Demographic, clinical and antibody characteristics of patients with digital ulcers in systemic sclerosis: data from the DUO Registry

OBJECTIVES: The Digital Ulcers Outcome (DUO) Registry was designed to describe the clinical and antibody characteristics, disease course and outcomes of patients with digital ulcers associated with systemic sclerosis (SSc). METHODS: The DUO Registry is a European, prospective, multicentre, observational, registry of SSc patients with ongoing digital ulcer disease, irrespective of treatment regimen. Data collected included demographics, SSc duration, SSc subset, internal organ manifestations, autoantibodies, previous and ongoing interventions and complications related to digital ulcers. RESULTS: Up to 19 November 2010 a total of 2439 patients had enrolled into the registry. Most were classified as either limited cutaneous SSc (lcSSc; 52.2%) or diffuse cutaneous SSc (dcSSc; 36.9%). Digital ulcers developed earlier in patients with dcSSc compared with lcSSc. Almost all patients (95.7%) tested positive for antinuclear antibodies, 45.2% for anti-scleroderma-70 and 43.6% for anticentromere antibodies (ACA). The first digital ulcer in the anti-scleroderma-70-positive patient cohort occurred approximately 5 years earlier than the ACA-positive patient group. CONCLUSIONS: This study provides data from a large cohort of SSc patients with a history of digital ulcers. The early occurrence and high frequency of digital ulcer complications are especially seen in patients with dcSSc and/or anti-scleroderma-70 antibodies

Efficacy and safety of FOLFIRI/Aflibercept (FA) in an elderly population with metastatic colorectal cancer (mCRC) after the failure of an oxaliplatin-based regimen

Introduction: Aflibercept (ziv-aflibercept) significantly improves progression-free (PFS) and overall survival (OS) when added to FOLFIRI, compared with FOLFIRI alone, in the overall population of patients pretreated with oxaliplatin-based therapy. A subset analysis of elderly patients included in the registration VELOUR trial suggested that elderly (> 65 years) patients have a consistent, albeit small benefit in OS in PFS and a higher percentage of grade 3-4 toxicity. Our hypothesis was that selected patients with good PS could benefit from FOLFIRI-aflibercept (FA), provided they underwent careful monitoring of toxicity, and rapid intervention. Methods: We conducted a retrospective, multicentre, observational study of elderly patients (> 70 years) with mCRC treated with FOLFIRI-aflibercept after progression on an oxaliplatin-based regimen as part of routine clinical practice at seven hospitals from the Galician Research Group on Digestive Tumours (GITuD). Results: Of 315 patients treated with FA between June 2013 to November 2018, 71 elderly patients were recorded in this study. Median age was 72.7 years (range 70-84 years) and 33.4% were over 75 years (compared with only 14% in the VELOUR study subanalysis), 66.2 % were male, 83.1 % ECOG PS0-1, 43.7 % left-sided location, 76.1 % low grade, 63.4% RASmt and 2.8% BRAFmt, 66.2 % synchronous presentation and 77.5 % primary tumor resection. Prior therapy included bevacizumab (57.7%) and anti-EGFR agents (22.5%). Median of FA cycles was 9 (range 1-35 cycles). Overall Response Rate (ORR) and disease control rate (DCR) were 31.0 % and 63.4 %, respectively. With a median follow up of 27.1 months, median PFS was 6.6 months (95% CI, 5.0-8.3 months) and median OS was 15.1 months (95% CI, 12.1-18.1 months). The most common grade 3-4 toxicities were asthenia (18.3%), neutropenia (15.5%), diarrhoea (11.3%) and mucositis (9.9%). Aflibercept most common grade 3-4 related toxicities were hypertension (5.6%), dysphonia (5.6%), proteinuria (2.8%). Two patients experienced grade 5 toxicity (1 cerebrovascular event and 1 bowel perforation). This toxicity was managed with dose reduction of aflibercept in 39.4 % of cases, dose reduction of FOLFIRI on 57.7% and led to the discontinuation of aflibercept in 39.4%. Conclusion: Older patients with mCRC are underrepresented in clinical trials. The VELOUR study included only 6.4% patients over 65 years of age and only 14% of those over 65 were 75 years or older. Elderly patients treated with FA in the VELOUR trial experienced a higher rate of G3-4 adverse events (89.3% versus 80.5%) but this increase in toxicity was even more evident in the control arm (67.4% versus 59.4%). Our series confirms that with careful dose adjustment based on toxicity, including dose interruption if necessary elderly patients can be treated with FA with a 49.3% of grade 3-4 toxicity a PFS of 6.6 months and OS of 15.1 months, results that are comparable to those of younger patients

Elucidating the burden of recurrent and chronic digital ulcers in systemic sclerosis: long-term results from the DUO Registry

Objectives Digital ulcers (DUs) occur in up to half of patients with systemic sclerosis (SSc) and may lead to infection, gangrene and amputation with functional disability and reduced quality of life. This study has elucidated the burden of SSc-associated DUs through identification of four patient categories based on the pattern of DU recurrence over a 2-year observation period.Methods Patients with SSc-associated DUs enrolled in the Digital Ulcers Outcome Registry between 1 April 2008 and 19 November 2013, and with 2years of observation and 3 follow-up visits during the observation period were analysed. Incident DU-associated complications were recorded during follow-up. Work and daily activity impairment were measured using a functional assessment questionnaire completed by patients after the observation period. Potential factors that could predict incident complications were identified in patients with chronic DUs.Results From 1459 patients, four DU occurrence categories were identified: 33.2% no-DU; 9.4% episodic; 46.2% recurrent; 11.2% chronic. During the observation period, patients from the chronic category had the highest rate of incident complications, highest work impairment and greatest need for help compared with the other categories. Independent factors associated with incident complications included gastrointestinal manifestations (OR 3.73, p=0.03) and previous soft tissue infection (OR 5.86, p=0.01).Conclusions This proposed novel categorisation of patients with SSc-associated DUs based on the occurrence of DUs over time may help to identify patients in the clinic with a heavier DU burden who could benefit from more complex management to improve their functioning and quality of life

Functional impairment of systemic scleroderma patients with digital ulcerations: results from the DUO Registry

Objective. Digital ulcers (DUs) are frequent manifestations of systemic scleroderma (SSc). This study assessed functional limitations due to DUs among patients enrolled in the Digital Ulcer Outcome (DUO) Registry, an international, multicentre, observational registry of SSc patients with DU disease. Methods. Patients completed at enrolment a DU-specific functional assessment questionnaire with a 1-month recall period, measuring impairment in work and daily activities, and hours of help needed from others. Physician-reported clinical parameters were used to describe the population. For patients who completed at least part of the questionnaire, descriptive analyses were performed for overall results, and stratified by number of DUs at enrolment. Results. This study included 2327 patients who completed at least part of the questionnaire. For patients with 0, 1-2, and DUs at enrolment, mean overall work impairment during the prior month among employed/self-employed patients was 28\%, 42\%, and 48\%, respectively. Across all included patients, ability to perform daily activities was impaired on average by 35\%, 54\%, and 63\%, respectively. Patients required a mean of 2.0, 8.7, and 8.8 hours of paid help and 17.0, 35.9, and 63.7 hours of unpaid help, respectively, due to DUs in the prior month. Patients with DUs had more complications and medication use than patients with no DUs. Conclusion. With increasing number of DUs, SSc patients reported more impairment in work and daily activities and required more support from others