patients that have a combination of underlying disease states. To provide treatment recommendations for complex psoriasis scenarios, a consensus panel comprising 15 experts in psoriatic disease convened to review and discuss available evidence-based data and to arrive at a consensus for treatment options of difficult cases. An application of the Delphi Method was used to select case scenarios, provide medical treatment options, present the case study with existing medical evidence, and anonymously vote on treatment options. The top 10 treatment options were ranked and statistically analyzed to compare the differences between treatments. The final rankings and analysis provide guidance for practical, safe, and efficacious treatment options in a number of complex psoriasis scenarios.

Comprehensive treatment of psoriatic arthritis: Managing comorbidities and extraarticular manifestations

Psoriatic arthritis (PsA) is an inflammatory arthritis associated with psoriasis that can lead to decreased health-related quality of life and permanent joint damage leading to functional decline. In addition to joint and skin manifestations, both psoriasis and PsA are associated with numerous comorbidities and extraarticular/cutaneous manifestations, which may influence the physician’s choice of therapy. The objectives of this review are (1) to identify comorbidities in patients with PsA based on the available evidence; (2) to examine the effects of these comorbidities or extraarticular/cutaneous manifestation on the management of patients with PsA as well as the selection of therapy; and (3) to highlight research needs around comorbidities and treatment paradigms. This review is part of a treatment recommendations update initiated by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).