A double-blind, placebo-controlled, phase II, randomized study of lovastatin therapy in the treatment of mildly active rheumatoid arthritis.

OBJECTIVES: 3-hydroxy-3-methylglutaryl coenzyme-A (HMG Co-A) reductase inhibitors (statins) are standard treatment for hyperlipidaemia. In addition to lipid-lowering abilities, statins exhibit multiple anti-inflammatory effects. The objectives of this study were to determine whether treatment of patients with RA with lovastatin decreased CRP or reduced disease activity. METHODS: We conducted a randomized double-blind placebo-controlled 12 week trial of lovastatin vs placebo in 64 RA patients with mild clinical disease activity but an elevated CRP. The primary efficacy end point was the reduction in mean log CRP. Secondary end points included disease activity, RF and anti-CCP antibody titres. Mechanistic end points included levels of serum cytokines. Safety was assessed; hepatic and muscle toxicities were of particular interest. RESULTS: Baseline features were similar between groups. No significant difference in mean log CRP reduction between the two groups was observed, and disease activity did not change from baseline in either treatment group. Mechanistic analyses did not reveal significant changes in any biomarkers. A post hoc analysis of subjects not using biologic therapy demonstrated a significantly greater proportion achieving ⩾20% reduction in CRP from baseline in the lovastatin group compared with placebo (P-value = 0.007). No difference was observed in subjects receiving biologics. Lovastatin was well tolerated with no serious safety concerns. CONCLUSION: This study showed no anti-inflammatory or clinical effects on RA disease activity after 12 weeks of treatment with lovastatin. Lovastatin had a modest effect on CRP in subjects not using biologics, suggesting statins may be anti-inflammatory in selected patients. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, NCT00302952.

An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis.

Tuberculosis (TB), caused by infection with Mycobacterium tuberculosis, is a major cause of morbidity and mortality worldwide. Efforts to control it are hampered by difficulties with diagnosis, prevention and treatment. Most people infected with M. tuberculosis remain asymptomatic, termed latent TB, with a 10% lifetime risk of developing active TB disease. Current tests, however, cannot identify which individuals will develop disease. The immune response to M. tuberculosis is complex and incompletely characterized, hindering development of new diagnostics, therapies and vaccines. Here we identify a whole-blood 393 transcript signature for active TB in intermediate and high-burden settings, correlating with radiological extent of disease and reverting to that of healthy controls after treatment. A subset of patients with latent TB had signatures similar to those in patients with active TB. We also identify a specific 86-transcript signature that discriminates active TB from other inflammatory and infectious diseases. Modular and pathway analysis revealed that the TB signature was dominated by a neutrophil-driven interferon (IFN)-inducible gene profile, consisting of both IFN-gamma and type I IFN-alphabeta signalling. Comparison with transcriptional signatures in purified cells and flow cytometric analysis suggest that this TB signature reflects changes in cellular composition and altered gene expression. Although an IFN-inducible signature was also observed in whole blood of patients with systemic lupus erythematosus (SLE), their complete modular signature differed from TB, with increased abundance of plasma cell transcripts. Our studies demonstrate a hitherto underappreciated role of type I IFN-alphabeta signalling in the pathogenesis of TB, which has implications for vaccine and therapeutic development. Our study also provides a broad range of transcriptional biomarkers with potential as diagnostic and prognostic tools to combat the TB epidemic.

Placebo-controlled trial of tofacitinib monotherapy in rheumatoid arthritis.

BACKGROUND: Tofacitinib (CP-690,550) is a novel oral Janus kinase inhibitor that is being investigated as a targeted immunomodulator and disease-modifying therapy for rheumatoid arthritis. METHODS: In this phase 3, double-blind, placebo-controlled, parallel-group, 6-month study, 611 patients were randomly assigned, in a 4:4:1:1 ratio, to 5 mg of tofacitinib twice daily, 10 mg of tofacitinib twice daily, placebo for 3 months followed by 5 mg of tofacitinib twice daily, or placebo for 3 months followed by 10 mg of tofacitinib twice daily. The primary end points, assessed at month 3, were the percentage of patients with at least a 20% improvement in the American College of Rheumatology scale (ACR 20), the change from baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) scores (which range from 0 to 3, with higher scores indicating greater disability), and the percentage of patients with a Disease Activity Score for 28-joint counts based on the erythrocyte sedimentation rate (DAS28-4[ESR]) of less than 2.6 (with scores ranging from 0 to 9.4 and higher scores indicating more disease activity). RESULTS: At month 3, a higher percentage of patients in the tofacitinib groups than in the placebo groups met the criteria for an ACR 20 response (59.8% in the 5-mg tofacitinib group and 65.7% in the 10-mg tofacitinib group vs. 26.7% in the combined placebo groups, P<0.001 for both comparisons). The reductions from baseline in HAQ-DI scores were greater in the 5-mg and 10-mg tofacitinib groups than in the placebo groups (-0.50 and -0.57 points, respectively, vs. -0.19 points; P<0.001). The percentage of patients with a DAS28-4(ESR) of less than 2.6 was not significantly higher with tofacitinib than with placebo (5.6% and 8.7% in the 5-mg and 10-mg tofacitinib groups, respectively, and 4.4% with placebo; P=0.62 and P=0.10 for the two comparisons). Serious infections developed in six patients who were receiving tofacitinib. Common adverse events were headache and upper respiratory tract infection. Tofacitinib treatment was associated with elevations in low-density lipoprotein cholesterol levels and reductions in neutrophil counts. CONCLUSIONS: In patients with active rheumatoid arthritis, tofacitinib monotherapy was associated with reductions in signs and symptoms of rheumatoid arthritis and improvement in physical function. (Funded by Pfizer; ORAL Solo ClinicalTrials.gov number, NCT00814307.).

Home-Based Telemedicine in Rheumatology-A Scoping Review.

OBJECTIVE: We performed a scoping review of the relevant literature on home-based telehealth in rheumatology to understand its appropriate application in rheumatology practice. METHODS: We searched the Cochrane Library, PubMed, Web of Science, and scientific meeting abstracts to identify articles that specifically addressed telehealth suitability, barriers to telehealth, patient-reported outcomes (PROs) collected in telehealth settings, and telehealth satisfaction. From the initial search of 4,882 studies, 23 reports were included. In addition, 10 abstracts were also eligible for analysis, resulting in a total of 33 articles: 2 randomized clinical trials, 9 prospective cohort studies, and 22 retrospective studies. RESULTS: We found that triage appointments or predictive models could be helpful in selecting patients for telehealth and that telehealth interventions were appropriate for follow-up of patients with systemic lupus erythematosus and inflammatory arthritis, but that conducting new patient visits over telehealth was not ideal. Barriers to telehealth include patient factors (age, technology access) and need for physician/process factors (eg, physical examinations). PROs collected in regular practice can be incorporated into telehealth. Several small, single-center studies suggest that telehealth does not lead to negative outcomes compared with in-person visits, and overall, patients report high patient satisfaction with telehealth. In several scenarios, home-based telehealth was equivalent to in-person visits with regard to patient outcomes and satisfaction. CONCLUSION: The widespread potential of telehealth to manage and deliver care for people with rheumatic disease is significant. As such, further research in the form of randomized controlled trials can help contribute to growing evidence that shapes telehealth implementation for patients with rheumatic diseases.

Interferon-γ release assay versus tuberculin skin test prior to treatment with golimumab, a human anti-tumor necrosis factor antibody, in patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis.

OBJECTIVE: To evaluate the performance of an interferon-γ release assay (IGRA) versus the standard tuberculin skin test (TST) as a screening tool for latent tuberculosis (TB) infection prior to the initiation of anti-tumor necrosis factor therapy in patients with autoimmune inflammatory diseases. METHODS: This integrated analysis involved screening of patients with rheumatoid arthritis, those with psoriatic arthritis, and those with ankylosing spondylitis from phase III trials of golimumab. The IGRA used to screen for latent TB was the QuantiFERON-TB Gold In-Tube test. RESULTS: In this pooled analysis, 2,282 patients underwent both IGRA and TST screening prior to golimumab treatment. Among these patients, 13.8% had at least one test yielding positive findings for latent TB, including 9.4% with positive results by TST, 7.0% with positive results by IGRA, and 2.6% with positive results on both tests. The rate of indeterminate results for TB on IGRA was 1.8%. Agreement between the TST and IGRA results, measured by the kappa coefficient, was 0.22 (95% confidence interval 0.157-0.279; P=0.021). Among the patients with positive IGRA findings, 36.9% had positive TST findings. Among the patients with positive TST findings, 27.4% had positive IGRA findings. Overall, 781 (34.2%) of the 2,282 patients had previously received the bacillus Calmette-Guérin (BCG) vaccine; among this vaccinated group, the rate of positivity for latent TB by TST was 15.2% (119 of 781), compared to a rate of positivity of 9.1% (71 of 781) by IGRA (P=0.0002). Among patients who had not received the BCG vaccine, the rate of positivity by TST was 5.0% (62 of 1,248) and the rate of positivity by IGRA was 5.8% (72 of 1,248) (P=0.3745). When the IGRA was repeated in patients whose results were initially indeterminate, the rate of indeterminate IGRA findings for latent TB was much lower than has been previously reported. CONCLUSION: In the absence of a true gold standard test for latent TB infection, results of this comparison of IGRA and TST in a large cohort of patients with rheumatic diseases suggest that the IGRA provides greater specificity and possibly greater sensitivity than the TST.

Rheumatoid Arthritis: Early Diagnosis and Treatment.

Rheumatoid arthritis (RA) is a chronic, progressive inflammatory disorder that manifests as a symmetric polyarthritis of small and large joints that may lead to joint and periarticular structural damage and the consequences of systemic inflammation. This overview of early RA examines the unmet needs and challenges in RA, how to best diagnose RA, and pitfalls in early diagnosis and treatment. The rules for referral to a rheumatologist are reviewed. Primary care physicians are at the front line of early diagnosis and need to start disease-modifying therapy as soon as a diagnosis of RA is established.

Rheumatoid Arthritis: Early Diagnosis and Treatment.

Rheumatoid arthritis (RA) is a chronic, progressive inflammatory disorder that manifests as a symmetric polyarthritis of small and large joints that may lead to joint and periarticular structural damage and the consequences of systemic inflammation. This overview of early RA examines the unmet needs and challenges in RA, how to best diagnose RA, and pitfalls in early diagnosis and treatment. The rules for referral to a rheumatologist are reviewed. Primary care physicians are at the front line of early diagnosis and need to start disease-modifying therapy as soon as a diagnosis of RA is established.

Assessing rheumatologists' attitudes and utilization of classification criteria for ankylosing spondylitis and axial spondyloarthritis: a global effort.

OBJECTIVES: This study aims to assess rheumatologists' perceptions, utilization patterns, and attitudes towards the modified New York (mNY) criteria for ankylosing spondylitis (AS) and Assessment of SpondyloArthritis International Society (ASAS) criteria for axial spondyloarthritis (axSpA). METHODS: Members of the national rheumatology societies in five countries (United States of America (USA), Canada, India, Turkey, and Brazil) were invited to participate in a survey containing questions regarding rheumatologists' familiarity, and use of AS and axSpA classification criteria in daily practice, perceived specificity of spondyloarthritis features in making the diagnosis, patterns of imaging tests performed in daily practice, and their opinion about the need for modification of current classification criteria. The responses were analyzed by gender, age, years in practice, as well as by country of practice. Descriptive statistics, t test, and chi-square test were used for comparison of groups. RESULTS: Approximately 6% rheumatologists (478 out of 8021 professional association members) from five countries completed the survey. The country-specific response rates were Brazil 4%, USA 4.3%, India 11%, Canada 14%, and Turkey 29%, though the overall contributions from individual countries were USA 47%, India 14.9%, Brazil 13.8%, Turkey 12.8%, and Canada 8.8%. The mean age of respondents was 50 years (± 11.8), 31% were females and 90% spent majority (> 75%) of their time in clinical practice. The mNY and ASAS criteria were regularly used in clinical practice by 44 and 66% of responders, respectively. Those reporting "always" using ASAS criteria were more likely to be women (p = 0.006), and within 5 years of completing rheumatology training. Vast majority (74%) regarded Inflammatory Back Pain (IBP) as a specific feature for axSpA. Majority (50 and 60%, respectively) regarded uveitis and dactylitis as "very specific" features helping them make the diagnosis of axSpA, whereas heel enthesitis, peripheral inflammatory arthritis, and response to NSAIDs were considered "somewhat specific" by 50% of the responders. Less than half (47%) of the responders used the mNY grading for X-ray of SI joints. In the case of normal X-ray of SI joint, the use of MRI was more frequent than CT scan (83.6 vs. 10.9%) in assessing for sacroiliitis. If sacroiliitis was not seen on X-rays, the likelihood of ordering MRI was significantly higher among rheumatologists completing training within < 15 years versus > 25 years prior (90 vs. 75%, p = 0.007). Overall, 70% thought that ASAS criteria were adequately specific for clinical trials. However, 42% respondents still felt a need to modify ASAS classification criteria for axSpA. Also, 46% respondents felt that mNY criteria should be modified. CONCLUSIONS: In the absence of diagnostic criteria, majority of rheumatologists are using the classification criteria for diagnosis of axSpA. Though axSpA classification criteria are perceived to be specific for clinical trials, 40% rheumatologists feel the need to modify these criteria. Key Points • This study informs how rheumatologists in five countries spread over four different continents diagnose axSpA in clinical practice. • Since majority rheumatologists among survey respondents across the countries use ASAS criteria for diagnosis of axSpA, more specific criteria may be required to avoid overdiagnosis. • MRI is commonly used to rule out sacroiliitis in case of normal X-ray of sacroiliac joints.

Perceptions of Pregnancy and Lactation from the Pregnancy and Lactation Autoimmune Network Registry.

OBJECTIVE: The Pregnancy and Lactation Autoimmune Network (PLAN) registry was established to evaluate the concerns of women with autoimmune or inflammatory rheumatic diseases (AIRD) pertaining to pregnancy and lactation. METHODS: The registry was started as a survey of patients with AIRD at a single rheumatology specialty center in November 2016 and included questions regarding fertility, pregnancy, miscarriages, and lactation before and after diagnosis. RESULTS: The study included 154 subjects from the PLAN registry. More than half (52%) of respondents indicated that their diagnosis negatively changed their views on pregnancy and nearly a third (30%) decided not to have children after AIRD diagnosis. Most (66%) women were concerned that medication use during the childbearing process would affect the baby. One-third (34%) indicated their views on breastfeeding negatively changed as a result of their disease diagnosis. The rates and duration of breastfeeding did not differ significantly for babies born before or after the mothers' diagnosis (p = 0.50 and p = 0.21, respectively). Eighteen women in our study avoided breastfeeding or stopped breastfeeding earlier than planned to start a medication (including etanercept, adalimumab, hydroxychloroquine, and certolizumab) they believed to be contraindicated during lactation. The PLAN registry included 19 women who breastfed 22 babies while being exposed to a disease-modifying antirheumatic drug or biologic. None of these 19 women reported a delay in their children's developmental milestones or higher infection rates. CONCLUSION: This study highlights an unmet need in patients with AIRD of childbearing potential for data and education regarding pregnancy and lactation.

2020 American College of Rheumatology Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases.

OBJECTIVE: To develop an evidence-based guideline on contraception, assisted reproductive technologies (ART), fertility preservation with gonadotoxic therapy, use of menopausal hormone replacement therapy (HRT), pregnancy assessment and management, and medication use in patients with rheumatic and musculoskeletal disease (RMD). METHODS: We conducted a systematic review of evidence relating to contraception, ART, fertility preservation, HRT, pregnancy and lactation, and medication use in RMD populations, using Grading of Recommendations Assessment, Development and Evaluation methodology to rate the quality of evidence and a group consensus process to determine final recommendations and grade their strength (conditional or strong). Good practice statements were agreed upon when indirect evidence was sufficiently compelling that a formal vote was unnecessary. RESULTS: This American College of Rheumatology guideline provides 12 ungraded good practice statements and 131 graded recommendations for reproductive health care in RMD patients. These recommendations are intended to guide care for all patients with RMD, except where indicated as being specific for patients with systemic lupus erythematosus, those positive for antiphospholipid antibody, and/or those positive for anti-Ro/SSA and/or anti-La/SSB antibodies. Recommendations and good practice statements support several guiding principles: use of safe and effective contraception to prevent unplanned pregnancy, pre-pregnancy counseling to encourage conception during periods of disease quiescence and while receiving pregnancy-compatible medications, and ongoing physician-patient discussion with obstetrics/gynecology collaboration for all reproductive health issues, given the overall low level of available evidence that relates specifically to RMD. CONCLUSION: This guideline provides evidence-based recommendations developed and reviewed by panels of experts and RMD patients. Many recommendations are conditional, reflecting a lack of data or low-level data. We intend that this guideline be used to inform a shared decision-making process between patients and their physicians on issues related to reproductive health that incorporates patients' values, preferences, and comorbidities.

2020 American College of Rheumatology Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases.

OBJECTIVE: To develop an evidence-based guideline on contraception, assisted reproductive technologies (ART), fertility preservation with gonadotoxic therapy, use of menopausal hormone replacement therapy (HRT), pregnancy assessment and management, and medication use in patients with rheumatic and musculoskeletal disease (RMD). METHODS: We conducted a systematic review of evidence relating to contraception, ART, fertility preservation, HRT, pregnancy and lactation, and medication use in RMD populations, using Grading of Recommendations Assessment, Development and Evaluation methodology to rate the quality of evidence and a group consensus process to determine final recommendations and grade their strength (conditional or strong). Good practice statements were agreed upon when indirect evidence was sufficiently compelling that a formal vote was unnecessary. RESULTS: This American College of Rheumatology guideline provides 12 ungraded good practice statements and 131 graded recommendations for reproductive health care in RMD patients. These recommendations are intended to guide care for all patients with RMD, except where indicated as being specific for patients with systemic lupus erythematosus, those positive for antiphospholipid antibody, and/or those positive for anti-Ro/SSA and/or anti-La/SSB antibodies. Recommendations and good practice statements support several guiding principles: use of safe and effective contraception to prevent unplanned pregnancy, pre-pregnancy counseling to encourage conception during periods of disease quiescence and while receiving pregnancy-compatible medications, and ongoing physician-patient discussion with obstetrics/gynecology collaboration for all reproductive health issues, given the overall low level of available evidence that relates specifically to RMD. CONCLUSION: This guideline provides evidence-based recommendations developed and reviewed by panels of experts and RMD patients. Many recommendations are conditional, reflecting a lack of data or low-level data. We intend that this guideline be used to inform a shared decision-making process between patients and their physicians on issues related to reproductive health that incorporates patients' values, preferences, and comorbidities.

Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis.

BACKGROUND: Glucosamine and chondroitin sulfate are used to treat osteoarthritis. The multicenter, double-blind, placebo- and celecoxib-controlled Glucosamine/chondroitin Arthritis Intervention Trial (GAIT) evaluated their efficacy and safety as a treatment for knee pain from osteoarthritis. METHODS: We randomly assigned 1583 patients with symptomatic knee osteoarthritis to receive 1500 mg of glucosamine daily, 1200 mg of chondroitin sulfate daily, both glucosamine and chondroitin sulfate, 200 mg of celecoxib daily, or placebo for 24 weeks. Up to 4000 mg of acetaminophen daily was allowed as rescue analgesia. Assignment was stratified according to the severity of knee pain (mild [N=1229] vs. moderate to severe [N=354]). The primary outcome measure was a 20 percent decrease in knee pain from baseline to week 24. RESULTS: The mean age of the patients was 59 years, and 64 percent were women. Overall, glucosamine and chondroitin sulfate were not significantly better than placebo in reducing knee pain by 20 percent. As compared with the rate of response to placebo (60.1 percent), the rate of response to glucosamine was 3.9 percentage points higher (P=0.30), the rate of response to chondroitin sulfate was 5.3 percentage points higher (P=0.17), and the rate of response to combined treatment was 6.5 percentage points higher (P=0.09). The rate of response in the celecoxib control group was 10.0 percentage points higher than that in the placebo control group (P=0.008). For patients with moderate-to-severe pain at baseline, the rate of response was significantly higher with combined therapy than with placebo (79.2 percent vs. 54.3 percent, P=0.002). Adverse events were mild, infrequent, and evenly distributed among the groups. CONCLUSIONS: Glucosamine and chondroitin sulfate alone or in combination did not reduce pain effectively in the overall group of patients with osteoarthritis of the knee. Exploratory analyses suggest that the combination of glucosamine and chondroitin sulfate may be effective in the subgroup of patients with moderate-to-severe knee pain. (ClinicalTrials.gov number, NCT00032890.).

Unresolved issues in identifying and overcoming inadequate response in rheumatoid arthritis: weighing the evidence.

Rheumatoid arthritis (RA) is a chronic, multisystem, inflammatory disorder of the joints that affects about 1% of the world population. The ultimate goals of therapy include remission of disease and prevention of joint damage. Reaching these goals has become a realistic outcome for an increasing number of patients as treatment options have expanded over the past 3 decades. In addition to older therapies, such as methotrexate (MTX), other disease modifying drugs (DMARD), and tumor necrosis factor (TNF) inhibitors, newer biologic treatments have become available. For the substantial number of patients who experience an inadequate response to standard medications, biologic response modifiers (BRM) provide an important therapeutic alternative. The availability of multiple treatment options in the absence of clear definitions or criteria for remission and inadequate response, however, makes clinical decisions about measuring outcomes, predicting response to treatment, and prescribing pharmacologic therapies challenging. In this program, distinguished rheumatologists weigh the evolving body of clinical evidence to draw sound conclusions and resolve key issues in managing inadequate response to treatment and in achieving optimal outcomes in RA.

Routine Use of Quantitative Disease Activity Measurements among US Rheumatologists: Implications for Treat-to-target Management Strategies in Rheumatoid Arthritis.

OBJECTIVE: The aim of our study was to examine why real-world practices and attitudes regarding quantitative measurements of rheumatoid arthritis (RA) have received limited attention. METHODS: An e-mail survey asked US rheumatologists to self-report on their use of quantitative measurements (metric). RESULTS: Among 439 respondents, metric rheumatologists (58%) were more likely to be in group practice and to use tumor necrosis factor inhibitors. The quantitative tools most commonly used were the Health Assessment Questionnaire (35.5%) and the Routine Assessment of Patient Index Data 3 (27.1%). Reasons for not measuring included time needed and electronic availability. Based on simulated case scenarios, providing more quantitative information increased the likelihood that a patient would change to a different disease-modifying antirheumatic drug or biologic. CONCLUSION: Routine use of quantitative measurement for patients in the United States with RA is increasing over time but remains low.

Pregnancy Outcomes After Exposure to Certolizumab Pegol: Updated Results From a Pharmacovigilance Safety Database.

OBJECTIVE: Anti-tumor necrosis factor (anti-TNF) medications are effective in controlling chronic inflammatory diseases, but information about their use and safety in pregnancy is limited. Consequently, anti-TNF agents are often discontinued early in gestation. Certolizumab pegol (CZP), a PEGylated, Fc-free anti-TNF agent approved for the treatment of rheumatic diseases and/or Crohn's disease, has minimal to no active placental transfer. This analysis was undertaken to evaluate pregnancy outcomes in women receiving CZP, especially those exposed during early pregnancy. METHODS: Prospective and retrospective data on maternal CZP exposure were extracted from the UCB Pharma safety database through March 6, 2017. Analysis was limited to prospective reports to avoid potential bias associated with retrospective submissions. The numbers of live births, miscarriages, elective abortions, stillbirths, and major congenital malformations were ascertained. RESULTS: Of 1,137 prospectively reported pregnancies with maternal exposure to CZP, 528 (including 10 twin pregnancies) had 538 known outcomes: 459 live births (85.3%), 47 miscarriages (8.7%), 27 elective abortions (5.0%), and 5 stillbirths (0.9%). There were 8 major congenital malformations (1.7%) among the 459 infants. First trimester exposure occurred in 367 (81.2%) of 452 pregnancies resulting in 459 live births. Exposure during all 3 trimesters occurred in 201 (44.5%) of 452 pregnancies. CONCLUSION: This analysis represents the largest cohort of pregnant women exposed to an anti-TNF agent for management of chronic inflammatory diseases. Analysis of pregnancy outcomes does not indicate a teratogenic effect of CZP, compared to the general population, nor an increased risk of fetal death. The data are reassuring for women of childbearing age considering treatment with CZP.

Iatrogenic rheumatic syndromes in the elderly.

Rheumatic complaints are common in the geriatric population. However, uncommonly autoimmune or musculoskeletal complaints and disorders may arise as a consequence of pharmacotherapy. These rare events include stain myopathy, drug-induced lupus, arthralgias, vasculitis, or tight skin syndromes. This article discusses the possible iatrogenic causes of rheumatic conditions, potential inciting agents, and the various types of rheumatic manifestations seen in the elderly.

Early rheumatoid arthritis -- is there a window of opportunity?

The early diagnosis and treatment of nascent rheumatoid arthritis (RA) has become a prime objective for rheumatologists and clinicians who care for patients with arthritis. Population-based studies have consistently shown that patients with RA are at substantial risk for progressive joint damage, disability, and increased morbidity and mortality. These inevitable outcomes are closely linked to the consequences of rheumatoid inflammation, which begins early and is progressive in all. At issue is whether early diagnosis, coupled with aggressive therapy, might alter the natural history of this RA. If this "window of opportunity" exists, then outcomes should be substantially altered by delivering the right therapies at the right time. A growing body of evidence has emphasized the consistent clinical and radiographic benefits of early, aggressive treatment of RA. These studies confirm that all therapies - monotherapy, combination disease modifying antirheumatic drugs (DMARD), biologics - work better in early disease than in long-established RA. Earlier identification, referral, and an accurate diagnosis of RA can now be rewarded with highly effective DMARD or biologic therapies. Rheumatologists should rise to the challenge and educate clinicians about this window of opportunity, the potential for remission, and superior clinical responses when patients with early RA or undifferentiated arthritis are referred to and managed by experts in aggressive rheumatologic care.

Acute polyarthritis.

Arthritis is the most common cause of disability. Hence, prompt recognition and management of acute-onset polyarthritis are paramount to prevent progressive damage. When rheumatoid arthritis is considered as a prototypical example of polyarthritis, the stakes of early and accurate evaluation are evident. The challenge is in determining when undifferentiated polyarthritis ends and rheumatoid arthritis begins. This chapter reviews the evidence to help clinicians identify and manage patients who present with acute polyarticular inflammation.