Tolerance and efficacy of targeted therapies prescribed for off-label indications in refractory systemic autoimmune diseases: data of the first 100 patients enrolled in the TATA registry (TArgeted Therapy in Autoimmune Diseases).

OBJECTIVES: To assess the tolerance and efficacy of targeted therapies prescribed off-label in refractory low-prevalence autoimmune and inflammatory systemic diseases. METHODS: The TATA registry (TArgeted Therapy in Autoimmune Diseases) is a prospective, observational, national and independent cohort follow-up. The inclusion criteria in the registry are as follows: age >18 years; low-prevalence autoimmune and inflammatory systemic disease treated with off-label drugs started after 1 January 2019. RESULTS: Hundred (100) patients (79 women) were enrolled. The median age was 52.5 years (95% CI 49 to 56) and the median disease duration before enrolment was 5 years (3 to 7). The targeted therapies at enrolment were as follows: Janus kinase/signal transducers and activators of transcription inhibitors (44%), anti-interleukin (IL)-6R (22%), anti-IL-12/23, anti-IL-23 and anti-IL-17 (9%), anti-B cell activating factor of the tumour necrosis factor family (5%), abatacept (5%), other targeted treatments (9%) and combination of targeted treatments (6%). 73% of patients were receiving corticosteroid therapy at enrolment (median dose 10 mg/day). The current median follow-up time is 9 months (8 to 10).Safety: 11 serious infections (incidence rate of 14.8/100 patient-years) and 1 cancer (1.3 cancers/100 patient-years) were observed. Two patients died from severe COVID-19 (2.7 deaths/100 patient-years).Efficacy: the targeted treatment was considered effective by the clinician in 56% of patients and allowed, in responders, a median reduction of oral corticosteroids of 15 (9 to 21) mg/day, below 7.5 mg/day in 76% of patients, while 28% discontinued. CONCLUSION: These initial results of the TATA registry confirm the diversity of targeted treatments prescribed off-label in refractory autoimmune diseases and their corticosteroid-sparing effect when effective. Tolerance was acceptable in these refractory patients with a long history of treatment with immunosuppressive drugs.

Tocilizumab versus Rituximab in Patients with Moderate to Severe Steroid-resistant Graves' Orbitopathy.

INTRODUCTION: To describe the efficacy of tocilizumab in patients with Graves' orbitopathy resistant or dependent to steroids and compare to rituximab treated patients. PATIENTS AND METHODS: Graves's orbitopathy response was considered as decrease of at least 2 points of the CAS. RESULTS: Twenty-one patients were included, 7 patients were treated with tocilizumab and 14 with rituximab. The primary was achieved in all 7 patients (100%) on tocilizumab and 9 out of 14 patients on (64%) rituximab (p = .17). Mean change in CAS was consistent with a decrease of 3.3 ± 0.5 points in patients on tocilizumab versus 2.5 ± 1.9 in patients on rituximab (p = .07). One patient on tocilizumab (14%) and 4 patients (29%) on rituximab experienced significant relapse during the follow-up. The difference in relapse-free survival was not significant in patients on tocilizumab (10.8 ± 4 months) compared with rituximab (17.88 ± 3.66). CONCLUSION: We showed a significant improvement in the CAS, visual acuity, diplopia, and proptosis with both tocilizumab and rituximab.

Overview of osteo-articular involvement in systemic sclerosis: Specific risk factors, clinico-sonographic evaluation, and comparison with healthy women from the French OFELY cohort.

Osteoarticular involvement in systemic sclerosis (SSc) is frequent and varied. Data are scarce on the prevalence and risk factors of osteoporosis (OP). We aimed to assess clinical parameters, radiological parameters, US articular involvements, and the frequency of OP and evaluate SSc-specific risk factors. In a prospective cohort of 54 patients with SSc, data of OP risk factors, SSc organ involvements, tender and swollen joint counts, DAS28-CRP, hand US sonographies, X-ray hand views, and bone mineral density (BMD) were assessed. BMD values were compared to those from a healthy female population (OFELY cohort). Nineteen patients (40%) had OP. SSc was a risk factor of lower BMD in the patient group than in the control group. OP was associated with SSc-related risk factors and not with conventional OP risk factors. Nine patients had clinical synovitis (16%), and 23 (68%) patients had at least one US synovitis. No correlation was found with articular destruction, disease severity, autoantibody profile, or other organ impairment.

Eosinophilic fasciitis (Shulman disease): new insights into the therapeutic management from a series of 34 patients.

OBJECTIVE: To analyse therapeutic management of eosinophilic fasciitis (EF). METHODS: We reviewed 34 adult patients with biopsy-proven EF. Analyses focused on the therapeutic management, including treatment modalities, responses and associated or predictive factors. RESULTS: Thirty-four patients were included with a diagnosis age of 53 (15) years. They were featured by cutaneous manifestations (88%) including morphoea (41%), myalgia (86%) and hypereosinophilia (85%). Thirty-two patients (94%) were eligible for treatment evaluation and all received CSs as a first-line therapy. Fifteen patients (47%) received methylprednisolone pulses (MPPs) at treatment initiation and 14 patients (44%) received an immunosuppressive drug (ISD), usually MTX (86%), as a second-line therapy. Complete remission was achieved for 69% of patients, remission with disability 19% and failure 12%. A poor outcome was associated with a diagnosis time delay of >6 months [odds ratio (OR) = 14.7] and the lack of MPPs (OR = 12.9). CONCLUSION: Our study reports new insights into the therapeutic management of EF: (i) CS treatment remains the standard therapy for EF, taken alone or in association with an ISD; (ii) MPPs at initiation of treatment are associated with a better outcome and a lower need of ISD use; (iii) an ISD, usually MTX, might be useful as a second-line therapy, mainly in patients with morphoea-like lesions. Naturally, these practical conclusions should be confirmed by a prospective and multicentre study.

Plasma homocysteine and the severity of heart failure in patients with previous myocardial infarction.

BACKGROUND: Homocysteine is considered to be a risk factor, or an indicator of risk, for the development of cardiovascular disease. Little data is available on its significance in patients with previous myocardial infarction. The aim of our study was to assess the plasma level of homocysteine and its relationship with the severity of heart failure in patients with chronic myocardial infarction. METHODS: We studied 144 patients with previous myocardial infarction. Patients were divided into two groups according to the presence or absence of heart failure, as certified by clinical evidence of heart failure and by echocardiographic criteria for left ventricular systolic dysfunction. RESULTS: Of the patients with prior myocardial infarction (144; 63.6 ± 9.6 years) included in the study, 65 had heart failure. The mean level of homocysteine was significantly higher in the heart failure group (18.9 mmol/L) than in the non-heart failure group (14.1 mmol/L; p ≤ 0.001). Our study demonstrated that there is a statistically significant correlation between homocysteine plasma levels and the severity of heart failure in patients with prior myocardial infarction. Homocysteine levels have proved to become higher with NYHA class progression. A significant cross-sectional correlation has been assessed between homocysteine and tissue Doppler echocardiography parameters. CONCLUSIONS: Increased plasma homocysteine levels independently correlate with the severity of heart failure in patients with chronic myocardial infarction. We suggest that homocysteine can be used in clinical practice as a valuable heart failure risk marker in patients with chronic myocardial infarction.

Vasculitides associated with malignancies: analysis of sixty patients.

OBJECTIVE: To describe characteristics and outcomes of vasculitides associated with malignancies. METHODS: The requirement for inclusion in this retrospective, 10-year study was development of vasculitis in patients with a progressing malignancy. Malignancies secondary to immunosuppressants used to treat vasculitis were excluded. The main characteristics of vasculitides were analyzed and compared according to the type of malignancy. RESULTS: Sixty patients were included (male/female sex ratio 2.53, mean age 62.4 years). Mean followup duration was 45.2 months. Vasculitides were cutaneous leukocytoclastic (45%), polyarteritis nodosa (36.7%), Wegener's granulomatosis (6.7%), microscopic polyangiitis (5%), and Henoch-Schönlein purpura (5%). Malignancies were distributed as follows: hematologic in 63.1%, myelodysplastic syndrome (MDS) in 32.3%, lymphoid in 29.2%, and solid tumor in 36.9%. Vasculitides were diagnosed concurrently with malignancy in 38% of the cases. Manifestations of vasculitides were fever (41.7%), cutaneous involvement (78.3%), arthralgias (46.7%), peripheral neuropathy (31.7%), renal involvement (23.3%; 11.7% glomerulonephritis, 11.7% microaneurysms, 6.7% renal insufficiency), and antineutrophil cytoplasmic antibody (20.4%). Vasculitis treatments were corticosteroids (78.3%) and immunosuppressant(s) (41.7%). Vasculitis was cured in 65% of patients, but 58.3% died, with 1 death secondary to vasculitis. Independent of subtype, patients with vasculitides associated with MDS more frequently had renal manifestations (P = 0.02) and steroid dependence (P = 0.04) and achieved complete remission less often (P = 0.04) than patients with vasculitides associated with other malignancies. Patients with vasculitides associated with a solid tumor more frequently had peripheral neurologic involvement (P = 0.05). Patients with vasculitides associated with lymphoid malignancy had less frequent arthralgias (P = 0.01) and renal involvement (P = 0.02). CONCLUSION: Vasculitides occurring during malignancies present distinctive features according to the vasculitis subtype and nature of the malignancy.