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Robin K DoreDavid Geffen School of Medicine, Division of Rheumatology, UCLA, Los Angeles, CA, USAAbstract: Juvenile idiopathic arthritis (JIA) is a group of chronic inflammatory diseases affecting approximately 300,000 children and adolescents in the United States of unknown cause. It can affect children from the age of 0 years up to the age of 16 years. The International League of Associations of Rheumatology has defined seven subsets of JIA based on several factors including the number of affected joints and the involvement of other tissues; the prognosis for each affected child also depends on multiple factors including age of onset, number of joints involved, and systemic features. As with rheumatoid arthritis in adults, the goal of therapy is remission and resolution of disease activity; however, as a cure does not seem attainable in the near future, a reasonable goal of therapy is prevention of joint damage, inhibition of inflammation, and a high level of quality of life. Even with available therapies, many children with JIA enter adulthood with persistently active disease, suboptimal function, and impaired quality of life. Methotrexate remains the standard of care for children with JIA; etanercept was approved in 2000 in the United States for the treatment of JIA resistant to methotrexate. The efficacy and safety of etanercept therapy in children with JIA is reviewed and its place in the therapeutic regimen is discussed; the available long term data is also presented. The data presented was obtained from a PubMed search as well as a review of the references presented in the 2011 American College of Rheumatology Recommendations for the Treatment of Juvenile Idiopathic Arthritis and the 2013 Update. It is hoped that treatment with etanercept and other biologic therapies will lead to improved outcomes for children with JIA in the future.Keywords: juvenile idiopathic arthritis, juvenile chronic arthritis, juvenile rheumatoid arthritis, etanercept

Robin K DoreDavid Geffen School of Medicine, University of California, Los Angeles, CA, USAAbstract: Glucocorticoids are commonly prescribed medications to treat multiple diseases across many medical specialties. One of the most common yet largely unappreciated side effect of glucocorticoid use is increased risk of fracture. Many different therapies are indicated to prevent and treat this condition; many guidelines exist that suggest appropriate use of both glucocorticoids and the medications approved to prevent this common side effect of glucocorticoid therapy. Nevertheless, 30%–50% of patients on long-term glucocorticoid therapy sustain a fracture. Teriparatide, recombinant human parathyroid hormone (1–34), is a daily self-injectable therapy for 24 months approved for use in patients taking long-term glucocorticoids. Teriparatide has been shown to increase bone mineral density and reduce vertebral fracture risk in glucocorticoid-treated patients. Glucocorticoids have many adverse effects on bone that teriparatide has been shown to prevent or negate. Given the fact that preventive therapy for glucocorticoid-induced osteoporosis is often not prescribed, one wonders whether a daily self-injectable therapy for this condition would be prescribed by physicians and accepted by patients. This article reviews the epidemiology, pathophysiology, treatment, guidelines, and persistence data (when available) for patients with glucocorticoid-induced osteoporosis treated with teriparatide.Keywords: glucocorticoid-induced osteoporosis, teriparatide, anabolic, PTH, parathyroid hormone

OBJECTIVE: RANKL is essential for osteoclast development, activation, and survival. Denosumab is a fully human monoclonal IgG2 antibody that binds RANKL, inhibiting its activity. The aim of this multicenter, randomized, double-blind, placebo-controlled, phase II study was to evaluate the effects of denosumab on structural damage in patients with rheumatoid arthritis (RA) receiving methotrexate treatment. METHODS: RA patients received subcutaneous placebo (n = 75), denosumab 60 mg (n = 71), or denosumab 180 mg (n = 72) injections every 6 months for 12 months. The primary end point was the change from baseline in the magnetic resonance imaging (MRI) erosion score at 6 months. RESULTS: At 6 months, the increase in the MRI erosion score from baseline was lower in the 60-mg denosumab group (mean change 0.13; P = 0.118) and significantly lower in the 180-mg denosumab group (mean change 0.06; P = 0.007) than in the placebo group (mean change 1.75). A significant difference in the modified Sharp erosion score was observed as early as 6 months in the 180-mg denosumab group (P = 0.019) as compared with placebo, and at 12 months, both the 60-mg (P = 0.012) and the 180-mg (P = 0.007) denosumab groups were significantly different from the placebo group. Denosumab caused sustained suppression of markers of bone turnover. There was no evidence of an effect of denosumab on joint space narrowing or on measures of RA disease activity. Rates of adverse events were comparable between the denosumab and placebo groups. CONCLUSION: Addition of twice-yearly injections of denosumab to ongoing methotrexate treatment inhibited structural damage in patients with RA for up to 12 months, with no increase in the rates of adverse events as compared with placebo. [ABSTRACT FROM AUTHOR]

Objective: Comorbidities in rheumatoid arthritis (RA) can influence treatment selection, impact treatment persistency, and increase health care costs. This study assessed the magnitude of comorbidity burden via epidemiology (incidence and prevalence) and associated costs of select comorbidities in RA patients: anemia, malignancy, venous thromboembolism (VTE), major adverse cardiovascular events (MACE), and infections, stratified by history of disease-modifying antirheumatic drug (DMARD) exposure., Methods: From the IQVIA PharMetrics® Plus database, we selected adult patients with RA (2 or more RA diagnostic codes at least 30 days apart) at initiation of a new DMARD (DMARD-naïve), after the first conventional synthetic DMARD (csDMARD) or after the first biologic DMARD (bDMARD). We assessed pre-index prevalence (percentage) and on-treatment incidence (per 100 patient-years [P100PY]) of the aforementioned comorbidities. For patients with versus without incident conditions, we compared total all-cause health care costs as unadjusted and adjusted for baseline characteristics and health care costs., Results: Prior to initiating a new treatment, among DMARD-naïve patients (N = 28,201), csDMARD switchers (N = 7,816), or bDMARD switchers (N = 4,656), the overall prevalence ranged from 14.1% to 16.2% (anemia), from 1.3% to 5.2% (malignancy, evaluated in csDMARD and bDMARD switchers), from 1.5% to 2.1% (VTE), from 1.8% to 2.9% (MACE), and from 66.6% to 76.1% (infections). Once on index treatment, overall incidence (P100PY) among the cohorts ranged from 6.9 to 8.9 (anemia), from 2.0 to 2.3 (malignancy), from 0.7 to 0.9 (VTE), from 1.6 to 2.0 (MACE), and from 77.4 to 87.7 (infections). The incident comorbidities (except herpes zoster) were associated with increased adjusted health care costs., Conclusion: Anemia, malignancy, VTE, MACE, and infections affect patients with RA at all stages of their treatment journey and are associated with increased health care costs., (© 2021 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Abaloparatide increased ultradistal radius bone mineral density (BMD) in the Abaloparatide Comparator Trial in Vertebral Endpoints (ACTIVE) trial. Over the subsequent 24 months in ACTIVExtend, ultradistal radius BMD gains were maintained with alendronate. Conversely, 1/3 radius BMD remained stable during ALN treatment in ACTIVExtend after decreasing during ACTIVE., Introduction: Abaloparatide (ABL) increased femoral neck, total hip, and lumbar spine bone mineral density (BMD) in postmenopausal women with osteoporosis and decreased the risk of vertebral and nonvertebral fractures in ACTIVE. Effects on fracture risk and BMD were maintained subsequently with alendronate (ALN) in ACTIVExtend. In a prespecified subanalysis of ACTIVE, ABL also increased BMD at the ultradistal radius. Our objective was to determine the efficacy of ABL followed by ALN vs placebo (PBO) followed by ALN on forearm BMD and fracture risk over 43 months in ACTIVExtend., Methods: Ultradistal and 1/3 radius BMD (ACTIVE baseline to month 43) were measured (ABL/ALN, n = 213; PBO/ALN, n = 233). Wrist fracture rates were estimated for the ACTIVExtend intent-to-treat population (ABL/ALN, n = 558; PBO/ALN, n = 581) by Kaplan-Meier (KM) method., Results: At cumulative month 25, mean increase from ACTIVE baseline in ultradistal radius BMD was 1.1% (standard error, 0.49%) with ABL/ALN vs - 0.8% (0.43%) with PBO/ALN (P < 0.01). BMD increases with ABL were maintained with ALN through month 43 in ACTIVExtend. BMD decreases at the 1/3 radius in ACTIVE (similar with ABL and PBO) were maintained through 24 months of ALN treatment in ACTIVExtend. Wrist fractures over 43 months occurred in 15 women with ABL/ALN (KM estimate, 2.8%) and 20 with PBO/ALN (KM estimate, 3.6%) (HR = 0.77, 95% CI 0.39, 1.50; P = not significant)., Conclusion: Ultradistal radius BMD gains following treatment with ABL in ACTIVE were maintained over 24 months of ALN treatment in ACTIVExtend. Conversely, 1/3 radius BMD remained stable during ALN treatment in ACTIVExtend after decreasing during ACTIVE., Trial Registration: ClinicalTrials.gov : NCT01657162 submitted July 31, 2012.

In the randomized, placebo-controlled, double-blind phase 3 ACTIVE study (NCT01343004), 18 months of abaloparatide 80 μg daily (subcutaneous injection) in postmenopausal women at risk of osteoporotic fracture significantly reduced the risk of vertebral, nonvertebral, clinical, and major osteoporotic fractures and significantly increased bone mineral density (BMD) versus placebo regardless of baseline risk factors. Women from the abaloparatide and placebo groups who completed ACTIVE were eligible for ACTIVExtend (NCT01657162), in which all enrollees received sequential, open-label monotherapy with alendronate 70 mg once weekly for up to 24 months. This prespecified analysis evaluated whether fracture risk reductions and bone mineral density (BMD) gains associated with abaloparatide during ACTIVE persisted through the full 43-month ACTIVE-ACTIVExtend study period in nine prespecified baseline risk subgroups. Baseline risk subgroups included BMD T-score at the lumbar spine, total hip, and femoral neck (≤ - 2.5 versus > - 2.5 and ≤ -3.0 versus > - 3.0), history of nonvertebral fracture (yes/no), prevalent vertebral fracture (yes/no), and age (<65 versus 65 to <75 versus ≥75 years). Forest plots display treatment effect. Treatment-by-subgroup interactions were tested using the Breslow-Day test, Cox proportional hazards model, and ANCOVA model. After the combined ACTIVE-ACTIVExtend study period, reductions in relative risk for new vertebral, nonvertebral, clinical, and major osteoporotic fractures were greater among patients in the abaloparatide/alendronate group than among those in the placebo/alendronate group across all nine baseline risk subgroups. BMD gains at the lumbar spine, total hip, and femoral neck were greater in the abaloparatide/alendronate group versus the placebo/alendronate group. No clinically meaningful interaction between treatment assignment and any baseline risk variable was observed. The sequence of abaloparatide for 18 months followed by alendronate for up to 24 months appears to be an effective treatment option for a wide range of postmenopausal women at risk for osteoporotic fractures. © 2019 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc., (© 2019 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc.)

Purpose: In women with postmenopausal osteoporosis, we investigated the effects of 24 months of treatment with alendronate (ALN) following 18 months of treatment with abaloparatide (ABL) or placebo (PBO)., Methods: Women who completed ABL or PBO treatment in ACTIVE were eligible to receive up to 24 months of ALN. We evaluated the incidence of vertebral and nonvertebral fractures and changes in bone mineral density (BMD) during the entire 43-month period from ACTIVE baseline to the end of ACTIVExtend and for the 24-month extension only., Results: Five hundred fifty-eight women from ACTIVE's ABL group and 581 from its PBO group (92% of ABL and PBO completers) were enrolled. During the full 43-month treatment period, 0.9% of evaluable women in the ABL/ALN group experienced a new radiographic vertebral fracture vs 5.6% of women in the PBO/ALN group, an 84% relative risk reduction (RRR, P < 0.001). Kaplan-Meier incidence rates for other reported fracture types were significantly lower for ABL/ALN vs PBO/ALN (all P < 0.05). Gains in BMD achieved during ACTIVE were further increased during ACTIVExtend. For ACTIVExtend only, RRR for vertebral fractures was 87% with ABL/ALN vs PBO/ALN (P = 0.001). Adverse events were similar between groups. A supplemental analysis for regulatory authorities found no hip fractures in the ABL/ALN group vs five in the PBO/ALN group., Conclusions: Eighteen months of ABL followed by 24 months of ALN reduced the risk of vertebral, nonvertebral, clinical, and major osteoporotic fractures and increased BMD. Sequential ABL followed by ALN appears to be an effective treatment option for postmenopausal women at risk for osteoporosis-related fractures.

Osteoporosis and fractures that occur as a result of this condition pose a huge public health problem to society and result in morbidity and mortality to individuals. Because osteoporosis is often a result of aging, many people are not aware that therapies exist to reduce the risk of fracture. Until recently, the most common therapies used to treat osteoporosis, the oral bisphosphonates, had an inconvenient and cumbersome mode of administration. Within the last 4 years, two new parenteral antiresorptive drugs to treat osteoporosis were approved by the US Food and Drug Administration. As treatment of osteoporosis may extend for many years, the collection of long-term efficacy and safety data is warranted. This paper discusses data from the extension trials of denosumab and zoledronic acid.

Denosumab (Prolia) is a fully human monoclonal antibody directed against receptor activator of nuclear factor-κB ligand (RANKL), which interferes with the formation, activation, and survival of osteoclasts. It was approved by the Food and Drug Administration in June 2010 as a new treatment for postmenopausal osteoporosis in women who are at high risk for fracture. Given its mechanism of action, it is an antiresorptive therapy that is administered as a 60-mg subcutaneous injection every 6 months. It is the first biologic antiresorptive therapy for osteoporosis, and the first osteoporosis therapy to show efficacy and safety in patients with renal impairment., (Copyright © 2011. Published by Elsevier Inc.)

When prescribing glucocorticoids for long-term treatment, physicians should take steps to prevent osteoporosis, a common and serious side effect of these drugs.

Objectives: To report results of subgroup analyses of bone mineral density (BMD) and bone turnover markers from a randomised, double-blind, placebo-controlled, phase II study of denosumab, an investigational RANKL inhibitor, in patients with rheumatoid arthritis (RA) concurrently receiving treatment with bisphosphonates or glucocorticoids., Methods: Patients received subcutaneous placebo (n=75), denosumab 60 mg (n=71) or denosumab 180 mg (n=72) at baseline and 6 months. Assessments included dual x-ray absorptiometry scans of the lumbar spine and hip, and determination of levels of serum type I C-telopeptide (sCTx-I) and serum procollagen 1N-terminal peptide (P1NP)., Results: Denosumab treatment increased mean lumbar spine and hip BMD and reduced sCTx-I and P1NP compared with placebo through 12 months, regardless of baseline BMD or marker levels or concomitant bisphosphonate or glucocorticoid use., Conclusions: This study extends evidence that denosumab increases BMD and reduces bone turnover in patients with RA and may provide a new therapeutic option for reducing systemic bone loss in patients with RA.

Objective: Periarticular osteoporosis is one of the earliest radiographic signs of bone damage in rheumatoid arthritis (RA). Denosumab, an investigational fully human monoclonal antibody that binds to RANKL, inhibits bone erosion and systemic bone loss in clinical studies of patients with RA. In this hand bone mineral density (BMD) substudy, we investigated the effects of denosumab on hand BMD and its correlation with hand erosion scores., Methods: Patients receiving methotrexate for erosive RA were randomized in a 1:1:1 ratio to receive subcutaneous placebo, denosumab 60 mg, or denosumab 180 mg at 0 and 6 months. Measurements included BMD (by dual x-ray absorptiometry [DXA]) of both hands (0, 1, 6, and 12 months), magnetic resonance images of the hands/wrists (0 and 6 months), and radiographs of the hands/wrists and feet (0, 6, and 12 months)., Results: There were 56 patients (13 placebo, 21 denosumab 60 mg, and 22 denosumab 180 mg). Mean changes in hand BMD at 6 and 12 months were: +0.8% and +1.0%, respectively, for denosumab 60 mg; +2.0% and +2.5%, respectively, for denosumab 180 mg; and -1.2% and -2.0%, respectively, for placebo. Erosion scores remained near baseline in the denosumab groups and increased from baseline in the placebo group. A negative correlation was observed between hand BMD and erosion scores., Conclusion: In patients with RA, denosumab provided protection against erosion, and not only prevented bone loss but increased hand BMD as measured by DXA.

Objective: To determine functionality and acceptability of a new teriparatide (Forteo, Eli Lilly and Company, Indianapolis, IN, USA) delivery device by patients with osteoporosis., Research Design and Methods: This was an eight week, single-arm, multicenter, open-label clinical trial. Patients received teriparatide 20 microg/day by subcutaneous injection using a new delivery device. Men and postmenopausal women with osteoporosis at high risk for fracture were stratified to Current User (n = 92) or Not Current User (n = 107) groups. Current Users had used the original delivery device for > or =8 weeks, including uninterrupted use for four weeks before enrollment., Clinical Trial Registration: ClinicalTrials.gov, NCT00577863., Main Outcome Measures: The primary objective was to detect common complaints (> or =3% for all patients) regarding the functionality and acceptability of the new device. Complaints were categorized as functional (e.g., malfunction), nonfunctional (e.g., size), or user manual. Secondary objectives included questionnaire assessment of preference of the new versus original device, features of the new delivery device, and analysis of adverse events., Results: A total of 31 patients (16%) reported 47 complaints (four functional, 27 nonfunctional, and 16 user manual). There were two common complaints: device size (4.0%) and lack of information on alcohol swabs (3.5%). Overall, patients agreed that the new device was easy to use (99.5%), easy to learn to use (99%), easy to attach a needle (97%), easy to hold while injecting (95%), and that it reduced their reluctance to take injections (90%). Most Current Users (92%) preferred the new delivery device over the original device. Adverse events reported by > or =2% of patients were upper respiratory infection (3.5%), urinary tract infection (2%), influenza (2%), and headache (2%). Limitations include the one-arm study design and the short (eight week) duration of the study., Conclusions: Patients found the new teriparatide delivery device easy to use and Current Users preferred the new delivery device over the original device.

Synovial fluid aspiration and analysis is the gold standard for making the diagnosis of gout but is not always performed when indicated in clinical practice. In clinical situations when joint aspiration simply cannot be performed, a presumptive (or clinical) diagnosis of gout may be made in consultation with published recommendations and criteria from expert societies. A thorough patient history and physical examination are critical to a presumptive diagnosis of gout, as is serum urate measurement at the time of an acute attack and at follow-up 2 weeks later.

Objective: To evaluate the immunogenicity, safety, and efficacy of 50 mg/mL liquid etanercept., Methods: In a multicenter, open-label study, adults with active rheumatoid arthritis (RA) received 50 mg/mL liquid etanercept subcutaneously once weekly for 24 weeks. Immunogenicity was assessed at baseline and weeks 24 and 28, safety at all study visits, and efficacy at baseline and weeks 12 and 24., Results: Of 222 treated patients, 88% completed the study; 81% were women; 84% were white; mean age was 53 years; mean RA duration was 10 years. Antibodies to etanercept, all non-neutralizing, were detected in 12 of 214 patients; 7 of the 12 were borderline positive (antibody titers <1:50). The presence of non-neutralizing anti-etanercept antibodies did not appear to affect clinical safety or efficacy. Few patients reported serious adverse events (6.3%), serious infections (2.3%), or withdrew because of adverse events (4.5%). Most adverse events were mild or moderate. The most common event, injection site reaction, occurred in 29.3% patients. At week 24, 63% of patients achieved an ACR20 response, 36% an ACR50 response, and 14% an ACR70 response. Similar responses were apparent by week 12. Week 24 mean improvement in the Health Assessment Questionnaire disability index scores was 0.6 points; improvement in the Short Form-36 Physical Component Score was 10.0 points., Conclusion: The 50 mg/mL liquid etanercept formulation administered once weekly was well tolerated. The incidence of anti-etanercept antibodies, the nature and frequency of adverse events, and improvements in signs and symptoms of RA and patient physical function were similar to those in previous etanercept studies.

Vertebral fractures are the most common osteoporotic fracture and may result in back pain with functional limitations and diminished quality of life. Teriparatide [rhPTH (1-34)] has been shown to increase bone mass and reduce the risk of vertebral and other osteoporotic fractures. The aim of this study was to evaluate the effects of teriparatide on the risk of back pain in patients with osteoporosis. A systematic review of the literature was performed, and five trials were identified and included in our analyses. All trials were randomized, double-blinded, and parallel with either new vertebral fracture (n=1) or bone mineral density as the primary endpoint (n=4). Four studies were in postmenopausal women with osteoporosis, and one was in men with idiopathic or hypogonadal osteoporosis. Two trials were placebo controlled, two trials were alendronate controlled, and one trial involved teriparatide plus hormone replacement therapy versus hormone replacement therapy alone. Reports of back pain, defined as new or worsened back pain after initiating the study drug, were obtained from adverse event databases, and the risk of back pain was analyzed using a multivariate Cox proportional hazards model. Results were not statistically heterogeneous (P=0.60) across trials, and there were no differences between groups administered teriparatide 20 or 40 mcg/day doses (P=0.64). The rates of back pain, moderate or severe back pain, and severe back pain per 100 patient-years were numerically lower in the teriparatide versus comparator groups in each study. Compared with the pooled comparator, patients in the pooled teriparatide group had reduced risk for any back pain [relative risk, 0.66 (95% CI, 0.55-0.80)], moderate or severe back pain [relative risk, 0.60 (95% CI, 0.48-0.75)] and severe back pain [relative risk, 0.44 (95% CI, 0.28-0.68)]. Separate meta-analyses comparing teriparatide versus placebo or antiresorptive drugs gave similar results. In conclusion, patients randomized to teriparatide had a reduced risk of new or worsening back pain compared to patients randomized to placebo, hormone replacement therapy or alendronate.

Introduction: Teriparatide [rhPTH (1-34)] reduces fracture risk, and in a published meta-analysis of clinical trials, teriparatide-treated patients had reduced incidence of back pain relative to placebo or to antiresorptive drugs. The aim of this study was to evaluate back pain in teriparatide-treated versus comparator-treated patients during an interval including controlled clinical trials plus 30 months of additional follow-up., Methods: A meta-analysis of four completed randomized, double-blinded trials of teriparatide [rhPTH (1-34)] versus comparator was performed. A multivariate Cox proportional hazards model was used to assess the heterogeneity of results and to estimate the relative risk of back pain., Results: Patients in the pooled teriparatide group had reduced risk for any back pain [relative risk, 0.73 (95% CI, 0.61-0.87)], moderate or severe back pain [0.72 (0.58-0.89)], and severe back pain [0.39 (0.25-0.61)] compared with pooled controls, from initiation of the study drug through the end of follow-up. Sensitivity analysis showed that the results were robust to the removal of each individual trial from the meta-analysis. Separate meta-analyses comparing teriparatide versus placebo or antiresorptive drugs gave similar results., Conclusions: Teriparatide-treated patients had a reduced incidence of back pain versus those receiving a comparator during an observation encompassing clinical trials plus 30 months of posttreatment observation.

Teriparatide (rDNA origin) injection [recombinant human PTH (1-34)] stimulates bone formation, increases bone mineral density (BMD), and restores bone architecture and integrity. In contrast, bisphosphonates reduce bone resorption and increase BMD. We compared the effects of teriparatide and alendronate sodium on BMD, nonvertebral fracture incidence, and bone turnover in 146 postmenopausal women with osteoporosis. Women were randomized to either once-daily sc injections of teriparatide 40 micro g plus oral placebo (n = 73) or oral alendronate 10 mg plus placebo injection (n = 73). Median duration of treatment was 14 months. At 3 months, teriparatide increased lumbar spine BMD significantly more than did alendronate (P < 0.001). Lumbar spine-BMD increased by 12.2% in the teriparatide group and 5.6% in the alendronate group (P < 0.001 teriparatide vs. alendronate). Teriparatide increased femoral neck BMD and total body bone mineral significantly more than did alendronate, but BMD at the one third distal radius decreased, compared with alendronate (P < or = 0.05). Nonvertebral fracture incidence was significantly lower in the teriparatide group than in the alendronate group (P < 0.05). Both treatments were well tolerated despite transient mild asymptomatic hypercalcemia with teriparatide treatment. In conclusion, teriparatide, a bone formation agent, increased BMD at most sites and decreased nonvertebral fractures more than alendronate.

Background: Cevimeline hydrochloride is a cholinergic agent with muscarinic agonist activity prominently affecting the M1 and M3 receptors prevalent in exocrine glands. We evaluated the safety and efficacy of cevimeline in the treatment of xerostomia in patients with Sjögren syndrome., Methods: Seventy-five patients with Sjögren syndrome and associated salivary gland dysfunction were enrolled in a double-blind, randomized, placebo-controlled trial at 8 university- and office-based outpatient clinical facilities in the United States. Eligible study participants were randomized to receive 30 mg of cevimeline 3 times daily, 60 mg of cevimeline 3 times daily, or placebo for 6 weeks. Subjective responses were determined using global patient evaluation and visual analog scales. Salivary flow was measured objectively., Results: Sixty-one participants completed the study. Patients in both cevimeline groups had significant improvements in dry mouth, as indicated by symptoms, salivary flow, and use of artificial saliva, compared with the placebo group. The drug was generally well tolerated, with expected adverse events resulting from the drug's muscarinic agonist action. Fourteen patients withdrew from the study because of adverse events, the most frequent being nausea., Conclusions: Therapy with cevimeline, 30 mg 3 times daily, seems to be well tolerated and to provide substantive relief of xerostomia symptoms. Although both dosages of cevimeline provided symptomatic improvement, 60 mg 3 times daily was associated with an increase in the occurrence of adverse events, particularly gastrointestinal tract disorders. Use of 30 mg of cevimeline provides a new option for the treatment of xerostomia in Sjögren syndrome.

The distinctions between eosinophilic fascitis (Shulman's syndrome) and scleroderma may sometimes be unclear. We describe a patient with generalized morphea who also had peripheral blood eosinophilia, fibrosis and inflammation of fascia, and hyper-globulinemia, features usually attributed to Shulman's syndrome. The latter diagnosis should be restricted to those patients whose history, clinical and laboratory findings, and response to therapy closely resemble Shulman's original description. Scleroderma and eosinophilic fasciitis may represent slightly differing aspects of the same disease spectrum, with a similar immunologic pathogenesis.