Can we predict if patients with SLE will require more than one cycle of rituximab?

OBJECTIVE: To identify clinical and serological features that distinguish patients with SLE who require single as opposed to repeated rituximab (RTX) cycles. METHODS: All 175 SLE patients followed up at University College Hospital from 2000 onwards were retrospectively reviewed. They were divided into a one-RTX-cycle group and a multiple-cycle group (2 or more cycles). Patients included had a follow-up of at least 3 years after their first RTX cycle, unless they needed a second infusion sooner. RESULTS: A total of 131 patients were included; 44 (33.6%) received one cycle of RTX and 87 (66.4%) received two or more. The former were older at diagnosis (31.4 vs 21 years, P < 0.001) and at first RTX infusion (39.9 vs 29 years, P < 0.001). This group of patients had more organs/systems involved (P = 0.044), more leukopenia, lymphopenia and thrombocytopenia (P = 0.001, P < 0.0001 and P = 0.003, respectively) and lower C3 levels (P = 0.035). They also had fewer immunosuppressive drugs before RTX therapy compared with those who required multiple RTX cycles (P = 0.003). There was no statistical difference in either the clinical or serological response after the first RTX cycle between both groups. Furthermore, patients who had received more immunosuppressive treatments were more likely to require more than one cycle of RTX infusions (P = 0.007). CONCLUSIONS: RTX is an effective option for SLE patients with severe flares. Patients who received more immunosuppressive drugs were more likely to receive more than one set of RTX infusions. This suggests that RTX is best used for SLE patients with no history of refractory disease.

Assessing outcomes in a lupus nephritis cohort over a 40-year period.

OBJECTIVES: To characterize a LN cohort over 40 years, assessing its evolution, analysing two major outcomes: the development of end-stage renal disease and mortality rates in the first 5 years after LN diagnosis. METHODS: An observational retrospective study of patients with LN, followed up from 1975 at University College Hospital. Patients were divided into four groups, depending on the decade of LN diagnosis: 1975-1985 (D1), 1986-1995 (D2), 1996-2005 (D3) and 2006-2015 (D4). Comparison between groups was performed with respect to demographic, clinical, serological and histological characteristics and outcome. RESULTS: Two hundred and nineteen patients with LN were studied. There was a change in ethnic distribution, with a decreasing proportion of Caucasians (58.6% in D1 to 31.3% in D4, P = 0.018) and increase in African-ancestry (17.2% in D1 to 39.6% in D4, P = 0.040). Serological and histological patterns changed throughout time, with a reduction in class IV nephritis (51.7% in D1 to 27.1% in D4, P = 0.035), and increase in class II nephritis (10% in D2 to 18.8% in D4, P = 0.01) and anti-extractable nuclear antigen antibody positivity (17.2% in D1 to 83.3% in D4, P = 0.0001). The 5-year mortality rates decreased from D1 (24.1%) to D2 (4%), stabilizing for the next 30 years. The 5-year progression to end-stage renal disease remained stable over the decades. CONCLUSION: Despite the changes in treatment of LN in the past 20 years, we have reached a plateau in 5-year mortality and progression to end-stage renal disease rates, suggesting that new therapeutic and management approaches, and strategies to enhance adherence, are needed to improve outcomes further in LN patients.

Frequency of C9orf72 hexanucleotide repeat expansion and SOD1 mutations in Portuguese patients with amyotrophic lateral sclerosis.

Mutation frequency of the 2 main amyotrophic lateral sclerosis (ALS)-related genes, C9orf72 and SOD1, varies considerably across the world. We analyzed those genes in a large population of Portuguese ALS patients (n = 371) and recorded demographic and clinical features. Familial ALS (FALS) was disclosed in 11.6% of patients. Mutations in either SOD1 or C9orf72 were found in 9.2% of patients and accounted for 40% of FALS and 5.2% of sporadic ALS. SOD1 mutations were rare (0.83%), but a novel and probably disease-causing mutation was identified: p.Ala152Pro (c.457G>C). The C9orf72 hexanucleotide repeat expansion was the commonest abnormality, accounting for 4.6% of sporadic ALS and 37.5% of FALS; in these patients, Frontotemporal Dementia was prevalent. This first report on the frequency of C9orf72 hexanucleotide repeat expansion and SOD1 mutations in Portuguese ALS patients reiterate that the genetic architecture of ALS varies among different geographic regions. The mutations incidence in ALS patients (∼10%) and associated phenotypes suggest that genetic tests should be offered to more patients, and other genes should be investigated in our population.