Guidelines or diagnostic criteria in clinical practice assist physicians in their clinical decision-making and improve health outcomes for patients. Diagnostic and classification criteria should be ...based on evidence from rigorously conducted controlled studies. Formal group consensus methods have been developed to organize subjective judgments and to synthesize them with the available evidence. This review discusses 4 types of formal consensus methods used in the health field and their applications in rheumatology: the Delphi method, Nominal Group Technique, RAND/UCLA Appropriateness Method, and National Institutes of Health consensus development conference.
The antifibrotic therapies nintedanib and pirfenidone were first approved by the United States for the treatment of idiopathic pulmonary fibrosis in 2014. In 2020, nintedanib received U.S. Food and ...Drug Administration (FDA) approval for the treatment of all progressive fibrosing interstitial lung disease (ILD). Given that a major cause of mortality and morbidity in the idiopathic inflammatory myopathies (IIM) is progressive interstitial lung disease and respiratory failure, antifibrotic therapies may be useful as adjuvant to traditional immunosuppression. However, randomized controlled trials of antifibrotic therapies in IIM are lacking. The purpose of this review is to (1) summarize the mechanism of action of nintedanib and pirfenidone in ILD with possible role in IIM-ILD, (2) review the clinical data supporting their use in interstitial lung disease in general, and more specifically in connective tissue disease associated ILD, and (3) discuss the evidence and remaining challenges for using antifibrotic therapies in IIM-ILD.
How to manage a patient who has an elevated serum creatine kinase (CK) level but no or insignificant muscle-related signs and symptoms is a clinical conundrum. The authors provide a systematic ...approach, including repeat testing after a period of rest, defining higher thresholds over which pursuing a diagnosis is worthwhile, and evaluating for a variety of nonneuromuscular causes. They also outline a workup for neuromuscular causes.
The Idiopathic Inflammatory Myositis (IIM) are heterogenous with distinct clinical phenotypes associated with specific myositis specific antibodies (MSA) and myositis associated antibodies (MAA).
To ...evaluate the frequency, pattern and associations of MSA/MAA in a large Indian cohort of IIM.
Adult and juvenile IIM (2017 ACR/EULAR criteria), were recruited in the MyoCite cohort between 2017and 2020 at a tertiary center in Northern India. Standardized clinical and laboratory variables were extracted from the database archive. Serum samples were evaluated for the presence of MSAs/MAAs by Line immunoassay and anti-nuclear antibodies (ANA) by Immunofluorescence assay (IFA). The prevalence and clinical associations of different MSA/MAAs were assessed.
MSA and MAAs were tested in 250 IIM patients (214 adults, 36 children) of age 40 (30–49), 13 (7.5–16) years and disease duration 7 (3–17), 6 (2–17) months comprising predominantly of Dermatomyositis (DM) followed by Overlap myositis (OM). MSAs/MAAs were found in 148 (59.2%, 60.7% adults and 50% JIIM), of which two-thirds were MSA (95, 64% overall). Two cases (0.8%) had more than one MSA. In adult IIM, the most common MSA was anti-Jo-1 (10%), whereas it was anti-MDA5 and anti-NXP2 4 (11%) each in Juvenile IIM (JIIM). 76.0% (172/226) were ANA positive, with speckled pattern being the most common (37%,). Nearly two-thirds (54, 61%) of those with negative ANA had MSA/ MAA. Nearly half (18/54, 54.6%) had MSA associated with cytoplasmic patterns. ARS (anti-aminoacyl-tRNA synthetase) were associated with mechanic's hands (OR-7.06), ILD (OR-4.4), and arthritis (OR-2.23). Clinical associations of anti-Jo-1 and non-Jo-1 Anti synthetase syndrome (ASS) did not differ. Anti-MDA-5 associated with oral ulcers (OR-8.3), fever (OR-8.6) and weight loss (OR-7.35) in adults, and arthritis (OR-11.5), and periungual rash (OR-9.6) in children. Anti-TIF-1γ associated with photosensitivity (OR-10.44) and malignancy (OR-34) in adults, and cuticular overgrowth (OR-11.2) in children.
Myositis autoantibodies are seen in two-thirds IIMs and are associated with distinct clinical subsets. Jo-1 and non-Jo-1 ASS exhibit similar characteristics. The association of anti-TIF1 γ with malignancy was confirmed in adults. MSA/MAA were present in two-thirds of those with negative ANA and MSA were nearly always mutually exclusive.
Currently, there are no proven drugs that are FDA approved for the treatment of dermatomyositis (DM), even though multiple clinical trials are ongoing to evaluate safety and efficacy of novel ...therapeutics in DM. The purpose of this review is to highlight the biological plausibility, existing clinical evidence as well as completed and ongoing clinical trials for various drugs in pipeline for development for use in dermatomyositis.
The drugs with the strongest evidence have been included in this review with a focus on the mechanism of their action pertaining to the disease process, clinical studies including completed and ongoing trials. With better understanding of the underlying pathophysiologic process, there are new molecular targets that have been identified that can be targeted by these novel drugs, predominantly biologic drugs.
There are various drugs being evaluated in phase II/III clinical trials that hold promise in DM. At the forefront of these are immunoglobulin, Lenabasum, and Abatacept for which phase III clinical trials are ongoing. In addition, promising clinical studies are ongoing or reported for KZR-616, anti-B cell therapy, anti-interferon drugs, and Repository Corticotrophin Injection (RCI).
The Pfizer-BioNTech COVID-19 vaccine has been authorized by the U.S. Food and Drug Administration as it demonstrated 95% effectiveness against the SARS-CoV-2 virus. Although the initial vaccine ...trials showed a favorable side effect profile, there have been concerns regarding activation of aberrant immune responses, triggering autoimmunity. This is a case report of a 68-year-old woman without history of autoimmune conditions, who presented to our emergency department 7 days after receiving the Pfizer-BioNTech COVID-19 vaccine. Her initial symptoms were suggestive of polymyalgia rheumatica, and she had nearly complete response to steroids. Interestingly, she later met criteria for classified systemic lupus erythematous given the development of inflammatory arthritis, positive ANA, and positive dsDNA. The temporal relationship of her symptoms that started 2 days after vaccine administration could suggest a possible association between the Pfizer-BioNTech COVID-19 and the development of systemic lupus erythematous.
The discovery of novel autoantibodies related to idiopathic inflammatory myopathies (collectively referred to as myositis) has not only advanced our understanding of the clinical, serological, and ...pathological correlation in the disease spectrum but also played a role in guiding management and prognosis. One group of the myositis-specific autoantibodies is anti-aminoacyl-tRNA synthetase (anti-ARS or anti-synthetase) which defines a syndrome with predominant interstitial lung disease, arthritis, and myositis. Autoantibodies to eight aminoacyl-tRNA synthetases have been identified with anti-Jo1 the most common in all of idiopathic inflammatory myopathies. Disease presentation and prognosis vary depending on which anti-aminoacyl-tRNA synthetase antibody is present. In this review, we will discuss the clinical characteristics, overlap features with other autoimmune diseases, prognostic factors, and management of the antisynthetase syndrome.
We consider the problem of simultaneous user-scheduling, power-allocation, and rate-selection in an orthogonal frequency division multiple access (OFDMA) downlink, with the goal of maximizing ...expected sum-utility under a sum-power constraint. In doing so, we consider a family of generic goodput-based utilities that facilitate, e.g., throughput-based pricing, quality-of-service enforcement, and/or the treatment of practical modulation-and-coding schemes (MCS). Since perfect knowledge of channel state information (CSI) may be difficult to maintain at the base-station, especially when the number of users and/or subchannels is large, we consider scheduling and resource allocation under imperfect CSI, where the channel state is described by a generic probability distribution. First, we consider the "continuous" case where multiple users and/or code rates can time-share a single OFDMA subchannel and time slot. This yields a nonconvex optimization problem that we convert into a convex optimization problem and solve exactly using a dual optimization approach. Second, we consider the "discrete" case where only a single user and code rate is allowed per OFDMA subchannel per time slot. For the mixed-integer optimization problem that arises, we discuss the connections it has with the continuous case and show that it can solved exactly in some situations. For the other situations, we present a bound on the optimality gap. For both cases, we provide algorithmic implementations of the obtained solution. Finally, we study, numerically, the performance of the proposed algorithms under various degrees of CSI uncertainty, utilities, and OFDMA system configurations. In addition, we demonstrate advantages relative to existing state-of-the-art algorithms.
Interstitial lung disease (ILD) is common in connective tissue disease (CTD) and is the leading cause of mortality. Investigators have used certain outcome measures in randomized controlled trials ...(RCT) in CTD-ILD, but the lack of a systematically developed, CTD-specific index that captures all measures relevant and meaningful to patients with CTD-ILD has left a large and conspicuous gap in CTD-ILD research.
The CTD-ILD working group, under the aegis of the Outcome Measures in Rheumatology (OMERACT) initiative, has completed a consensus group exercise to reach harmony on core domains and items for inclusion in RCT in CTD-ILD. During the OMERACT 12 meeting, consensus was sought on domains and core items for inclusion in RCT. In addition, consensus was pursued on a definition of response in RCT. Consensus was defined as ≥ 75% agreement among the participants.
OMERACT 12 participants endorsed the domains with minimal modifications. Clinically meaningful progression for CTD-ILD was proposed as ≥ 10% relative decline in forced vital capacity (FVC) or ≥ 5% to < 10% relative decline in FVC and ≥ 15% relative decline in DLCO.
There is consensus on domains for inclusion in RCT in CTD-ILD and on a definition of clinically meaningful progression. Data-driven approaches to validate these results in different cohorts and RCT are needed.
PDF
