BACKGROUND Despite current therapies, diffuse cutaneous systemic sclerosis (scleroderma) often has a devastating outcome. We compared myeloablative CD34+ selected autologous hematopoietic stem-cell transplantation with immunosuppression by means of 12 monthly infusions of cyclophosphamide in patients with scleroderma. METHODS We randomly assigned adults (18 to 69 years of age) with severe scleroderma to undergo myeloablative autologous stem-cell transplantation (36 participants) or to receive cyclophosphamide (39 participants). The primary end point was a global rank composite score comparing participants with each other on the basis of a hierarchy of disease features assessed at 54 months: death, event-free survival (survival without respiratory, renal, or cardiac failure), forced vital capacity, the score on the Disability Index of the Health Assessment Questionnaire, and the modified Rodnan skin score. RESULTS In the intention-to-treat population, global rank composite scores at 54 months showed the superiority of transplantation (67% of 1404 pairwise comparisons favored transplantation and 33% favored cyclophosphamide, P = 0.01). In the per-protocol population (participants who received a transplant or completed ≥9 doses of cyclophosphamide), the rate of event-free survival at 54 months was 79% in the transplantation group and 50% in the cyclophosphamide group (P = 0.02). At 72 months, Kaplan–Meier estimates of event-free survival (74% vs. 47%) and overall survival (86% vs. 51%) also favored transplantation (P = 0.03 and 0.02, respectively). A total of 9% of the participants in the transplantation group had initiated disease-modifying antirheumatic drugs (DMARDs) by 54 months, as compared with 44% of those in the cyclophosphamide group (P = 0.001). Treatment-related mortality in the transplantation group was 3% at 54 months and 6% at 72 months, as compared with 0% in the cyclophosphamide group. CONCLUSIONS Myeloablative autologous hematopoietic stem-cell transplantation achieved long-term benefits in patients with scleroderma, including improved event-free and overall survival, at a cost of increased expected toxicity. Rates of treatment-related death and post-transplantation use of DMARDs were lower than those in previous reports of nonmyeloablative transplantation. (Funded by the National Institute of Allergy and Infectious Diseases and the National Institutes of Health; ClinicalTrials.gov number, NCT00114530.)

These recommendations were developed based on a synthesis of international guidelines, supporting evidence, and expert consensus considering the Canadian healthcare context with the intention of promoting best practices and improving healthcare delivery for persons with RA.

Objective. To assess the efficacy of anakinra treatment in patients with adult-onset Still's disease (AOSD) that is refractory to corticosteroids, methotrexate (MTX), and etanercept.Methods. Four patients with AOSD were treated with prednisone and MTX and 2 patients were also treated with etanercept for worsening symptoms and indicators of systemic inflammation. White blood cells (WBCs), C-reactive protein (CRP) levels and/or erythrocyte sedimentation rate, and ferritin levels were measured and, in 1 patient, serum creatinine levels were determined. Treatment with anakinra at 100 mg/day was initiated.Results. The index patient's disease was refractory to treatment with prednisone (30 mg/day) and MTX, with spiking fevers, rash, synovitis, a serum ferritin level of 8,400 ng/ml (normal <200), and a CRP level of 86 mg/liter (normal <8). Levels of interleukin-1␤ (IL-1␤), IL-1␣, IL-6, IL-1 receptor antagonist, and IL-18 were elevated. Just prior to anakinra treatment, the WBC count was 14,600/mm 3 , the CRP level was 86 mg/liter, and the ferritin level was 573 ng/ml, with daily spiking fevers to 104°F, rash, and swollen joints. Within hours of the first injection, the patient was afebrile and asymptomatic; within days, the WBC count, ferritin level, and CRP level decreased into the normal range.On 2 occasions, anakinra was withheld. Within a few days, the WBC count rose to >20,000/mm 3 with prominent neutrophilia, the CRP level rose to >200 mg/liter, and the ferritin level rose to >3,000 ng/ml. Upon restarting anakinra, the patient became afebrile, the WBC count fell to 8,000/mm 3 , the CRP level fell to <3 mg/liter, and the ferritin level fell to <300 ng/ml. Three additional patients with refractory AOSD who experienced rapid reductions in fever, symptoms, and markers of inflammation when treated with anakinra are reported.Conclusion. Refractory AOSD appears to be IL-1-mediated since anakinra decreases hematologic, biochemical, and cytokine markers and also produces rapid reductions in systemic and local inflammation. Reported efficacy of tumor necrosis factor-blocking therapies in AOSD may be due to a reduction in IL-1.Adult-onset Still's disease (AOSD), a rheumatologic condition found worldwide, is characterized by a variety of clinical features, including intermittent fever, arthritis, evanescent rash, sore throat, leukocytosis, and hepatic dysfunction, polyserositis, lymphadenopathy, splenomegaly, and other systemic symptoms. Because of the diverse presentation (1), classifications have been developed to standardize the diagnosis of AOSD. The most widely accepted criteria set, as presented by Yamaguchi and colleagues (2), is a compilation of major and minor criteria with the exclusion of infections, malignancies, and other rheumatic or systemic diseases. More recently, Fautrel and associates have proposed classification criteria utilizing diagnostic markers of serum ferritin and glycosylated ferritin, thought to be more specific for AOSD (3). These criteria are said to provide a sensitivity of 80.6% and a specifi...

ABSTRACT. Objective. The Canadian Rheumatology Association (CRA) has developed recommendations for the pharmacological management of rheumatoid arthritis (RA) with traditional and biologic disease-modifying antirheumatic drugs (DMARD) in 2 parts. Part II, focusing on specific safety aspects of treatment with traditional and biologic DMARD in patients with RA, is reported here. Methods. Key questions were identified a priori based on results of a national needs-assessment survey. A systematic review of all clinical practice guidelines and consensus statements regarding treatment with traditional and biologic DMARD in patients with RA published between January 2000 and June 2010 was performed in Medline, Embase, and CINAHL databases, and was supplemented with a "grey literature" search including relevant public health guidelines. Systematic reviews of postmarketing surveillance and RA registry studies were performed to update included guideline literature reviews as appropriate. Guideline quality was independently assessed by 2 reviewers. Guideline characteristics, recommendations, and supporting evidence from observational studies and randomized trials were synthesized into evidence tables. The working group voted on recommendations using a modified Delphi technique.Results. Thirteen recommendations addressing perioperative care, screening for latent tuberculosis infection prior to the initiation of biologic DMARD, optimal vaccination practices, and treatment of RA patients with active or a history of malignancy were developed for rheumatologists, other primary prescribers of RA drug therapies, and RA patients. Conclusion. These recommendations were developed based on a synthesis of international RA and public health guidelines, supporting evidence, and expert consensus in the context of the Canadian health system. They are intended to help promote best practices and improve healthcare delivery for persons with RA. (First Release June 15 2012; J Rheumatol 2012;39:1583-602; doi:10.3899 Recommendations provided here are intended to be read in conjunction with the Canadian Rheumatology Association Recommendations for the Pharmacological Management of Rheumatoid Arthritis. These recommendations address specific safety questions that were identified a priori and are not intended to cover all safety aspects concerning treatment with traditional and biologic disease modifying antirheumatic drugs (DMARD).Traditional and biologic DMARD have greatly enhanced the care of persons with rheumatoid arthritis (RA); however, potential risks associated with their use need be considered. The Canadian Rheumatology Association (CRA) has developed recommendations for the pharmacological management of RA with traditional and biologic DMARD in 2 parts. Part I described the development process of CRA recommendations in detail and included 5 overarching RA care principles along with 26 treatment recommendations 1 . Part II, reported here, focuses on specific safety aspects of treatment with traditional and biologic DMARD in patients with ...

Early mortality in SSc is substantial, and prevalent cohorts underestimate mortality in SSc by failing to capture early deaths, particularly in men and those with diffuse disease.