Dexamethasone prodrug nanomedicine (ZSJ-0228) treatment significantly reduces lupus nephritis in mice without measurable side effects - A 5-month study.

Lupus nephritis (LN) is a major cause of morbidity and mortality among systemic lupus erythematosus patients. Glucocorticoids (GCs) are uniformly used in clinical LN management. Their notorious toxicities, however, have hampered the long-term clinical application. To circumvent GC side effects while maintaining their potent therapeutic efficacy, we have developed a macromolecular prodrug nanomedicine based on dexamethasone (ZSJ-0228). The focus of this study was to investigate its long-term efficacy and, most importantly, safety in the lupus-prone NZB/W F1 mouse. Monthly ZSJ-0228 treatment for five months significantly reduced the incidence of nephritis in NZB/W F1 mice with an improved survival rate. In contrast to treatment with dose equivalent daily free dexamethasone, long-term monthly ZSJ-0228 did not result in any measurable GC-associated side effects. With its outstanding efficacy and exceptional safety, it is anticipated that ZSJ-0228 may be a novel therapy for long-term clinical management of LN.

Pulmonary manifestations in late versus early systemic lupus erythematosus: A systematic review and meta-analysis.

OBJECTIVES: Phenotypes differ between late- and early-onset systemic lupus erythematosus (SLE). Prior studies suggested that there may be more pulmonary disease among late-onset patients. Our objective was to perform a systematic review and meta-analysis to evaluate the differences in pulmonary manifestations in late- versus early-onset SLE. METHODS: We searched the literature using PubMed, CINAHL, Web of Science, Cochrane Library, and EMBASE. We excluded studies that did not include American College of Rheumatology SLE classification criteria, an early-onset SLE comparison group, or those that defined late-onset SLE as <50 years of age. We rated study quality using the Newcastle-Ottawa Quality Scale. We used Forest plots to compare odds ratios (95% confidence intervals) of pulmonary manifestations by age. Study heterogeneity was assessed using I2. RESULTS: Thirty-nine studies, representing 10,963 early-onset and 1656 late-onset patients with SLE, met eligibility criteria. The odds of developing several pulmonary manifestations were higher in the late-onset group. Interstitial lung disease (ILD) was nearly three times more common (OR = 2.56 (1.27, 5.16)). Pleuritis (OR = 1.53 (1.19, 1.96)) and serositis (OR = 1.31 (1.05, 1.65)) were also more common in the late-onset group. The mean Newcastle-Ottawa Quality Scale score for study quality was moderate (6.3 ± 0.7, scale 0-9). CONCLUSIONS: Pulmonary manifestations of SLE were more common in late-onset SLE patients compared to their younger peers, in particular ILD and serositis. Age-related changes of the immune system, tobacco exposure, race, and possible overlap with Sjögren's syndrome should be examined in future studies.

A systematic review and meta-analysis of cutaneous manifestations in late- versus early-onset systemic lupus erythematosus.

OBJECTIVES: Although systemic lupus erythematosus (SLE) most commonly occurs in reproductive-age women, some are diagnosed after the age of 50. Recognizing that greater than one-third of SLE criteria are cutaneous, we undertook a systematic review and meta-analysis to evaluate differences in cutaneous manifestations in early- and late-onset SLE patients. METHODS: We searched the literature using PubMed, CINAHL, Web of Science, and Cochrane Library. We excluded studies that did not include ACR SLE classification criteria, early-onset controls, that defined late-onset SLE as <50 years of age, or were not written in English. Two authors rated study quality using the Newcastle Ottawa Quality Scale. We used Forest plots to compare odds ratios (95% CI) of cutaneous manifestations by age. Study heterogeneity was assessed using I(2). RESULTS: Overall, 35 studies, representing 11,189 early-onset and 1727 late-onset patients with SLE, met eligibility criteria. The female:male ratio was lower in the late-onset group (5:1 versus 8:1). Most cutaneous manifestations were less prevalent in the late-onset group. In particular, malar rash [OR = 0.43 (0.35, 0.52)], photosensitivity [OR = 0.72 (0.59, 0.88)], and livedo reticularis [OR = 0.33 (0.17, 0.64)] were less common in late-onset patients. In contrast, sicca symptoms were more common [OR = 2.45 (1.91, 3.14)]. The mean Newcastle Ottawa Quality Scale score was 6.3 ± 0.5 (scale: 0-9) with high inter-rater reliability for the score (0.96). CONCLUSIONS: Overall, cutaneous manifestations are less common in late-onset SLE patients, except sicca symptoms. Future studies should investigate etiologies for this phenomenon including roles of immune senescence, environment, gender, and immunogenetics.