Inflammatory myopathies are a heterogeneous group of systemic autoimmune disorders with highly variable clinical presentations. The limited number of clinical trials has hindered the development of strong evidence-based management strategies. Therefore, there is a pressing need for consensus-driven treatment guidelines tailored to the various clinical and immunological phenotypes. This review combines existing published guidelines with the authors’ clinical experience to provide a comprehensive, pragmatic approach to management. A comparative review of existing treatment guidelines was recently published, revealing significant heterogeneity in therapeutic approaches and recommendations. This observation is consistent with our own experience during a multidisciplinary meeting, primarily involving internal medicine specialists and rheumatologists. Furthermore, recent clinical trials and observational studies investigating novel therapies offer promising prospects that could influence future clinical decision-making. Although establishing a unified therapeutic algorithm remains challenging, this review aims to translate current knowledge into clinical practice by integrating existing guidelines, our own clinical experience, and the most recent evidence published on the topic.
This review aims to evaluate current treatment approaches for sporadic late-onset nemaline myopathy (SLONM) and explore how emerging omics data, particularly proteomics and transcriptomics, can contribute and optimize therapeutic strategies. SLONM presents with clinical and pathological variability and is frequently associated with monoclonal gammopathy of undetermined significance (MGUS), which can influence both disease progression and response to treatment. Standard therapies include immunosuppressive agents, intravenous immunoglobulin (IVIG), chemotherapy, and autologous stem cell transplantation (ASCT), with ASCT showing particularly favorable outcomes in MGUS-associated cases. Recent proteomic studies have identified distinct molecular patterns in SLONM, including altered expression of sarcomeric and immune-related proteins, as well as deposits of immunoglobulin light chains. Complementary transcriptomic data highlight immune dysregulation and metabolic stress as key contributors to disease pathology. Together, these findings support the development of omics-informed precision therapies that target plasma cell clones and immune pathways, offering improved patient stratification and more tailored treatment approaches. Integrating omics data with clinical features deepens our understanding of SLONM pathogenesis and helps explain the variability in treatment responses. Targeted therapies—especially plasma cell-directed approaches in MGUS-positive patients and immunomodulatory strategies in MGUS-negative cases—are showing encouraging results. Future research should focus on validating omics-based biomarkers to refine diagnosis and support the development of personalized treatment protocols, ultimately improving outcomes in this rare but treatable muscle disorder.
Patients with autoimmune rheumatic diseases (ARDs) and active malignancy pose a unique therapeutic dilemma: controlling autoimmune disease while preserving tumor immune surveillance. This review synthesizes existing evidence, identifies knowledge gaps, and proposes practical considerations for co-management. Emerging studies suggest conventional synthetic and biologic DMARDs, particularly TNF inhibitors, may be safer than previously assumed in patients with cancer, with limited evidence of increased recurrence risk. Some therapies, including abatacept and JAK inhibitors, warrant caution due to potential malignancy signals. Immune checkpoint inhibitors (ICIs) frequently trigger autoimmune flares; however, most are manageable with corticosteroids or DMARDs, and ICI therapy can often continue. Data on concurrent chemotherapy or radiation remain sparse, and treatment decisions require individualized assessment of cancer type, prognosis, and autoimmune disease activity. Overall, shared decision-making integrating rheumatology and oncology perspectives is essential. While TNF inhibitors remain the preferred biologics when needed, therapy should be tailored to cancer stage, autoimmune disease severity, and patient values. Prospective studies are urgently needed to guide immunomodulatory therapy use in this complex, high-risk population.
In the last ten years, many clinical trials evaluating the efficacy of targeted therapies in polymyalgia rheumatica (PMR) have been published. Knowledge in this field is evolving very rapidly and a review of the current evidence available will help physician to follow these many innovations. The interleulin-6 receptor inhibitors – tocilizumab and sarilumab – have been evaluated in several randomized controlled trials. The results are consistent and demonstrate an efficacy of these drugs in early PMR and in relapsing or in glucocorticoid-dependent PMR. Among the therapies targeting lymphocytes, rituximab was efficient in decreasing the PMR-AS and preventing the use of long-term glucocorticoids. On the other hand, abatacept was not proven efficient in early PMR. The other promising drugs are baricitinib and secukinumab. Baricitinib was superior to placebo in a small randomized controlled trial. Secukinumab was Mainly studied in giant cell arteritis, but an international phase 3 trial is ongoing in PMR. In the last national recommendations for the management of PMR published (in France and in Norway), the use of targeted therapies (tocilizumab and sarilumab) has been incorporated in early disease or in relapsing disease.
There is a strong need for tools to monitor disease activity and identify prognostic markers to ensure optimal treatment efficacy in giant cell arteritis (GCA). Vascular ultrasonography (US) is widely implemented in clinical practice to establish diagnosis, and ongoing research continues to investigate its broader utility in GCA. In this review, we explore the role of US in disease activity monitoring and as a prognostic marker. US scoring systems reflecting the extent and severity of vascular inflammation, such as the OMERACT Ultrasonography GCA Score (OGUS), halo count and Southend Halo Score have shown sensitive to change. Positive US findings and worsening in these scores have been reported at relapse. Recent studies indicate that OGUS can predict relapse and the need for glucocorticoid sparing treatment. Sensitivity to change of US is well-supported by the literature but the discriminative and prognostic value of US is not well established. Further studies are needed to define an US relapse, including the degree of vessel wall thickening, the rate at which it develops in parallel to clinical activity, and whether US provides added value in clinical practice. Additional prospective studies are warranted to confirm and evaluate recent prognostic findings of US.
To summarize current approaches to the evaluation and treatment of fatigue in patients with systemic, autoimmune rheumatic diseases (SARD). The mechanisms of fatigue in SARD include both disease-related (peripheral) and individual general health (central) factors and both need to be measured and understood. Fibromyalgia is the most important co-morbidity to account for persistent fatigue in the SARD. Pain and fatigue are closely aligned.The discordance between fatigue measures and disease activity is explained by central, rather than peripheral mechanisms. When targeted pharmacologic treatment achieves disease remission, residual significant fatigue and pain need to be treated with individualized, biopsychosocial management.
New advances in the treatments of autoimmune rheumatic diseases have altered the landscape of opportunistic infection risk, including infections such as herpes zoster, tuberculosis and pneumocystis jirovecii pneumonia. Recommendations for preventative strategies, including vaccination and prophylaxis, have also evolved in response to availability of new vaccines and decreased reliance on glucocorticoid therapy. The newest treatment options, including Janus Kinase (JAK) inhibitors and the type 1 interferon receptor inhibitor, anifrolumab, have been associated with an increased risk of herpes zoster compared to other existing immunosuppressive agents in rheumatology, beyond the already high baseline risk. The adjuvanted zoster virus has allowed safe immunization of rheumatology patients in attempt to reduce the incidence of herpes zoster albeit with recent population based studies demonstrating less effectiveness than in immunocompetent patients. Infection risk assessment requires stratification of host, disease and treatment factors. Despite advances in immunosuppressive therapy, glucocorticoid use is still substantial and contributes to risk of opportunistic infections. Introduction of Shingrix, a non-live vaccine has made immunization for HZ more straight forward for immunocompromised patients. It is important to assess risk for other opportunistic infections, like pneumocystis jirovecii and tuberculosis, and prescribe prophylaxis.
To evaluate how myositis-specific and -associated autoantibody profiles inform prognosis and guide therapeutic decision-making in idiopathic inflammatory myopathies (IIMs). By synthesizing recent cohort studies, meta-analyses, and clinical trials, this review aims to establish a practical, serology-driven framework for individualizing treatment—ranging from corticosteroids and conventional immunosuppressants to targeted biologics, intravenous immunoglobulin, and emerging modalities such as JAK inhibitors and CAR-T cell therapy. Distinct autoantibody endotypes exhibit predictable organ involvement, malignancy risk, and treatment responsiveness. Anti-Mi-2 dermatomyositis demonstrates robust steroid sensitivity and low incidence of cancer, whereas anti-TIF1-γ and anti-NXP2 require intensive oncologic surveillance due to a heightened risk of neoplasia. Anti-MDA5 positivity presents with rapidly progressive interstitial lung disease best managed with upfront combination immunosuppression and JAK inhibitors. Immune-mediated necrotizing myopathies (anti-SRP, anti-HMGCR) benefit from IVIG and or early B-cell depletion, and anti-synthetase syndrome responses are enhanced by rituximab in refractory interstitial lung disease. Preliminary data support the use of interferon pathway blockade in cutaneous dermatomyositis and CAR-T therapy for refractory necrotizing myopathy. Incorporating autoantibody profiling into routine evaluation enables targeted surveillance and timely escalation to biologics or novel therapies, reducing morbidity and mortality. A serology-guided algorithm optimizes immunosuppressive regimens, cancer screening, and supportive measures, thereby advancing precision medicine in IIM management.
Obesity is associated with elevated cardiovascular risk, greater pain, and higher disease activity/severity in several rheumatic diseases. Intentional weight loss through dietary or surgical interventions has been shown to improve pain and disease control in common arthritides like osteoarthritis (OA), rheumatoid arthritis (RA), and psoriatic arthritis. In this review, we summarize FDA-approved and off-label medications for weight loss, highlighting practical considerations and potential pleiotropic benefits for people with rheumatic diseases. Preclinical studies suggest immunomodulatory, chondroprotective, and analgesic properties of both glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and metformin, highlighting potential for these agents in rheumatology. Randomized controlled trials (RCTs) and large cohort studies have found that GLP-1 RAs and metformin improve pain in OA and may prevent progression to joint replacement. Large population-based cohort studies and secondary analyses of RCTs suggest that sodium-glucose cotransporter-2 inhibitors (SGLT2is) likely lower risk of gout attacks. While limited, emerging clinical data on GLP-1 RAs, metformin, and SGLT2is in other rheumatic diseases are promising. Medications that facilitate weight loss may benefit people with rheumatic diseases and excess adiposity through various mechanisms. Further clinical research is needed. Carefully reviewing a patient’s history is crucial to ensure appropriate medication selection to maximize potential benefit and minimize risk.
Systemic sclerosis (SSc) is a rare, complex autoimmune connective tissue disease with significant morbidity and mortality. Management of SSc has centered on organ-specific manifestations; and recent advances have furthered our understanding of pathophysiology, uncovered new therapeutic targets, and increased drugs available. Despite this, several recent negative clinical trials have dampened enthusiasm for further investigation of potentially beneficial therapies in systemic sclerosis. Outcome measurements are often sensitive to change but benefit with some treatments is very low so trials may be underpowered to determine efficacy. Additionally, the more common subset of SSc is limited cutaneous SSc and overall disease modification in this group has not been subjected to randomized trials except if there is specific organ involvement. New articles have discussed improving upon trial design in SSc in order to reduce care gaps (such as having RCTs in prevalent patients with active SSc and the more common lcSSc subset). There have been publications on improving the sensitivity and developing outcome measurements, using pragmatic or basket trial designs, eliminating placebo arms, and increasing inclusion of diverse patients and various subsets of SSc; all of which can reduce SSc unmet needs. We propose that a paradigm shift is needed to revolutionize clinical trials in systemic sclerosis and discuss innovative approaches to clinical trial design that will help transform the research landscape.
Gout flares are sudden, intensely painful inflammatory episodes triggered by the accumulation of monosodium urate crystals in the joints. Management aims to reduce inflammation and relieve pain, with non-steroidal anti-inflammatory agents (NSAIDs), corticosteroids, and colchicine used as first line treatment options. Since these therapies have shown similar efficacy, the choice among them depends on individual patient factors such as comorbid conditions, medication interactions, drug availability, and potential side effects. In cases where standard treatments are non-effective or contraindicated, newer alternatives including IL-1β inhibitors or dapansutride are increasingly being studied. This review will discuss current approaches to gout flare management, with particular focus on different clinical scenarios where gout coexists with comorbidities including chronic kidney disease, cardiovascular disease, diabetes, and infection.
Giant cell arteritis (GCA) is characterized by chronic vascular inflammation and pathological remodeling. While current therapies primarily rely on broad immunosuppression by glucocorticoids, they fail to halt pathologic remodeling and heal the arteries. Fibroblasts are highly plastic cells that may present the link between chronic inflammation and pathological remodeling. This narrative review aims to give an overview of the possible therapeutic strategies targeting fibroblasts in GCA. Recent studies have identified and mapped the distribution of various fibroblast subtypes in arteries affected by GCA, highlighting their potential role in both the chronicity of vascular inflammation and pathological remodeling. Advances in molecular tools such as (spatial) transcriptomics and proteomics, along with in vitro models enhance our understanding of the role of fibroblasts in the pathogenesis of GCA and help to identify new fibroblast-related pathways amenable for therapeutic intervention. Evidence for an effect of pharmacological agents currently used to treat GCA, like glucocorticoids, methotrexate, leflunomide and the interleukin-6 receptor blocker tocilizumab on vascular fibroblasts is limited. New targeted therapies recently approved for GCA, such as the JAK-STAT inhibitor upadacitinib, or other drugs recently or currently being tested in clinical trials offer new opportunities for modulation of vascular fibroblasts in GCA. Depletion of specific pathological fibroblast subtypes or modulation of fibroblast differentiation towards reparative of homeostatic phenotypes, combined with targeted immunosuppression may contribute to vascular healing in GCA.
Glucocorticoid (GC) toxicity is a major concern in the management of giant cell arteritis (GCA). Tocilizumab (TCZ) has been introduced as a GC-sparing agent in GCA. This review critically analyses the extent of the GC-sparing capacity of TCZ and explores its impact on molecular and imaging findings. Two randomized controlled trials investigated the GC-sparing potential of TCZ in the treatment of GCA. Four Proof-of-concept studies have investigated the extent to which GC exposure can be further minimized. Recent evidence highlights the chronicity of GCA, emphasizing the need for low-toxicity treatment strategies and advocating for long-term follow-up. Reducing GC toxicity is one of the most important trends in the management of GCA. New treatment strategies include TCZ and reducing GC exposure and toxicity in patients diagnosed with GCA.
Diffuse idiopathic skeletal hyperostosis (DISH) is a noninflammatory condition associated with the ossification and calcification of spinal ligaments and peripheral entheses. Management of mild symptoms is often conservative, though surgical intervention has been implicated for patients with debilitating symptoms. This literature review aims to review current management concepts of patients with DISH, including both conservative and surgical treatment options. Studies utilizing conservative treatment included pharmacotherapy, physical therapy, orthosis immobilization, or chiropractor manipulation. Conservative management of DISH is often performed for patients who do not have unstable spine fractures or neurological deficits. Orthosis immobilization and physical therapy have been found to improve symptoms associated with DISH (back pain, stiffness); however, brace compliance is reported to be a strong predictor of clinical outcomes. For patients with symptoms refractory to conservative treatment or presented with airway compromise or neurological deficits, surgical management can yield good outcomes. Several studies have reported improvement in dysphagia and dyspnea following resection of cervical osteophytes in patients with DISH. Although the primary treatment for DISH is typically nonoperative, surgical intervention can provide effective treatment that results in favorable outcomes. Surgery may be recommended for patients who fail to recover after conservative management or for patients with unstable spine fractures complicated by neurological deficits, respiratory symptoms, or dysphagia.
This review aims to summarize the landscape of therapies that are currently being tested or planned in patients with idiopathic inflammatory myopathies (IIM), emphasizing a variety of clinical trials focused on mitigating the progression of these conditions. Novel therapies for IIM are evolving, with recent studies highlighting several promising approaches. This shift will outline the advancements achieved thus far in the treatment of IIM.
This review aims to clarify the different definitions and contexts of the term "early" in systemic sclerosis (SSc) and its implications in clinical practice and research. The term "early" has been used inconsistently, leading to confusion in diagnosing, managing, and conducting research on SSc. Recent studies have explored the evolution of patients from very early SSc stages to established disease. The development of the Very Early Diagnosis of Systemic Sclerosis (VEDOSS) criteria has marked a significant step forward. However, studies have shown varying progression rates among patients meeting different "early" criteria, with a subset remaining in mild or indolent stages for extended periods. Significant gaps remain in predicting disease progression, prompting the need for more refined and personalized criteria. Systemic sclerosis is a complex disease with high morbidity and mortality. The inconsistent use of the term "early" has led to challenges in diagnosis, treatment, and research. While the VEDOSS criteria have provided a framework for identifying very early SSc, further refinement is needed to improve disease progression predictions. A more personalized approach to patient monitoring and the application of adjusted VEDOSS criteria may enhance early intervention strategies, ultimately aiming to prevent disease progression in SSc.
The increase in available treatments has resulted in a significant improvement in the management of autoimmune rheumatic diseases (ARDs). Despite improvements in disease-specific outcomes, the diseases and their treatments can predispose to long-term risks of metabolic dysfunction including higher rates of sarcopenia and metabolic obesity. Higher rates of cardiovascular, metabolic, and other complications have been recognized over time, though mechanistic pathways that link ARDs, metabolic obesity, muscle loss, and adverse long-term outcomes remain inadequately characterized. In this review, we aim to overview recent research evaluating interplay between inflammation, immunomodulatory treatments, adiposity, and sarcopenia as well as the impact on clinical outcomes. Recent studies continue to explore the relationship between ARDs, body composition, and cardiometabolic outcomes. Recent work has also highlighted clinical associations with adipo(cyto)kines, circulating signaling proteins that play a role in energy homeostasis. However, much work remains to characterize the causal role of these proteins in the context of ARDs. While some studies have shown a potential metabolic benefit to pharmacologic therapies for ARD, more work is needed, particularly in less common ARDs. Inflammation in the context of ARDs is linked to metabolic changes including metabolic obesity and sarcopenia. While treatment of the underlying conditions may have metabolic benefits, some treatments increase metabolic risk. Further study is needed to better inform management, particularly with advent of effective therapies for weight loss.
Systemic sclerosis (SSc) is a multisystem autoimmune disease characterised by the presence of fibrosis, microvasculopathy and inflammation. The complex pathogenesis and widespread organ involvement have made assessment and quantification of overall disease activity challenging. In this review, we present an update of the assessment of disease activity in SSc. There has been increasing interest in the use of composite outcome measures to assess the totality of SSc and measure multidimensional disease constructs such as activity and damage. Recently, the Scleroderma Clinical Trials Consortium (SCTC) published a new SSc Activity Index (SCTC-AI) to quantify disease activity across nine domains of disease. In this article, we discuss both the challenges of measuring disease activity in SSc and the rationale and clinical importance of accurate quantification of disease activity. Heterogeneity in clinical presentation, variation in the tempo of disease and variable responsiveness to treatment at different disease stages has resulted in significant challenges in classification and assessment of SSc patients. However, two SSc-specific activity indices now exist to quantify states of high disease activity. Further work is required to establish whether composite outcome measures offer superior measures of treatment response in SSc clinical trials and what the role of the assessment of disease activity is in the recruitment and assessment of participants in trials of novel therapies.
Eosinophilic fasciitis (EF) is a rare inflammatory disease characterized by skin induration. Although some guidelines from scientific societies exist, standard recommendations on monitoring and therapy are lacking. Current therapy for patients diagnosed with EF includes glucocorticoids plus at least one immunosuppressive drug in cases of relapse or refractory disease. Methotrexate and mycophenolate mofetil are the most recommended, although recently a myriad of case reports or small series reporting the effectivity of biological agents or JAK inhibitors for treating relapses or refractory disease have been published. Anti-IL5 may have a role in those rare refractory cases with persistent eosinophilia. Intravenous immunoglobulins and photopheresis (in those centers with experience) may act as adjuvant therapies. Monitoring the disease activity is a cornerstone to ascertain if the treatment is useful or not. MRI, PET/TC, and more specifically POCUS have recently demonstrated their value for assessing therapy response. High-quality data focused on therapy and monitoring is lacking in EF. Strategies for improving scientific quality of observational studies and consensus about “activity”, “sequela”, “relapse” or “refractoriness” terms in EF patients are necessary to implement prospective clinical trials and generate evidence-based medicine. Meanwhile we have to deal with the available information.
Systemic sclerosis (SSc) is a rare immune-mediated connective tissue disease with high morbidity and mortality. Interstitial lung disease (ILD) is now the leading cause of death for patients with SSc. While several therapeutic agents have been approved for SSc-ILD, opportunities remain for a personalized medicine approach to improve patient outcomes. The purpose of this narrative review is to summarize the current state of personalized medicine for SSc-ILD and future directions to facilitate earlier diagnosis, disease stratification, prognostication, and determination of treatment response. We also review opportunities for personalized medicine approaches within clinical trial design for SSc-ILD. The management of SSc-ILD remains challenging due to its variable clinical course and current deficits in predicting which individuals will develop progressive pulmonary fibrosis. There have additionally been many challenges in clinical trial design due to limitations in enrichment strategies. Emerging data suggest that serum, radiologic, and other novel biomarkers could be utilized to assess disease activity and treatment response on an individual level. Personalized medicine is emerging as a way to address unmet challenges in SSc-ILD and has applicability for identifying stratifying, prognostic, and therapeutic markers for routine clinical care and clinical trial design.
