Clinical and experimental rheumatology最新文献

Objectives: This paper aims to provide insight into the challenges and opportunities of conducting an investigator-led, international, multicentre clinical trial for Inclusion Body Myositis (IBM), a rare inflammatory myopathy.

Methods: An international, multicentre, randomised, controlled trial of a repurposed drug (sirolimus) was initiated based on promising results from a mono-centric pilot study. The progress of the trial was analysed to identify key challenges encountered and solutions developed.

Results: This large, collaborative study has presented a mosaic of challenges and opportunities, many ubiquitous with investigator-led trials. Key challenges have included securing adequate funding, coordinating manufacture of placebo, negotiating international contracts, managing limited study budgets and delays linked to the COVID-19 pandemic. Alongside these challenges, the study team have found opportunities for creative and effective solutions, including the flexibility of building study databases, optimising digital data capture and harnessing patient involvement.

Conclusions: Instrumental to the progress of the trial has been the collaboration between site teams, patient partnership and adaptability.

Objectives: We aimed to examine the diagnostic utility of temporal artery ultrasonography (TAUS) based on measurement of intima-media thickness (IMT) compared with the halo sign in diagnosing cranial giant cell arteritis (GCA).

Methods: We retrospectively analysed consecutive patients with clinically suspected GCA who had undergone TAUS between January 2011 and December 2021 in Tenri hospital, Japan. A cut-off value of 0.5 mm was used for the IMT of the temporal arteries. We examined the diagnostic value of TAUS based on each of the halo sign and increased IMT in diagnosing cranial GCA.

Results: In total, 203 patients were included. Temporal artery biopsy (TAB) was performed in 59 patients, with 32 being biopsy-positive. Fifty-three patients were diagnosed with cranial GCA. The sensitivity and specificity of TAUS based on the increased IMT and halo sign were as follows: sensitivity, 62.3% and 32.1%; specificity, 90.0% and 100% compared with the clinical diagnosis; and sensitivity, 81.2% and 46.9%; specificity, 76.9% and 96.2% compared with the TAB. When the relationship between the IMT and halo sign was evaluated, patients with cranial GCA who presented with the halo sign had the highest IMT compared with those without the halo sign or those without cranial GCA.

Conclusions: A TAUS diagnosis relying only on the halo sign is specific but can underestimate cranial GCA. Therefore, evaluation of the IMT in addition to the halo sign can improve the diagnostic accuracy of TAUS when diagnosing cranial GCA.

Objectives: The incidence of cytomegalovirus (CMV) infection or disease in patients with rheumatic musculoskeletal diseases is reported to be 2%. Over half received pulsed methylprednisolone, and some experienced a fatal outcome. In this study, we aimed to explore predictive and diagnostic biomarkers for CMV infection or disease in such patients and compare them with biomarkers reported for immune reconstitution inflammatory syndrome (IRIS) in people with HIV.

Methods: In this multicentre prospective cohort study, we collected blood and saliva samples from 38 patients with rheumatic musculoskeletal disease before initiating high-dose glucocorticoid therapy, at the start of glucocorticoid tapering, at the onset of CMV infection, and 4 weeks later. Peripheral blood cell counts, flow cytometry for CD4, CD8, and Tregs, ELISA for cytokine/chemokine panels, and measurements of herpesvirus-derived DNA in saliva were performed.

Results: Lower white blood cells, CD4+ cells, IL-6, and interferon-γ levels and higher interferon-inducible protein (IP)-10 and granulysin levels at baseline could be predictive biomarkers for CMV infection. Furthermore, lower platelet counts and higher IL-10, IP-10, granulysin, TNF-a, IL-1ra, and IL-15 levels at the onset of CMV infection were found as diagnostic biomarkers for CMV infection. EBV, human herpes virus (HHV)-6, and HHV-7 DNA levels in the saliva were significantly increased after high-dose glucocorticoids, regardless of CMV infection.

Conclusions: We identified predictive and diagnostic biomarkers for CMV infection after high-dose glucocorticoid therapy for rheumatic musculoskeletal diseases. While similarities with IRIS biomarkers in patients living with HIV were observed, complete agreement could not be confirmed.

Objectives: Immune-mediated adverse events (irAEs) from immune checkpoint inhibitors (ICIs) often require high-dose glucocorticoids (GCs), which can promote cancer progression and counteract ICI benefits. This study evaluated the articular and oncologic clinical outcomes of ICI-induced arthritis treated with methotrexate (MTX) as a GC-sparing agent.

Methods: Adult patients with ICI-induced arthritis in 2023 were included. Arthritis was assessed using the disease activity score on 28 joints by C-reactive protein (DAS28-CRP), with follow-ups every 3 months. All patients received subcutaneous MTX, and oncologic outcomes were evaluated using RECIST 1.1 criteria after one year.

Results: Fourteen patients (median age 74.5 years) with melanoma (64.3%), colorectal cancer (14.3%), lung cancer (14.3%), or Hodgkin's lymphoma (7.1%) were treated with PD1 antagonists (92.9%) or combined with CTLA4 blockers (7.1%). Arthritis presentations included oligo-arthritis (36%), mono-arthritis (29%), polyarthritis (21%), and polymyalgia rheumatica-like syndrome (14.3%), with a mean onset of 4.7±3.7 months post-ICI. MTX was started for all at a mean dose of 9.5±1.5 mg weekly, beginning at the first rheumatology visit in 78.5% of patients. Over a mean follow-up of 12.8±4.6 months, DAS28-CRP scores improved significantly, and prednisone dosage was in all reduced (3.6 mg at V4 vs. 8.4 mg at V0, p=0.003). No major MTX-related toxicities were noted. Cancer responses at follow-up were complete (50%), partial (21.4%), stable disease (7.1%), and progression (21.5%).

Conclusions: The use of MTX in ICI-induced arthritis showed promising results in reducing GC dosages and managing the inflammatory articular activity, with no major toxicities observed over one year. These findings suggest that MTX may be a viable GC-sparing option in this context, but larger, controlled studies are needed to confirm these observations and better understand the impact on both articular and oncologic outcomes.