A randomized clinical trial of bermekimab treatment for clinical improvement of systemic sclerosis.

Increased concentrations of interleukin (IL)-1α have been recently described in tissues of patients with systemic sclerosis (SSc) suggesting that IL-1α inhibition may be a target for treatment. We conducted a double-blind, placebo-controlled study to assess the safety and efficacy of the fully humanized IL-1α blocking monoclonal antibody bermekimab in SSc. To evaluate response to treatment, we developed the score of inhibition of progression of SSc which was validated using the CRISS index and the modified CRISS index. The primary endpoint was met in 80% of bermekimab-treated patients vs. 20% of placebo-treated patients (p: 0.023). Most of efficacy was found for increase of carbon monoxide lung diffusion capacity. Production of IL-1α and TNF by circulating mononuclear cells was decreased and the absolute count of CD42/Cd62-platelets was decreased. Results suggest that bermekimab is a promising treatment for SSc.

Apremilast for biologic-naïve, peripheral psoriatic arthritis, including patients with early disease: results from the APROACH observational prospective study.

To evaluate the effect of the phosphodiesterase 4 inhibitor apremilast in biologic-naïve patients with early peripheral PsA in terms of disease activity, clinical manifestations, patient-perceived outcomes, as well as apremilast's safety profile in routine care settings of Greece. Non-interventional, multicenter, 52-week prospective cohort study, enrolling biologic-naïve patients with early active peripheral PsA who started apremilast after intolerance or inadequate response (within the first 12 months of treatment) to an initial conventional synthetic (cs)DMARD treatment. Non-responder imputation was applied for missing data.In total, 167 consecutive patients (mean age: 52.5 years; median PsA duration: 0.9 years) were analyzed. At baseline, the median (interquartile range) clinical Disease Activity in Psoriatic Arthritis (cDAPSA) score was 22.0 (16.0-29.0), with 86.8% of patients having at least moderate (29.3% high) disease activity; 87.4% had skin psoriasis, 37.7% nail psoriasis, 30.7% enthesitis, and 12.4% dactylitis. At 16, 24, and 52 weeks, 28.7, 42.5, and 48.5% of patients, achieved ≥ 50% improvement in their baseline cDAPSA score, respectively. At week 52, 55.6, 50, and 26.8% of evaluable patients achieved complete resolution of enthesitis, dactylitis and nail psoriasis, respectively. Improvements were also observed in patient's health state assessed by the Psoriatic Arthritis Impact of Disease 12-item questionnaire, and health-related quality of life. The 52-week drug survival rate was 75%, while 13.8% of patients experienced at least one adverse drug reaction.Biologic-naïve patients with early PsA, treated with apremilast experienced significant improvements in disease activity, extra-articular manifestations and patient-centered outcomes, accompanied by a favorable tolerability profile.

Spontaneous Chalk-Stick Fracture in Ankylosing Spondylitis: A Case Report.

Ankylosing spondylitis (AS) is an inflammatory disease affecting mainly the sacroiliac joints and the spine. In long-standing disease, the fused spine of AS patients is susceptible to spinal fractures, even after low impact trauma. We present a 61-year-old man with long-standing AS who presented with anterior and posterior longitudinal ligament rupture and T12 and L1 vertebral endplates fractures (a so called "chalk-stick fracture") without reporting any prior trauma and discuss relevant issues.

Septic Arthritis Complicating a Gout Flare: Report of Two Cases and Review of the Literature.

Objective: To highlight potential pitfalls in diagnosis and management of patients with concomitant gout and septic arthritis. Methods: Presentation of two patients with concomitant gout and septic arthritis, the latter caused by Streptococcus agalactiae and Staphylococcus aureus, in one patient each. We also reviewed the English language literature on PubMed for similar cases. Results: Data on concurrent gout and septic arthritis is limited. Three case series of 14, 25, and 30 patients each where identified. The coexistence of septic arthritis and gout is an infrequent condition. Clinical appearance of the two diseases may be very similar and the presence of monosodium urate (MSU) crystals per se cannot exclude infection. On the other hand, patients with chronic tophaceous gout are prone to infection of MSU tophi and the development of biofilms on the latter may render the eradication of microbes particularly difficult. Vice versa, persistent activation of the immune system fuelled by the infection, together with prolonged hospitalisation and immobilisation, may increase the risk for a gout flare, thus initiating a vicious cycle. Conclusion: In patients with gout, a high index of suspicion for infection is needed by treating physicians, because septic arthritis is a medical emergency which can lead to rapid joint destruction.

Clinical response trajectories and drug persistence in systemic lupus erythematosus patients on belimumab treatment: A real-life, multicentre observational study.

Objective: To obtain real-world data on outcomes of belimumab treatment and respective prognostic factors in patients with systemic lupus erythematosus (SLE). Methods: Observational study of 188 active SLE patients (median disease duration 6.2 years, two previous immunosuppressive/biological agents) treated with belimumab, who were monitored for SLEDAI-2K, Physician Global Assessment (PGA), LLDAS (lupus low disease activity state), remission (DORIS/Padua definitions), SELENA-SLEDAI Flare Index, SLICC/ACR damage index and treatment discontinuations. Group-based disease activity trajectories were modelled followed by multinomial regression for predictive variables. Drug survival was analysed by Cox-regression. Results: At 6, 12 and 24 months, LLDAS was attained by 36.2%, 36.7% and 33.5%, DORIS-remission by 12.3%, 11.6% and 17.8%, and Padua-remission by 21.3%, 17.9% and 29.0%, respectively (attrition-corrected). Trajectory analysis of activity indices classified patients into complete (25.5%), partial (42.0%) and non-responder (32.4%) groups, which were predicted by baseline PGA, inflammatory rash, leukopenia and prior use of mycophenolate. During median follow-up of 15 months, efficacy-related discontinuations occurred in 31.4% of the cohort, especially in patients with higher baseline PGA (hazard ratio [HR] 2.78 per 1-unit; 95% CI 1.32-5.85). Conversely, PGA improvement at 3 months predicted longer drug retention (HR 0.57; 95% CI 0.33-0.97). Use of hydroxychloroquine was associated with lower risk for safety-related drug discontinuation (HR 0.33; 95% CI 0.13-0.85). Although severe flares were reduced, flares were not uncommon (58.0%) and contributed to treatment stops (odds ratio [OR] 1.73 per major flare; 95% CI 1.09-2.75) and damage accrual (OR 1.83 per mild/moderate flare; 95% CI 1.15-2.93). Conclusions: In a real-life setting with predominant long-standing SLE, belimumab was effective in the majority of patients, facilitating the achievement of therapeutic targets. Monitoring PGA helps to identify patients who will likely benefit and stay on the treatment. Vigilance is required for the prevention and management of flares while on belimumab.

Periaortitis and diffuse subendocardial vasculitis in a patient with systemic lupus erythematosus - Lupus flare or a coexisting disease?

Systemic lupus erythematosus (SLE) is a heterogeneous disease with a broad spectrum of clinical manifestations. Periaortitis is a rare disorder which may manifest isolated or in association with other autoimmune diseases, including SLE. Another rare, yet severe cardiovascular manifestation of lupus is diffuse subendocardial vasculitis (DSV), which should be suspected in patients presenting with myocardial hypokinesis, impaired ejection fraction and normal coronary angiography. Cardiovascular Magnetic Resonance (CMR) imaging is crucial to distinguish between DSV and lupus myocarditis, which should also be included in the differential diagnosis. Herein, we describe a case of a female patient with pre-existing SLE, who presented with both periaortitis and DSV, and discuss the diagnostic challenges associated with these rare manifestations.

Pulmonary fibrosis and microscopic polyangiitis in a 75-year-old woman.

We present a case of a 75-year-old woman who admitted in the internal medicine department for a recent onset of persisting moderate daily fever and fatigue that started 30 days prior to her hospitalization. Her past medical history is remarkable for mild pulmonary fibrosis, megaloblastic anaemia, and hypergammaglobulinaemia of no obvious causes. On presentation, she was febrile (38°C) and had high ESR and CRP levels, but most of her laboratory tests were within normal levels and had no signs of arthritis or rash. She was hospitalized for suspected lower urinary tract infection and started on antibiotics. During hospitalization, her renal function deteriorated together with microscopic haematuria, proteinuria and granular urine casts in urine analysis and her inflammation markers raised further. A renal biopsy revealed glomerulonephritis with pauci-immune crescents, and serology tests were positive for anti-MPO p-ANCA, both suggesting a diagnosis of microscopic polyangiitis (MPA). While high-dose methylprednisolone pulses and cyclophosphamide were introduced intravenously, there was no remission, but respiratory failure occurred that led to patient's intubation and transfer to the ICU. She died a few days later due to septic shock. Asymptomatic pulmonary fibrosis can precede microscopic polyangiitis for several years and is associated with a poor prognosis.

The use of Canakinumab in treating resistant gouty disease in patients with limited therapeutic options: The experience of the Rheumatology Clinic of Asklipeion General Hospital of Voula, Greece.

Gout is an autoinflammatory disease caused by monosodium urate mono hydrate crystal deposition in tissues or the supersaturation of extracellular fluids of uric acid. In this study, we are going to report the experience of the Asklepeion Voula Rheumatology Clinic, treating four patients with gouty arthritis who received Canakinumab.

Second high-dose chemotherapy intensification followed by hematopoietic stem cell transplantation applying a novel high-dose topotecan-based regimen in an adult Wilms' tumor patient: case report.

High-dose chemotherapy and hematopoietic stem cell support remains a valuable treatment option for the rare patient population with relapsed Wilms' tumor. Here we report the case of a 22-year-old male patient treated with two cycles of high-dose chemotherapy at relapse after nephrectomy and adjuvant chemotherapy; the first cycle with melphalan--etoposide--carboplatin and the second with a novel preparative regimen incorporating high-dose topotecan (topotecan--cyclophosphamide--melphalan). A detailed discussion and literature review pertaining to that case is provided.

Double high-dose chemotherapy and stem cell transplantation in adult Wilms' tumor.

High-dose chemotherapy intensification and hematopoietic stem cell support remains a valuable treatment option for the rare patient with relapsed Wilms' tumor. We report a 22-year-old adult male with an initially diagnosed stage II Wilms' tumor, treated by nephrectomy followed by adjuvant chemotherapy. After 1 year, an intra-abdominal relapse was treated with salvage ifosfamide carboplatin etoposide chemotherapy followed by autologous hematopoietic stem cell mobilization. It was intended that he would receive two tandem cycles of high-dose chemotherapy; the first consisting of melphalan etoposide carboplatin; however, the patient did not return to receive the second cycle while in remission, but did return later with grossly relapsed disease. He was then treated with a novel preparative regimen incorporating high-dose topotecan (topotecan, melphalan and cyclophosphamide). This case confirms the feasibility of double high-dose chemotherapy with hematopoietic stem cell support in relapsed Wilms' tumor. A detailed discussion with an extensive review of the literature, regarding studies evaluating the role and indications of high-dose chemotherapy in Wilms' tumor is provided.