ciclosporin (Gengraf / ciclosporin, AbbVie)

Determining value and the contribution of ciclosporin-based therapies in dry eye disease: a European expert MCDA pilot study.

Ahmad Sajjad S, Figueiredo Francisco F, Labetoulle Marc M, Messmer Elisabeth M EM et al.

Dry eye disease (DED) is a multifactorial, immune-mediated inflammatory condition affecting the ocular surface and lacrimal glands. Multiple ciclosporin-based therapies with different formulations are currently available in Europe, although clear guidance on their optimal use remains limited. The aim of this study was to determine the main unmet needs and the current management landscape of ciclosporin-based therapies, from the perspective of clinical experts using multi-criteria decision analysis (MCDA). A systematic literature review was conducted to gather evidence for each of the MCDA framework criteria. An international expert panel of seven clinical specialists in DED from four European countries independently weighted the criteria and scored the non-comparative criteria in the evidence matrix. Results were presented and discussed in a group online session. DED is a highly prevalent, chronic inflammatory disease associated with significant visual and functional burden. Its management is not uniform and often involves a stepwise approach. Recent ciclosporin-based treatment alternatives address some unmet needs; however, others-such as the need for greater standardization of diagnostic tools and improved objective markers of inflammation-remain to be addressed. Highest importance was assigned to Efficacy/effectiveness (4.7 ± 0.5), Quality of evidence (4.7 ± 0.5), and Safety/tolerability (4.6 ± 0.5) criteria, highlighting the relevance of treatment-related outcomes in clinical decision-making. The expert opinion, based on MCDA, enabled the identification of key value drivers and unmet needs in the current management of DED based on ciclosporin-based therapies. These early insights may contribute to promoting future work to support informed, evidence-based decision-making.

Postpartum macrophage activation syndrome with temporal dissociation of cytopenias in a patient with Kikuchi-Fujimoto disease and undifferentiated connective tissue disease: a case report.

Zhou Xiying X, Li Jing J, Ma Yanhua Y, Liang Xuxia X

Macrophage activation syndrome (MAS) is a life-threatening hyperinflammatory disorder; postpartum MAS is extremely rare and often misdiagnosed due to overlap with sepsis and HELLP syndrome. Kikuchi-Fujimoto disease (KFD) and undifferentiated connective tissue disease (UCTD) may increase susceptibility, but reports are scarce. This case highlights the diagnostic challenges of postpartum MAS in the setting of overlapping inflammatory conditions. The patient was a 35-year-old primiparous woman with KFD and UCTD who underwent cesarean section for preeclampsia and cervical insufficiency. She developed septic shock postoperatively. Despite infection control, persistent fever and a distinct temporal dissociation emerged: platelets recovered from 12 to 198 ×109/L while neutrophils initially remained normal but subsequently declined to 0.04×109/L. Hyperferritinemia (>1,500 μg/L), hypertriglyceridemia (3.88 mmol/L), and hypofibrinogenemia (1.78 g/L) developed. The HScore was 176, exceeding the established cutoff of 169 associated with a high probability of reactive hemophagocytic syndrome. Natural killer (NK) cell activity was 2.76% (normal >15%), whereas serum sCD25 was unexpectedly low (<1.2 U/mL; reference range, 17.1-56.6 U/mL). Dexamethasone monotherapy failed, but adding ciclosporin led to rapid recovery. To our knowledge, postpartum MAS associated with KFD and UCTD has rarely been reported. This case demonstrates that a low or normal sCD25 level does not necessarily exclude the diagnosis of MAS. The temporal dissociation of platelet recovery preceding neutrophil decline may provide an early clue to distinguish evolving MAS from controlled infection. Prompt combination immunosuppressive therapy can be life-saving.

The FAST Study: Examining Quality of Vision Outcomes in Dry Eye Disease Patients with Severe Keratitis Treated with the Ciclosporin A Cationic Emulsion.

Pisella Pierre-Jean PJ, Mourad Amrane A, Ismail Dahlia D, Garrigue Jean-Sebastien JS et al.

Examination of the relationship between improvements in dry eye disease (DED) signs and changes in functional visual acuity (FVA) parameters with ciclosporin A 0.1% cationic emulsion (CsA 0.1% CE) treatment. Adults with DED and severe keratitis were included in a Phase IV, prospective, open-label, multicenter, single-arm, proof-of-concept study. Patients instilled CsA 0.1% CE (one drop daily) and unpreserved artificial tears from baseline through month 3. Primary endpoints examined the change from baseline in corneal fluorescein staining (CFS) score (modified Oxford scale) and any correlation with changes in visual maintenance ratio (VMR) or objective scatter index (OSI) variance. Other endpoints included the change from baseline in CFS score, LogMAR FVA and reporting of adverse events (AEs). Seventeen DED patients were included. Spearman's correlation analyses showed CFS reductions from baseline were significantly correlated with VMR increases (ρ = -0.70; P = 0.0017) at month 3 but not with OSI variance changes (ρ = -0.04; P = 0.8837). Mean CFS score was reduced from 3.8 (baseline) to 1.8 (month 3). CFS reduction significantly correlated with LogMAR FVA changes at month 3 (ρ = 0.6005; P = 0.0139). Seven patients experienced mild/moderate ocular treatment-related AEs and one had severe eye burn. No discontinuations occurred due to treatment-related AEs and there were no serious or sight-threatening events. DED patients with severe keratitis treated with CsA 0.1% CE demonstrated reductions in CFS score that were strongly and significantly correlated with improvements in quality of vision indicators, including VMR and LogMAR FVA. CsA 0.1% CE was well tolerated throughout the study period.

Correction: Long-Term Evolution of Treatment Outcomes with Once-Daily Ciclosporin A 0.1% Cationic Emulsion in Patients with Dry Eye Disease and Severe Keratitis.

Leonardi Andrea A, Aragona Pasquale P, Sainz de la Maza Maite M, Seleznev Aleksei A et al.