Rheumatology

Introducing Our Free WhatsApp Channels for Daily Internal Medicine Articles!

28 Jan, 2025 | 00:54h | UTC

We’re pleased to share our new WhatsApp channels, designed to provide daily articles in Internal Medicine. Whether you’re a busy healthcare professional or an enthusiast keen to stay updated on the latest research, these channels might be just what you need.

Why Join Our WhatsApp Channels?

Concise Summaries, Straight to Your Phone: Each morning, you’ll receive a brief overview of a noteworthy Internal Medicine article.
LinksMedicus Summary: Looking for more detail? Click the link to explore an extended write-up on LinksMedicus.com.
Original Source Links: We also include direct links to the original research, so you can review the full study at your own pace.

How to Join

English Channel: https://whatsapp.com/channel/0029VaxRVTvGOj9kZMybGu1X
Portuguese Channel: https://whatsapp.com/channel/0029Vawz6PF72WToJZS5It31

Simply choose your preferred language, and you’ll be all set to receive our Internal Medicine Article of the Day.

Follow Us on Twitter (X) Too!

For those who prefer social media updates, follow our official account on Twitter (X):
@Links_Medicus

We’ll share the same daily article summaries there, ensuring you can stay informed wherever you are.

RCT: Infrequent Zoledronate Infusions Reduce Vertebral Fractures in Early Postmenopausal Women Without Osteoporosis

18 Jan, 2025 | 16:48h | UTC

Background: Osteoporosis prevention typically targets older, higher-risk populations with significantly reduced bone mineral density (BMD). However, many fragility fractures occur in women who do not meet the traditional diagnostic threshold for osteoporosis (T score ≤ –2.5). This study investigated whether infrequent administration of zoledronate could prevent vertebral fractures in early postmenopausal women (50 to 60 years of age) who have BMD values between normal and osteoporotic ranges.

Objective: To determine if administering intravenous zoledronate once at baseline—and again 5 years later—could reduce the incidence of morphometric vertebral fractures and other fracture types over a 10-year period in early postmenopausal women without osteoporosis.

Methods:

Design: A 10-year, prospective, double-blind, randomized, placebo-controlled trial.
Population: 1054 women (mean age 56.0) within 10 years post-menopause, with lumbar spine or hip T scores <0 but >–2.5, recruited from the electoral roll in Auckland, New Zealand.
Interventions: Participants were randomly assigned (1:1:1) to receive:
1. Zoledronate 5 mg at baseline and again at Year 5 (zoledronate–zoledronate)
2. Zoledronate 5 mg at baseline and placebo at Year 5 (zoledronate–placebo)
3. Placebo infusions at baseline and Year 5 (placebo–placebo)
Follow-up: 10 years, with repeated BMD and spine X-ray assessments at baseline, Year 5, and Year 10.
Primary Endpoint: Incidence of new morphometric vertebral fractures, defined by semiquantitative radiographic methods.
Secondary Endpoints: Fragility fracture, any fracture, major osteoporotic fracture, changes in BMD, and bone-turnover markers.

Results:

Vertebral Fractures: Over 10 years, 6.3% of participants in the zoledronate–zoledronate group and 6.6% in the zoledronate–placebo group experienced a new morphometric vertebral fracture, versus 11.1% in placebo–placebo. After imputation, the relative risks versus placebo–placebo were 0.56 (95% CI, 0.34–0.92; p=0.04) and 0.59 (95% CI, 0.36–0.97; p=0.08), respectively.
Other Fractures: The zoledronate–zoledronate group had a 30% reduced risk of any fracture (RR, 0.70; 95% CI, 0.56–0.88), and zoledronate–placebo showed a 23% reduction (RR, 0.77; 95% CI, 0.62–0.97), both compared with placebo–placebo.
Bone Mineral Density: At Year 10, the zoledronate–zoledronate group had sustained BMD gains (~7–9 percentage points above placebo), whereas the zoledronate–placebo group retained a moderate advantage (~5–6 percentage points above placebo).
Bone-Turnover Markers: Markers remained suppressed in the zoledronate–zoledronate group through Year 10, while in the zoledronate–placebo group, they gradually rose after Year 5 but stayed below baseline levels.
Safety: Few adverse events were reported. Uveitis or episcleritis after the first infusion occurred in 1.1% of zoledronate recipients. No cases of osteonecrosis of the jaw or atypical femoral fractures were observed.

Conclusions: A single 5-mg dose of zoledronate, with an optional additional dose at five years, reduced the incidence of morphometric vertebral fractures and helped preserve BMD in younger postmenopausal women without osteoporosis. Both zoledronate regimens showed notable fracture-risk reductions and sustained effects on bone turnover.

Implications for Practice: These findings extend the potential role of zoledronate in fracture prevention to younger, early postmenopausal women without osteoporosis. Infrequent infusions are attractive because of their prolonged pharmacologic action and generally favorable safety profile. However, caution is warranted before broadly implementing this strategy for all postmenopausal women, as the data come from a relatively homogenous population and do not address other risk factors or comorbidities. Real-world adherence, healthcare resource allocation, and patient preferences must all be considered. Moreover, further evaluation of cost-effectiveness is essential, especially if expanding use to large populations. Longer follow-up in broader and more diverse groups may reveal less common adverse events that were not detected in this trial. Clinicians should therefore weigh individual risk–benefit profiles and await additional data before making universal recommendations.

Study Strengths and Limitations:

Strengths: The trial’s 10-year duration, double-blind design, and high retention rate enhance its internal validity. Using radiographic assessments for vertebral fractures adds objectivity and robustness.
Limitations: The trial predominantly involved healthy, early postmenopausal women of European descent, limiting the applicability of the findings to other ethnicities, older populations, or those with complex comorbidities. Only two zoledronate infusions at a five-year interval were evaluated, leaving the optimal dosing frequency unresolved. Further, while adverse events appeared uncommon here, the sample size and population profile may not adequately capture rare or long-latency adverse outcomes.

Future Research: Larger trials in more diverse demographic and clinical settings are necessary to determine whether infrequent zoledronate can safely and effectively reduce fracture risk across broader patient groups. Studies comparing different dosing schedules, as well as investigations into cost-effectiveness and logistics of administration, would be highly valuable. Longer-term surveillance in real-world cohorts should help clarify the incidence of uncommon adverse events. Ultimately, such additional evidence will guide whether infrequent zoledronate infusions might be integrated into routine practice for fracture prevention in postmenopausal women without osteoporosis.

Reference:

Bolland MJ, Nisa Z, Mellar A, et al. Fracture Prevention with Infrequent Zoledronate in Women 50 to 60 Years of Age. New England Journal of Medicine. 2025;392:239-248. DOI: http://doi.org/10.1056/NEJMoa2407031
Chapurlat R. Infrequent Zoledronate — Small Individual Gain, Larger Population Gain. New England Journal of Medicine. 2025;392:281-283. DOI: http://doi.org/10.1056/NEJMe2415376

Screening for Osteoporosis to Prevent Fractures: Updated USPSTF Guidelines

18 Jan, 2025 | 15:19h | UTC

Introduction: This document summarizes the 2025 US Preventive Services Task Force (USPSTF) guideline on screening for osteoporosis to prevent fragility fractures. Osteoporosis, characterized by low bone mass and decreased bone quality, can lead to fractures that impair independence, increase morbidity, and raise mortality. The revised guidance builds on evidence that screening in select populations reduces fracture risk. Although the Task Force finds moderate net benefit for screening certain groups, it concludes that evidence remains insufficient to assess benefits and harms in other segments.

Key Recommendations:

Population and Rationale:
- Women 65 years or older: The USPSTF concludes with moderate certainty that screening for osteoporosis in this age group leads to moderate net benefit for preventing osteoporotic fractures.
- Postmenopausal women younger than 65 years at increased risk: Screening is recommended if a formal risk assessment or clinical risk factors indicate elevated risk, as moderate certainty suggests moderate benefit.
- Men: The current evidence is insufficient to establish the balance of benefits and harms of screening men without known osteoporosis or prior fragility fractures.
Screening Methods:
- The USPSTF identifies central dual-energy x-ray absorptiometry (DXA) of the hip or lumbar spine as the key screening test.
- In younger postmenopausal women, a two-step approach is suggested: (1) assess risk factors (e.g., low body weight, smoking, parental history of hip fracture); (2) apply a validated tool (e.g., Osteoporosis Risk Assessment Instrument [ORAI] or Osteoporosis Self-assessment Tool [OST]) to determine who should proceed to DXA.
- Tools such as FRAX may be used with or without BMD input to estimate 10-year fracture probability, but clinicians should be aware that tool accuracy and calibration vary by age, race/ethnicity, and underlying data sources.
Screening Intervals:
- Current data do not clearly define an optimal interval for repeated screening.
- Some evidence suggests little added value in repeating BMD tests within four to eight years if initial results are normal or only mildly low.
Management Following a Positive Screening Result:
- After osteoporosis is confirmed, patients should be counseled on modifiable risk factors (e.g., smoking cessation, fall prevention) and assessed for pharmacotherapy.
- Approved treatments (e.g., bisphosphonates, denosumab) have demonstrated benefit in reducing vertebral, hip, and other major fractures.
Harms of Screening and Treatment:
- Screening anxiety and overdiagnosis are minimal concerns, though data are limited.
- Bisphosphonate use has not been associated with significant excess serious adverse events in short- to medium-term trials, but rare events (e.g., atypical femur fractures, osteonecrosis of the jaw) remain possible with long-term use.
- Denosumab reduces multiple fracture outcomes, though discontinuation can lead to rebound bone loss and increased risk of vertebral fractures without follow-up management.
- The USPSTF underscores that treatment decisions should be individualized, especially in diverse populations and those with complex comorbidities.

Conclusion: These updated recommendations highlight the importance of osteoporosis screening in women 65 years or older and in younger postmenopausal women at higher fracture risk. Early detection with central DXA, informed by clinical risk tools, can reduce fracture incidence and related burdens. Further research is needed to clarify optimal screening intervals, the role of screening in men, and long-term treatment strategies. In the meantime, clinicians should collaborate with patients to personalize screening and treatment plans, considering both clinical risks and patient preferences.

Reference:

US Preventive Services Task Force. Screening for Osteoporosis to Prevent Fractures: US Preventive Services Task Force Recommendation Statement. JAMA. Published online January 14, 2025. DOI: http://doi.org/10.1001/jama.2024.27154
Editorials:
- Ensrud KE, Crandall CJ. Fracture Risk Assessment as a Component of Osteoporosis Screening—Easier Said Than Done. JAMA. Published online January 14, 2025. DOI: http://doi.org/10.1001/jama.2024.27416
- Ott SM. Research That Could Broaden the Scope of Bone Density Screening. JAMA Netw Open. 2025;8(1):e2460746. DOI: http://doi.org/10.1001/jamanetworkopen.2024.60746
Evidence Report:
- Kahwati LC, Kistler CE, Booth G, et al. Screening for Osteoporosis to Prevent Fractures: A Systematic Evidence Review for the US Preventive Services Task Force. JAMA. Published online January 14, 2025. DOI: http://doi.org/10.1001/jama.2024.21653

RCT: Empagliflozin Lowers Urinary Supersaturation in Nondiabetic Adults With Calcium and Uric Acid Kidney Stones

15 Jan, 2025 | 12:03h | UTC

Background: Kidney stones represent a major health challenge worldwide, with calcium-based (calcium oxalate or phosphate) and uric acid (UA) stones accounting for most cases. Despite multiple preventive measures—including hydration, dietary modification, and, in certain cases, pharmacotherapy—recurrence rates remain high. Recent retrospective analyses suggest sodium-glucose cotransporter 2 (SGLT2) inhibitors may reduce stone episodes in patients with type 2 diabetes. These agents could theoretically lower stone risk by promoting urinary citrate excretion, altering urine pH, and enhancing UA clearance. However, prospective data are lacking in nondiabetic individuals. This phase 2, single-center, double-blind, placebo-controlled, crossover study (SWEETSTONE) explored whether empagliflozin (25 mg daily) modifies urinary relative supersaturation ratios (RSRs)—a validated surrogate of stone risk—in adults without diabetes who have a history of either calcium or UA stones.

Objective: To determine if empagliflozin significantly reduces RSRs for calcium oxalate (CaOx), calcium phosphate (CaP), and UA in nondiabetic adults with recurrent kidney stones and to assess short-term safety.

Methods: A total of 53 participants (28 calcium stone formers, 25 UA stone formers) were randomized to empagliflozin 25 mg once daily or placebo for two weeks, followed by a 2–6-week washout, then crossed over to the alternative treatment. Primary outcomes were changes in RSR CaOx, RSR CaP, and RSR UA. Secondary measures included 24-hour urine pH, citrate, calcium, and UA, as well as key blood parameters. Analyses were performed separately for calcium and UA stone groups using a generalized linear mixed effects model. The per protocol set was used for the main analysis, with additional intention-to-treat assessments for confirmation.

Results: In calcium stone formers, empagliflozin lowered RSR CaP by 36% (95% CI −48% to −21%; p<0.001) compared with placebo but did not significantly change RSR CaOx. Uric acid supersaturation rose modestly, yet nonsignificantly. Among UA stone formers, empagliflozin reduced RSR UA by 30% (95% CI −44% to −12%; p=0.002), with no significant effect on RSR CaOx or RSR CaP. Both groups showed substantial increases in 24-hour urine citrate (60% for calcium stones, 40% for UA stones) and marked reductions in plasma UA levels. Urine calcium rose in some calcium stone formers, but no severe adverse events were reported during the study.

Conclusions: Short-term treatment with empagliflozin produced meaningful decreases in key urinary supersaturation indices among nondiabetic adults with calcium or UA stones, while exhibiting an acceptable safety profile. These favorable laboratory changes offer mechanistic promise but do not establish definitive evidence that long-term stone recurrence is reduced.

Implications for Practice: Although the pronounced improvement in urinary lithogenic profiles is encouraging, it remains unclear whether these shifts will translate into sustained reductions in actual stone formation. Consequently, clinicians should be cautious about recommending off-label SGLT2 inhibition for stone prevention solely on the basis of these short-term biochemical improvements. Larger, longer-duration trials with clinical endpoints (i.e., stone recurrence) are warranted before SGLT2 inhibitors can be broadly endorsed for this indication. In addition, practical considerations—such as cost, insurance coverage, and potential off-target effects—must be weighed in individualized clinical decisions.

Study Strengths and Limitations: Strengths include the randomized crossover design and distinct analyses for calcium and UA stone phenotypes. Nevertheless, the sample size was modest, and the treatment duration too brief to capture definitive impacts on stone recurrence. The predominance of white male participants also limits generalizability to more diverse populations.

Future Research: Extended follow-up is crucial to determine the long-term clinical effectiveness of empagliflozin in preventing stone events. Future work should also explore potential mechanisms in larger cohorts, assess cost-effectiveness in real-world settings, and evaluate whether other SGLT2 inhibitors elicit comparable effects.

Reference: Anderegg MA, Schietzel S, Bargagli M, et al. Empagliflozin in nondiabetic individuals with calcium and uric acid kidney stones: a randomized phase 2 trial. Nature Medicine (2025). DOI: https://doi.org/10.1038/s41591-024-03330-x

Observational Study Emulation: Denosumab vs. Oral Bisphosphonates in Dialysis-Dependent Patients Shows Reduced Fractures but Possible Elevated Cardiovascular Risk

8 Jan, 2025 | 11:55h | UTC

Background: Patients receiving dialysis have a markedly increased risk of osteoporotic fractures, yet management options in this population remain challenging. Although oral bisphosphonates are the usual first-line treatment for osteoporosis, safety concerns exist for those with severe chronic kidney disease (CKD). Denosumab, which is not cleared via the kidney, offers a potential alternative, but limited data compare its fracture-prevention benefit and cardiovascular (CV) safety against bisphosphonates in dialysis-dependent patients.

Objective: To estimate the risk for major adverse cardiac events (MACE) and the effectiveness in preventing fractures when using denosumab compared with oral bisphosphonates among patients undergoing dialysis.

Methods: This study emulated a target trial using an observational Japanese administrative claims database (April 2014 to October 2022). Adults aged 50 years or older, receiving dialysis and newly prescribed denosumab (60 mg subcutaneously) or oral bisphosphonates (alendronate, risedronate, ibandronate, or minodronate) were included. Exclusions involved recent acute myocardial infarction, stroke, or heart failure. Inverse probability of treatment weighting (IPTW) based on propensity scores was used to balance baseline characteristics. The primary safety outcome was MACE (acute myocardial infarction, stroke, hospitalization for heart failure, or CV death), and the primary effectiveness outcome was all fractures. Three-year risks, risk differences, and risk ratios were estimated.

Results: Among 658 denosumab users and 374 oral bisphosphonate users (mean age, 74.5 years; 62.9% women) followed for up to 3 years, denosumab was associated with a higher weighted risk of MACE (3-year risk ratio, 1.36 [95% CI, 0.99 to 1.87]; risk difference, 8.2% [–0.2% to 16.7%]) compared with oral bisphosphonates. Although the point estimate suggests a notable increase, the 95% CI includes 1.0, indicating that statistical significance was not definitively achieved. Denosumab showed a significantly lower composite fracture risk (3-year risk ratio, 0.55 [0.28 to 0.93]; risk difference, –5.3% [–11.3% to –0.6%]). Individual fracture sites (e.g., hip, vertebral) had imprecise estimates but trended toward fewer nonvertebral fractures with denosumab. Mortality rates did not differ substantially between the groups.

Conclusions: In dialysis-dependent patients with osteoporosis, denosumab may reduce fracture risk while potentially elevating the likelihood of MACE. However, the higher MACE estimate did not surpass the conventional threshold for statistical significance, warranting cautious interpretation. Although these data suggest a clinically meaningful reduction in fractures, the findings regarding cardiovascular outcomes remain imprecise and require further confirmation.

Implications for Practice: Clinicians treating dialysis-dependent patients should weigh denosumab’s fracture-prevention advantage against its possible heightened CV risk. Oral bisphosphonates, though sometimes restricted in severe CKD, may confer lower risk of MACE. Careful monitoring of electrolyte levels, especially calcium, and CV status is essential when administering denosumab in end-stage kidney disease.

Study Strengths and Limitations: Strengths include a large, real-world cohort and the use of target trial emulation with robust propensity score weighting. Limitations involve potential residual confounding, reliance on claims-based definitions of outcomes, and absent lab data (e.g., serum calcium, glomerular filtration rate). Consequently, causality and generalizability should be interpreted with caution, especially outside Japan.

Future Research:
Prospective trials and additional observational studies using detailed clinical data (including renal function parameters and bone mineral density) are needed to clarify the relative net benefits of denosumab versus bisphosphonates in advanced CKD. Investigations into other safety outcomes, such as long-term renal function and hypocalcemia-related complications, would further inform clinical decision-making.

Reference: Masuda S, Fukasawa T, Matsuda S, Kawakami K. “Cardiovascular Safety and Fracture Prevention Effectiveness of Denosumab Versus Oral Bisphosphonates in Patients Receiving Dialysis: A Target Trial Emulation.” Annals of Internal Medicine. DOI:
https://doi.org/10.7326/ANNALS-24-03237

Meta-analysis: Incidence Rate Difference of Adverse Events from Canabinoids in Middle-Aged and Older Adults

25 Dec, 2024 | 12:19h | UTC

Background: Growing evidence suggests that cannabinoid-based medicines (CBMs) are increasingly prescribed to individuals aged 50 years and above for various clinical conditions. While these agents may offer therapeutic benefits, questions remain about the incidence of adverse events (AEs), particularly in older adults with multiple comorbidities. This systematic review and meta-analysis aims to quantify the incidence rate difference (IRD) of AEs and determine whether weekly doses of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are associated with any dose-dependent increase in risk.

Objective: To evaluate whether adults aged ≥50 years exposed to CBMs, including THC-alone formulations and THC combined with CBD, experience a higher incidence of AEs than controls, and to assess how variations in weekly THC and CBD doses might affect AE rates.

Methods: Researchers searched MEDLINE, PubMed, EMBASE, CINAHL, PsychInfo, Cochrane Library, and ClinicalTrials.gov from January 1, 1990, to June 12, 2023. Randomized clinical trials involving middle-aged and older adults (mean age ≥50 years) using medicinal CBMs for all indications were included. Data on common and serious AEs, withdrawals, and deaths were extracted and pooled using a random-effects model. Further meta-regression analyses examined THC and CBD weekly doses as predictors of AEs in THC-only and THC:CBD trials.

Results: Fifty-eight randomized clinical trials (n=6611) met inclusion criteria, with 3450 participants receiving CBMs. Compared to controls, individuals on THC-alone experienced significantly higher incidence of dizziness, somnolence, impaired coordination, dissociative symptoms, and dry mouth, often in a dose-dependent manner. Similarly, THC:CBD combinations increased nausea, vomiting, fatigue, dizziness, and disorientation. The incidence of serious AEs, withdrawals, or mortality did not differ significantly between CBM and control groups, although neurological or psychiatric side effects were more pronounced with higher THC doses.

Conclusions: THC-containing CBMs can provoke dose-related gastrointestinal, neurological, and psychiatric adverse events, posing additional risks in older adults susceptible to falls and cognitive disturbances. However, the meta-analysis found no significant increases in serious AEs or deaths. Clinicians should weigh potential benefits against the likelihood of common side effects, especially when prescribing higher THC doses or combining cannabinoids with other medications frequently used by older patients.

Implications for Practice:

Physicians should exercise caution when initiating or escalating THC-based therapies in middle-aged and older adults, monitoring for neurological or psychiatric AEs.
Using lower THC doses, titrating gradually, and adding CBD may mitigate some side effects.
Though severe AEs are uncommon, vigilance is warranted in individuals with complex medication regimens.

Study Strengths and Limitations:

Strength: This review merges diverse clinical conditions and provides a comprehensive assessment of THC vs. THC:CBD. Its large pooled population allows for more precise IRD estimates.
Limitation: Short treatment durations in many trials limit understanding of long-term toxicity, and some studies lacked rigorous reporting of randomization and outcome measures, potentially introducing bias.

Future Research:

Longer-duration trials focused on older populations are needed to clarify chronic safety profiles.
Studies exploring drug-drug interactions between CBMs and medications commonly prescribed to older adults will further elucidate real-world tolerability.

Reference: Velayudhan L, Pisani S, Dugonjic M, McGoohan K, Bhattacharyya S. Adverse events caused by cannabinoids in middle aged and older adults for all indications: a meta-analysis of incidence rate difference. Age and Ageing. 2024;53(11):afae261. DOI: https://doi.org/10.1093/ageing/afae261

EULAR/PReS Guidelines for the Diagnosis and Management of Still’s Disease

20 Oct, 2024 | 17:41h | UTC

Introduction:

Still’s disease, encompassing systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still’s disease (AOSD), is a systemic inflammatory disorder characterized by spiking fevers, rash, arthralgia or arthritis, and elevated inflammatory markers. Historically treated as separate entities, sJIA and AOSD are now recognized as the same disease continuum. To unify and optimize diagnosis and management across all ages, the European Alliance of Associations for Rheumatology (EULAR) and the Paediatric Rheumatology European Society (PReS) have developed comprehensive, evidence-based recommendations.

Key Recommendations:

Unified Terminology: sJIA and AOSD are the same disease and should be collectively termed “Still’s disease” to standardize diagnosis and treatment. (Recommendation: strong)
Rapid Diagnosis Using Operational Definitions: Key clinical features include spiking fever ≥39°C lasting ≥7 days, transient rash coinciding with fever spikes, arthralgia or arthritis, and elevated inflammatory markers (CRP, ESR, neutrophils, ferritin). Arthritis is supportive but not essential for diagnosis. (Strong)
Diagnostic Biomarkers: Elevated serum interleukin-18 (IL-18) and S100 proteins strongly support the diagnosis and should be measured when available. (Moderate)
Exclude Alternative Diagnoses: Carefully consider infections, malignancies, other immune-mediated inflammatory diseases, and monogenic autoinflammatory disorders to avoid misdiagnosis. (Strong)
Treatment Goals: The ultimate goal is drug-free remission, defined as clinically inactive disease (CID) maintained for at least 6 months. CID entails absence of disease-related symptoms and normalization of ESR and CRP. Intermediate targets at specific time points guide treatment adjustments. (Strong)
Early Use of IL-1 and IL-6 Inhibitors: To avoid prolonged glucocorticoid use, prioritize early initiation of interleukin-1 (IL-1) or interleukin-6 (IL-6) inhibitors upon diagnosis. (Strong)
Glucocorticoid Tapering: Aim to achieve CID without glucocorticoids within 6 months. Maintain CID for 3–6 months before initiating tapering of biologic DMARDs. (Strong)
Monitor for Complications: Be vigilant for life-threatening complications, including macrophage activation syndrome (MAS) and lung disease (LD), which require prompt recognition and management. (Strong)
MAS Management: Consider MAS in patients with persistent fever, splenomegaly, elevated ferritin, cytopenias, abnormal liver function tests, coagulopathy, and hypertriglyceridemia. High-dose glucocorticoids are essential; anakinra, ciclosporin, and interferon-γ inhibitors may be added. (Strong)
LD Screening and Management: Screen patients for LD via clinical assessment and pulmonary function tests; high-resolution CT scans are indicated for symptomatic patients. The presence of LD is not a contraindication for IL-1 or IL-6 inhibitors. (Strong)

Conclusion: Implementing these unified, evidence-based recommendations is expected to improve the diagnosis and management of Still’s disease across all ages, leading to earlier intervention, optimized treatment strategies, reduced complications, and enhanced patient outcomes, including achieving drug-free remission.

Reference: Fautrel B, et al (2024). EULAR/PReS recommendations for the diagnosis and management of Still’s disease, comprising systemic juvenile idiopathic arthritis and adult-onset Still’s disease. Annals of Rheumatic Diseases. DOI: http://doi.org/10.1136/ard-2024-225851

Systematic Review: Anifrolumab and Belimumab Improve Disease Control in Systemic Lupus Erythematosus; Voclosporin and Belimumab Effective in Lupus Nephritis

20 Oct, 2024 | 14:26h | UTC

Background: Systemic lupus erythematosus (SLE) management remains challenging due to disease heterogeneity and varying severity. New studies since the 2019 EULAR recommendations necessitate an update to inform clinical practice.

Objective: To analyze new evidence (2018–2022) for SLE management to inform the 2023 update of the European League Against Rheumatism (EULAR) recommendations.

Methods: Systematic literature reviews (SLRs) were conducted in Medline and Cochrane Library databases, covering publications from January 2018 to December 2022. Research focused on five domains: (1) efficacy and safety of SLE treatments, (2) benefits of remission/low disease activity, (3) risks of treatment tapering/withdrawal, (4) management of SLE with antiphospholipid syndrome, and (5) safety of varicella zoster virus (VZV) and SARS-CoV2 immunizations.

Results: A total of 439 relevant articles were identified, predominantly observational studies of low or moderate quality. High-quality randomized controlled trials (RCTs) documented the efficacy of anifrolumab, a type 1 interferon receptor inhibitor, in non-renal SLE, and belimumab and voclosporin, a novel calcineurin inhibitor, in lupus nephritis (LN) when compared with standard care. For specific organ manifestations outside LN, high-quality data were lacking. Multiple observational studies confirmed the benefits of attaining clinical remission or low disease activity, reducing the risk of adverse outcomes. Two RCTs with some concerns found higher relapse rates in patients who discontinued glucocorticoids or immunosuppressants in SLE and LN, respectively; however, observational studies suggest that treatment withdrawal may be feasible in a subset of patients.

Conclusions: Anifrolumab and belimumab achieve better disease control than standard care in extrarenal SLE, while combination therapies with belimumab and voclosporin showed higher response rates in high-quality RCTs in LN. Remission and low disease activity are associated with favorable long-term outcomes. In patients achieving these targets, glucocorticoids and immunosuppressive therapy may be gradually tapered.

Implications for Practice: Clinicians should consider anifrolumab and belimumab for extrarenal SLE, and belimumab and voclosporin for LN. Monitoring and aiming for remission or low disease activity can reduce adverse outcomes. Gradual tapering of glucocorticoids and immunosuppressants may be considered in patients achieving these targets, with careful monitoring for relapse.

Study Strengths and Limitations: Strengths include comprehensive SLRs and inclusion of recent high-quality RCTs. Limitations involve the predominance of low-quality observational studies, lack of high-quality data for specific organ manifestations, and potential bias in treatment withdrawal studies.

Future Research: Further high-quality RCTs are needed to assess treatments for specific organ manifestations outside LN. Long-term studies on tapering and withdrawal strategies of immunosuppressive therapies are necessary to guide safe practice.

Reference: Kostopoulou M, Mukhtyar CB, Bertsias G, Boumpas DT, Fanouriakis A. Management of systemic lupus erythematosus: a systematic literature review informing the 2023 update of the EULAR recommendations. Annals of Rheumatic Diseases. 2023. DOI: https://doi.org/10.1136/ard-2023-225319

RCT: Zasocitinib Achieves Significant Psoriasis Improvement in Moderate to Severe Plaque Psoriasis

6 Sep, 2024 | 22:48h | UTC

Study Design and Population: This phase 2b, double-blind, placebo-controlled trial evaluated the efficacy, safety, and tolerability of zasocitinib, a selective tyrosine kinase 2 (TYK2) inhibitor, in patients with moderate to severe plaque psoriasis. Conducted across 55 centers in the US and Canada, the study enrolled 287 patients aged 18 to 70 years with a Psoriasis Area and Severity Index (PASI) score ≥12, and ≥10% of body surface area affected. Patients were randomized to receive zasocitinib at doses of 2 mg, 5 mg, 15 mg, or 30 mg, or a placebo, over 12 weeks.

Main Findings: At week 12, significant improvements in PASI were observed across all doses of zasocitinib. The primary endpoint of PASI 75 was achieved in 18%, 44%, 68%, and 67% of patients in the 2 mg, 5 mg, 15 mg, and 30 mg zasocitinib groups, respectively, compared to 6% in the placebo group. Higher PASI 90 and PASI 100 responses were also observed, particularly in the 15 mg and 30 mg groups. Adverse events were mild to moderate and occurred in 53% to 62% of patients receiving zasocitinib, compared to 44% for placebo.

Implications for Practice: Zasocitinib shows promise as an effective and well-tolerated oral treatment for moderate to severe plaque psoriasis. Its efficacy in achieving skin clearance (PASI 75 and above) at higher doses suggests potential for broader clinical use, with phase 3 trials warranted for further validation.

Reference: Armstrong, A.W. et al. (2024). Tyrosine Kinase 2 Inhibition with Zasocitinib in Psoriasis: A Randomized Clinical Trial. JAMA Dermatology. http://doi.org/10.1001/jamadermatol.2024.2701

Retrospective Cohort Study: Rheumatoid Arthritis Linked to Over 50% Increased Lung Cancer Risk, with a Three-Fold Risk in RA-Associated Interstitial Lung Disease – Arthritis Rheumatol

18 Aug, 2024 | 18:58h | UTC

Study Design and Population: This retrospective matched cohort study examined the risk of lung cancer in 72,795 patients with rheumatoid arthritis (RA) and 757 patients with RA-associated interstitial lung disease (RA-ILD) from the Veterans Health Administration database, compared with 633,937 non-RA controls. The study spanned from 2000 to 2019, with patients matched on age, gender, and enrollment year.

Main Findings: The study found that RA was associated with a 58% increase in lung cancer risk (adjusted hazard ratio [aHR] 1.58). The risk was significantly higher in RA-ILD patients, with a more than three-fold increase (aHR 3.25) compared to non-RA controls. Even among never smokers, RA patients showed a 65% increased lung cancer risk, indicating that factors beyond smoking contribute to the elevated risk.

Implications for Practice: The study underscores the significant increase in lung cancer risk among patients with RA, particularly those with RA-ILD. While this elevated risk is notable, further research is necessary to determine the most effective strategies for monitoring and managing this risk. Clinicians should be aware of these findings and consider them when evaluating the overall health and risk factors of patients with RA, especially those with additional pulmonary complications like ILD. Enhanced awareness and individualized risk assessments may help in early detection and management of lung cancer in this high-risk population.

Reference: Brooks RT, Luedders B, Wheeler A, et al. (2024). The Risk of Lung Cancer in Rheumatoid Arthritis and Rheumatoid Arthritis–Associated Interstitial Lung Disease. Arthritis & Rheumatology, 0(0), 1-9. DOI: 10.1002/art.42961.

Cohort Study: Efficacy of first-line color doppler ultrasound in diagnosing giant cell arteritis – Ann Intern Med

25 May, 2024 | 19:39h | UTC

This prospective multicenter study aimed to evaluate the efficacy of using color Doppler ultrasound of the temporal arteries as the first-line diagnostic tool for Giant Cell Arteritis (GCA) in 165 elderly patients with high clinical suspicion of the disease. The study followed participants over two years, comparing ultrasound results with temporal artery biopsy (TAB) and physician-based clinical diagnosis including other imaging tests. Key findings indicate that ultrasound confirmed GCA in 44% of cases, which was higher compared to TAB (17%) and clinical expertise (21%). The study showed that using ultrasound first can avoid the need for further invasive tests like TAB in patients with positive ultrasound results. The limitations of the study include its small sample size, unblinded test results, and the absence of a universally accepted objective diagnostic standard. However, it highlights the potential of ultrasound in the early and non-invasive diagnosis of GCA, potentially reducing the risk of severe complications by expediting treatment initiation.

Reference (link to abstract – $ for full-text):

Guillaume Denis et al. (2023). Diagnostic Strategy Using Color Doppler Ultrasound of Temporal Arteries in Patients With High Clinical Suspicion of Giant Cell Arteritis: A Prospective Cohort Study. Annals of Internal Medicine. DOI: 10.7326/M23-3417.

Cohort Study | Mortality risk in anti-MDA5 dermatomyositis linked to rapid ILD progression and anti-Ro52 antibody levels

11 Aug, 2023 | 15:21h | UTC

Mortality risk in patients with anti-MDA5 dermatomyositis is related to rapidly progressive interstitial lung disease and anti-Ro52 antibody – Arthritis Research & Therapy

Commentary on Twitter

High mortality risk predictors in patients with anti-MDA5 dermatomyositis include:
– rapidly progressive interstitial lung disease
– anti-Ro52 antibody
– age > 57 years
(based on study of 126 MDA-5+ DM pts)https://t.co/JLGIgALUip pic.twitter.com/boTTzrixk9

— Dr. John Cush (@RheumNow) August 5, 2023

Cohort Study | Vegetarian diet linked to elevated hip fracture risk; BMI plays a partial role

9 Aug, 2023 | 15:16h | UTC

Risk of hip fracture in meat-eaters, pescatarians, and vegetarians: a prospective cohort study of 413,914 UK Biobank participants – BMC Medicine

Systematic review informing the 2022 EULAR recommendations for the management of ANCA-associated vasculitis

7 Aug, 2023 | 14:47h | UTC

Systematic literature review informing the 2022 update of the EULAR recommendations for the management of ANCA-associated vasculitis (AAV): part 1—treatment of granulomatosis with polyangiitis and microscopic polyangiitis – RMD Open

Guideline: EULAR recommendations for the management of ANCA-associated vasculitis

Comparison of risankizumab and apremilast for the treatment of adult patients with moderate plaque psoriasis eligible for systemic therapy: results from a randomised, open-label, assessor-blinded phase IV (IMMpulse) study – British Journal of Dermatology

Commentary: Risankizumab Shown to be Superior to Apremilast in Treating Adults with Moderate Psoriasis – HCP Live

2023 ACR/EULAR classification criteria for calcium pyrophosphate deposition disease

2 Aug, 2023 | 14:02h | UTC

The 2023 ACR/EULAR Classification Criteria for Calcium Pyrophosphate Deposition Disease – Arthritis & Rheumatology

Commentary: 2023 ACR/EULAR Criteria for Calcium Pyrophosphate Deposition Disease – RheumNow

RCT | Baricitinib demonstrates efficacy in treatment-resistant juvenile idiopathic arthritis

2 Aug, 2023 | 13:45h | UTC

Baricitinib in juvenile idiopathic arthritis: an international, phase 3, randomised, double-blind, placebo-controlled, withdrawal, efficacy, and safety trial – The Lancet (link to abstract – $ for full-text)

Commentary on Twitter

NEW in @TheLancet—Baricitinib was efficacious with an acceptable safety profile in patients with #juvenile idiopathic #arthritis in a phase 3 withdrawal trialhttps://t.co/vZyXUwBiDZ #JIA

Plus linked Comment: https://t.co/VWofLvL427 pic.twitter.com/MGVoUz4xIv

— The Lancet Rheumatology (@TheLancetRheum) July 10, 2023

Novel therapeutics for management of lupus nephritis: what is next?

1 Aug, 2023 | 14:22h | UTC

Novel Therapeutics for Management of Lupus Nephritis: What Is Next? – Kidney Medicine

Review | First-line immunosuppression in neuromuscular diseases

1 Aug, 2023 | 14:09h | UTC

First-line immunosuppression in neuromuscular diseases – Practical Neurology

Cohort Study | More data suggests SGLT-2 inhibitors could reduce gout flares

26 Jul, 2023 | 13:24h | UTC

Comparative Effectiveness of Sodium–Glucose Cotransporter-2 Inhibitors for Recurrent Gout Flares and Gout-Primary Emergency Department Visits and Hospitalizations: A General Population Cohort Study – Annals of Internal Medicine (link to abstract – $ for full-text)

Commentaries:

SGLT-2 inhibitors reduced gout flares in patients with diabetes, gout – ACP Internist

SGLT2i Use Linked to Reduced Risk for Flare in Adults With Gout, T2D – HealthDay

SGLT2 inhibitors linked with fewer gout flares in diabetes – MDedge

Cohort Study | The role of antiphospholipid syndrome and specific antibodies in predicting SLE pregnancy complications

25 Jul, 2023 | 13:44h | UTC

Pregnancy outcomes in 1869 pregnancies in a large cohort from the Spanish Society of Rheumatology Lupus Register (RELESSER) – Seminars in Arthritis and Rheumatism (link to abstract – $ for full-text)

Commentary: SLE and Pregnancy Outcomes – RheumNow

M-A | Comparison of systemic treatments for chronic plaque psoriasis – Anti-IL17 stands out

25 Jul, 2023 | 13:27h | UTC

Systemic pharmacological treatments for chronic plaque psoriasis: a network meta‐analysis – Cochrane Library

Review | Hypereosinophilic syndrome (HES) and eosinophilic granulomatosis with polyangiitis (EGPA): two sides of the same coin

7 Jul, 2023 | 16:01h | UTC

HES and EGPA: Two Sides of the Same Coin – Mayo Clinic Proceedings