Conclusion: The present targeted NMR based metabolomics study demonstrated that the serum metabol... more Conclusion: The present targeted NMR based metabolomics study demonstrated that the serum metabolic profiles of amino acid may help guide therapy and ratio of Val/Tyr can differentiate active from inactive patients. However, future studies on large patient cohorts are required to establish its clinical utility.
Background: Magnetic resonance imaging (MRI), which has recently become the leading imaging modal... more Background: Magnetic resonance imaging (MRI), which has recently become the leading imaging modality in the study of ankylosing spondylitis (AS), has not been evaluated in the assessment of disease-specific changes at the craniocervical junction (CCJ) in patients with AS. Objectives: To describe the spectrum of active inflammatory lesions at the CCJ using MRI in a cohort of patients with AS and neck pain. Methods: The study included 18 patients with AS presenting with neck pain and a control group of 9 fibromyalgia patients matched for age and levels of neck pain. All patients underwent a focused rheumatologic examination, X-ray of the cervical spine, and a 3T MRI study, which included STIR, CUBE T2, FSE and FSE FAT SAT sequences before and after administration of gadolinium. Results: The median age of AS patients was 43 years with a median disease duration of 7 years. Fifteen of 18 patients were under biologic treatment. Seven of 18 AS patients had evidence of cervical syndesmophytes on X-ray films. Active inflammatory lesions of atlanto-occipital joints and apical and alar ligaments were detected in MRIs in 2 out of the 18 patients with AS and in none of the patients with fibromyalgia. Both AS patients with active inflammation of CCJ detected on MRI received treatment with biological agents prior to and during the study. Conclusions: Active inflammation of both entheses and joints of the CCJ can be demonstrated by MRI in patients with AS.
Purpose: To evaluate the safety and efficacy of fulranumab as adjunct or monotherapy in patients ... more Purpose: To evaluate the safety and efficacy of fulranumab as adjunct or monotherapy in patients with knee or hip pain related to moderate-to-severe osteoarthritis. Methods: Osteoarthritic patients (aged ≥18 years) from 4 phase 3 randomized, double-blind (DB), placebo-controlled studies were randomized to receive placebo, fulranumab 1 mg every 4 weeks (Q4wk), or 3 mg Q4wk in 16-week DB phase, followed by a 52-week posttreatment follow-up phase. Safety assessments included treatment-emergent adverse events (TEAEs), and neurological, sympathetic and joint-related events of interest. Efficacy assessments included pain and physical function subscales of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores. Findings: Of 245 patients from the ITT set (median age, 64 years; women, 62%), 84 (34%) completed DB phase; the majority of discontinuations (57%) were due to early study termination. In DB phase, incidence of TEAEs in fulranumab 3 mg (57.8%) and 1 mg (56.8%) was similar to placebo (56.8%). Two events adjudicated as joint-related events of interest include rapidly progressive osteoarthritis and fracture of unknown etiology. There were no new neurological TEAEs. Fulranumab showed evidence of efficacy in improving pain and physical function based on WOMAC subscales scores. Due to premature study termination, the number of patients enrolled were too small to make any definitive efficacy claims. Implications: Treatment with fulranumab was generally tolerated with no new safety signals. Within the limited sample analyzed, fulranumab showed evidence of improvement of pain and function in patients with moderate-to-severe osteoarthritis who had failed prior therapy and were candidates for joint replacement surgery. Highlights: Key words: Efficacy-Fulranumab-Osteoarthritis of the Hip and Knee-Safety-WOMAC Scores • Fulranumab as adjuvant or monotherapy was well tolerated with no new safety signals • Fulranumab demonstrated evidence suggestive of efficacy in osteoarthritic pain of hip and knee • Fulranumab demonstrated evidence suggestive of improvement of pain and physical function in osteoarthritis
Background Familial Mediterranean Fever (FMF) is an autoinflammatory disease characterized by rec... more Background Familial Mediterranean Fever (FMF) is an autoinflammatory disease characterized by recurrent attacks of fever and serositis. A relation between FMF and Ankylosing Spondylitis (AS) has been suggested in small cohort studies, although there is no consensus regarding the role of HLA B27. Colchicine, the mainstay treatment in FMF, does not improve the axial or peripheral symptoms due to spondylarthropathy. There are controversial data about the efficacy of Tumor Necrosis Factor Alpha (TNF α) blockade in FMF patients (1). Objectives Efficacity of Tumor Necrosis Factor Alpha in FMF patients with axial spondyloarthropathy. Methods We report our experience in 4 patients with intractable FMF treated with oral colchicine and supplemental IV colchicine (2), that were treated with TNF α blockade for symptomatic axial spondylarthropathy). Results A 26- year-a old man with MEFV mutations V726A and E148Q, negative for HLAB27, with concomitant ulcerative colitis was treated with infliximab and then with adalimumab; and 3 women (42, 48 and 55 years old), two of them treated with infliximab and one treated with adalimumab. The three women were homozygous for the M694V mutation. All developed severe to moderate adverse events: exacerbation of FMF in 2 of them, and myositis and ulcerative colitis exacerbation in the male patient, and staphylococcus aureus sepsis in another patient. Three of them had to stop the TNF α blockade treatment. One patient developed psoriatic rash, with no need to stop the treatment. Conclusions In our limited experience, TNF α blockade in patients with both intractable FMF and AS is not very effective and may be associated with severe adverse events. Little is known about the possible interaction between intravenous colchicine and anti-TNF treatment. References Bilgen SA, Kilic L, Akdogan A, Kiraz S, Kalyoncu U, Karadag O, Ertenli I, Dogan I, Calguneri M. Effects of anti-tumor necrosis factors agents for familial Mediterranean fever patients with chronic arthritis and/or sacroiliitis who were resistant to colchicine treatment. J clin Rheumatol 2011;7:358-62. Rozenbaum M, Boulman N, Feld J, Avshovich N, Petrovich S, Elias M, Slobodin G, Rosner I. Intravenous colchicine treatment for six months: adjunctive therapy in Familial Mediterranean fever (FMF) unresponsive to oral colchicine. Clin Exp Rheumatol 2009; 27 (2 suppl 53) S 105. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1994
Clinical and Experimental Rheumatology, Oct 6, 2021
Objective. To evaluate the effect of canakinumab on health-related quality of life (HRQoL), work/... more Objective. To evaluate the effect of canakinumab on health-related quality of life (HRQoL), work/school and social life of patients with autoinflammatory recurrent fever syndromes, including colchicine-resistant familial Mediterranean fever, mevalonate kinase deficiency, and tumour necrosis factor receptor-associated periodic syndrome, in the CLUSTER trial. Methods. HRQoL of patients who received canakinumab 150 mg or 300 mg every four weeks in the CLUSTER trial (n=173) was assessed at baseline and Weeks 17 and 41. For children we used the Child Health Questionnaire-Parent Form 50 (CHQ-PF50), including psychosocial (PsS) and physical (PhS) component summary scores. For adults, the Short-Form-12 (SF-12) Health Survey was used, including physical (PFS) and mental (PCS) component summary scores. The Sheehan Disability Scale (SDS) was used to determine the impact of treatment on work/school, social and family life. Results. The results obtained were remarkably consistent in both paediatric and adult patients across the three disease cohorts. At baseline, median scores for physical components were relatively low (26-29 for PhS and 34-38 for PFS); they improved to values similar to those expected in the general population by Week 17, and this improvement was sustained at Week 41, when median PhS scores were 47-50 and PFS 44-54. Psychosocial and mental scores also improved from baseline to Week 17 and 41, with scores comparable to the general population. Notable improvements were also observed in the SDS scale. Conclusion. Patients with three inherited autoinflammatory syndromes experienced sustained improvements on their HRQoL, work/school, and social life on treatment with canakinumab.
Background: Musculoskeletal ultrasonography (US) is one of the standard tools for the diagnosis a... more Background: Musculoskeletal ultrasonography (US) is one of the standard tools for the diagnosis and monitoring of rheumatoid arthritis (RA). Although we and other groups have proposed several sets of US assessment procedures in arbitrary combinations of selected joints, 1-3 there is still no consensus in defining the joints to evaluate. Objectives: To investigate whether US assessment in the selected 8 joints which we advocate as a routine assessment is useful for monitoring response to treatment for RA. Methods: Power Doppler (PD) US was performed in 24 joints, including all PIP, MCP, bilateral wrist and knee joints, as comprehensive evaluation in 15 RA patients treated with certolizumab pegol (CZP). Before and after treatment with CZP, PD signals were scored semiquantitatively from 0 to 3 in each joint, and total PD oscore-24 and total PD score-8 were calculated by summing up PD scores of the 24 joints and the selected 8 joints (bilateral second and third MCP, wrist, and knee joints), respectively. 1 Results: Amount of change of total PD score-24 by treatment with CZP correlated highly with the changes of disease activity indices, SDAI (r s =0.91, p <0.01) and DAS28-CRP (r s =0.86, p <0.01). Although it correlated well with the changes of some components of disease activity indices, including swollen joint count (r s =0.74, p <0.01), tender joint count (r s =0.86, p <0.01), CRP (r s =0.85, p <0.01) and ESR (r s =0.62, p <0.01), there were no significant correlations between the changes of total PD score-24 and the changes of patient's global assessment (r s =0.42, p >0.05) and evaluator's global assessment (r s =0.27, p >0.05). Amount of change of total PD score-8 exhibited stronger correlations with the changes of SDAI (r s =0.92, p <0.01) and DAS28-CRP (r s =0.89, p <0.01) as compared to that of total PD score-24 (Figure 1). The change of total PD score-8 correlated more highly with the changes of swollen joint count (r s =0.81, p <0.01) and tender joint count (r s =0.91, p <0.01), while it showed lower correlation coefficients with the changes of patient's global assessment (r s =0.39, p >0.05) and evaluator's global assessment (r s =0.22, p >0.05) as compared to that of total PD score-24. Conclusions: This study suggests that total PD score-8 is useful for monitoring response to treatment in RA patients. References: [1] Yoshimi R, Ihata A, Kunishita Y, et al. A novel 8-joint ultrasound score is useful in daily practice for rheumatoid arthritis.
Journal of scleroderma and related disorders, May 28, 2021
Systemic sclerosis (SSc) is an autoimmune disease in which environmental exposure to substances a... more Systemic sclerosis (SSc) is an autoimmune disease in which environmental exposure to substances and agents may trigger disease onset or exacerbation. The most fatal complication of SSc is scleroderma renal crisis (SRC), the incidence of which is 2-3%. SRC usually occurs in the first 5 years from disease onset in diffuse-SSc patients with anti-topoisomerase 1 (ATA) or RNA polymerase 3 antibodies [1]. Other risk factors for SRC are pericardial effusion, tendon friction rub and steroid use. We report herein a case of scleroderma renal crisis (SRC), following covid-19 infection, in a limited-SSc patient who was in long remission prior to the infection without any risk factors for SRC. the temporal relationship and lack of other risk factors combine to suggest covid-19 infection as a possible trigger for SRC. We discuss the shared pathophysiology of covid-19 infection and SRC, including, vasculopathy, endothelial activation, hypercoagulability, cytokines release as interleukin 6, that may explain the possible role of covid-19 infection, as a trigger for SRC in SSc patients.
ObjectiveThis phase 3 study was undertaken to investigate the efficacy and safety of lenabasum, a... more ObjectiveThis phase 3 study was undertaken to investigate the efficacy and safety of lenabasum, a cannabinoid type 2 receptor agonist, in patients with diffuse cutaneous systemic sclerosis (dcSSc).MethodsA multinational double‐blind study was conducted in 365 dcSSc patients who were randomized and dosed 1:1:1 with lenabasum 20 mg, lenabasum 5 mg, or placebo, each twice daily and added to background treatments, including immunosuppressive therapies (IST).ResultsThe primary end point, the American College of Rheumatology combined response index in dcSSc (CRISS) at week 52 for lenabasum 20 mg twice a day versus placebo, was not met, with CRISS score of 0.888 versus 0.887 (P = 0.4972, using mixed models repeated measures [MMRM]). The change in the modified Rodnan skin thickness score (MRSS) at week 52 for lenabasum 20 mg twice a day versus placebo was −6.7 versus −8.1 (P = 0.1183, using MMRM). Prespecified analyses showed higher CRISS scores, greater improvement in MRSS, and lower decli...
BackgroundAutologous hematological stem cell transplantation (AHSCT) is a grade A therapy for ear... more BackgroundAutologous hematological stem cell transplantation (AHSCT) is a grade A therapy for early diffuse progressive systemic sclerosis (SSc), that has been validated in three randomized controlled trials (RCT) compared to cyclophosphamide (CYC) [1]. CYC, however, is no longer considered the gold standard therapy for SSc and does not provide long-term benefit [2]. The efficacy of rituximab on skin and lung involvement in SSc has recently been demonstrated in an RCT, the DESIRES study. The combination of rituximab with mycophenolate mofetil (MMF) is a potential potent regimen for progressive SSc, that has not been evaluated compared to AHSCT.ObjectivesTo retrospectively compare the outcomes of SSc patients in our cohort, fulfilling eligibility criteria for AHSCT studies, who received a combination therapy of MMF and rituximab, with patients who underwent AHSCT.MethodsRepeated longitudinal assessments at baseline and every 6 months for 24 months, including modified Rodnan Skin Scor...
Background:Elevated serum levels of interleukin (IL)-22 were reported in patients with ankylosing... more Background:Elevated serum levels of interleukin (IL)-22 were reported in patients with ankylosing spondylitis (AS).[1]IL-22 was also reported to drive the osteogenic differentiation of mesenchymal stem cells.[2]Objectives:To confirm the fact that serum levels of IL-22 are elevated in AS patients and to examine the relationship between concentrations of IL-22 and degree of radiographic progression in AS patients.Methods:Seventeen male patients with established AS of more than 4 years duration signed the informed consent and donated 10 ml of peripheral blood. Demographic data was collected from patient’s charts. Disease activity indices were calculated for all patients and radiographic disease progression was calculated as mSASS. A control group included 6 healthy persons and 4 patients with advanced diffuse idiopathic skeletal hyperostosis (DISH). Serum levels of IL-22 were tested using enzyme-linked immunosorbent assay. Intergroup differences were examined using the Mann-Whitney tes...
The Israel Medical Association journal : IMAJ, 2019
C apillaroscopy is a non-invasive, diagnostic tool designed to enable clinicians to evaluate micr... more C apillaroscopy is a non-invasive, diagnostic tool designed to enable clinicians to evaluate microcirculation. In 1663, Johan Christophorous Kolhaus was the first clinician to use a primitive microscope to observe the small blood vessels surrounding the nails. Giovanni Rasori (1776–1873), using a magnifying glass, first reported the close relationship between conjunctival inflammation and the presence of an inextricable knot of capillaries [1]. In 1862, Maurice Raynaud (1834–1881) presented his thesis in Paris on local ischemic damage of the hands, feet, nose, and tongue that became the early crucial vascular signs of several autoimmune diseases and was named “Raynaud’s phenomena” [2]. In 1911, W.P. Lombard discovered that using a microscope, after the application of a drop of immersion oil, periungual capillaries could be observed in humans [3]. In 1916, W. Weiss standardized the capillaroscopic technique and was able to take pictures of the capillaries using a primordial camera. F...
Background: Immune semaphorins are important players in controlling both innate and adaptive immu... more Background: Immune semaphorins are important players in controlling both innate and adaptive immune responses. The regulatory role of semaphorin3A (sema3A) in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and other autoimmune diseases is widely reported. Decreased levels of serum sema3A were shown to be associated with SLE disease activity. Objectives: To assess urine concentrations of sema3A in SLE patients and its correlation with renal involvement and disease activity. Methods: Urine levels of sema3A were analyzed in 38 SLE patients of whom 13 had renal involvement and were compared to 10 healthy controls and 8 RA patients (disease control group). Results: The secretion of urine sema3A was found to be signi cantly lower in SLE patients compared to healthy controls and RA patients (4.9±3.9 ng/ml, 8.5±2.7 ng/ml, 9.85±1.7 ng/ml, respectively, p = 0.0006). Urine sema3A was signi cantly lower in SLE patients with lupus nephritis than in patients without nephritis (4.0±3.4 ng/ml vs 6.5±3.8 ng/ml, p=0.03). Urine sema3A was inversely correlated with proteinuria and SLE disease activity. Conclusion: Urine sema3A is decreased in lupus patients and should be further evaluated as a possible biomarker for disease activity and renal involvement.
Objective Crowned dens syndrome (CDS) is defined as acute cervical or occipital pain due to a loc... more Objective Crowned dens syndrome (CDS) is defined as acute cervical or occipital pain due to a local inflammatory reaction related to calcifications in the ligaments surrounding the odontoid process. Virtually, all previous descriptions of CDS have related to calcium pyrophosphate dehydrate (CPPD) arthropathy. Methods We prospectively identified a total of twenty-four consecutive inpatients with Crowned dens syndrome from January 2016 to December 2017 in our institution. Results All patients (age range 54 to 87 years, 67% females) presented with acute onset pain in the upper neck and/or occiput accompanied with extreme neck stiffness. Most patients (79%) had elevated inflammatory markers. Four patients underwent temporal artery biopsy, which was negative for arteritis in all cases, and one was subjected to lumbar puncture, which was noncontributory. Seventeen patients (71%) had known rheumatic disease on presentation: 10 patients had the diagnosis of calcium pyrophosphate dehydrate arthropathy, 3 patients had ankylosing spondylitis, 2 patients had rheumatoid arthritis, 1 patient had Behcet's disease, and 1 suffered from Familial Mediterranean Fever. In 4 more patients, crowned dens syndrome was the presenting symptom of calcium pyrophosphate dehydrate disease. All patients were treated with glucocorticoids as 0.5 mg/kg prednisone plus colchicine 0.5 mg bid resulting in dramatic improvement in both clinical (head/neck pain alleviated and cervical spinal mobility regained) and laboratory measures. Conclusions Crowned dens syndrome should be considered, and craniocervical junction imaged in the context of acute cervical or occipital pain with stiffness and elevated inflammation markers not only in patients previously diagnosed with calcium pyrophosphate dehydrate arthropathy but also in diverse clinical settings. Key Points • This report highlights that crowned dens syndrome should be considered in various clinical setting besides calcium pyrophosphate dehydrate (CPPD) arthropathy. • Vigilance to this syndrome allows rapid treatment and may spare the patient unnecessary invasive procedures (i.e., temporal artery biopsy or lumbar puncture).
Conclusion: The present targeted NMR based metabolomics study demonstrated that the serum metabol... more Conclusion: The present targeted NMR based metabolomics study demonstrated that the serum metabolic profiles of amino acid may help guide therapy and ratio of Val/Tyr can differentiate active from inactive patients. However, future studies on large patient cohorts are required to establish its clinical utility.
Background: Magnetic resonance imaging (MRI), which has recently become the leading imaging modal... more Background: Magnetic resonance imaging (MRI), which has recently become the leading imaging modality in the study of ankylosing spondylitis (AS), has not been evaluated in the assessment of disease-specific changes at the craniocervical junction (CCJ) in patients with AS. Objectives: To describe the spectrum of active inflammatory lesions at the CCJ using MRI in a cohort of patients with AS and neck pain. Methods: The study included 18 patients with AS presenting with neck pain and a control group of 9 fibromyalgia patients matched for age and levels of neck pain. All patients underwent a focused rheumatologic examination, X-ray of the cervical spine, and a 3T MRI study, which included STIR, CUBE T2, FSE and FSE FAT SAT sequences before and after administration of gadolinium. Results: The median age of AS patients was 43 years with a median disease duration of 7 years. Fifteen of 18 patients were under biologic treatment. Seven of 18 AS patients had evidence of cervical syndesmophytes on X-ray films. Active inflammatory lesions of atlanto-occipital joints and apical and alar ligaments were detected in MRIs in 2 out of the 18 patients with AS and in none of the patients with fibromyalgia. Both AS patients with active inflammation of CCJ detected on MRI received treatment with biological agents prior to and during the study. Conclusions: Active inflammation of both entheses and joints of the CCJ can be demonstrated by MRI in patients with AS.
Purpose: To evaluate the safety and efficacy of fulranumab as adjunct or monotherapy in patients ... more Purpose: To evaluate the safety and efficacy of fulranumab as adjunct or monotherapy in patients with knee or hip pain related to moderate-to-severe osteoarthritis. Methods: Osteoarthritic patients (aged ≥18 years) from 4 phase 3 randomized, double-blind (DB), placebo-controlled studies were randomized to receive placebo, fulranumab 1 mg every 4 weeks (Q4wk), or 3 mg Q4wk in 16-week DB phase, followed by a 52-week posttreatment follow-up phase. Safety assessments included treatment-emergent adverse events (TEAEs), and neurological, sympathetic and joint-related events of interest. Efficacy assessments included pain and physical function subscales of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores. Findings: Of 245 patients from the ITT set (median age, 64 years; women, 62%), 84 (34%) completed DB phase; the majority of discontinuations (57%) were due to early study termination. In DB phase, incidence of TEAEs in fulranumab 3 mg (57.8%) and 1 mg (56.8%) was similar to placebo (56.8%). Two events adjudicated as joint-related events of interest include rapidly progressive osteoarthritis and fracture of unknown etiology. There were no new neurological TEAEs. Fulranumab showed evidence of efficacy in improving pain and physical function based on WOMAC subscales scores. Due to premature study termination, the number of patients enrolled were too small to make any definitive efficacy claims. Implications: Treatment with fulranumab was generally tolerated with no new safety signals. Within the limited sample analyzed, fulranumab showed evidence of improvement of pain and function in patients with moderate-to-severe osteoarthritis who had failed prior therapy and were candidates for joint replacement surgery. Highlights: Key words: Efficacy-Fulranumab-Osteoarthritis of the Hip and Knee-Safety-WOMAC Scores • Fulranumab as adjuvant or monotherapy was well tolerated with no new safety signals • Fulranumab demonstrated evidence suggestive of efficacy in osteoarthritic pain of hip and knee • Fulranumab demonstrated evidence suggestive of improvement of pain and physical function in osteoarthritis
Background Familial Mediterranean Fever (FMF) is an autoinflammatory disease characterized by rec... more Background Familial Mediterranean Fever (FMF) is an autoinflammatory disease characterized by recurrent attacks of fever and serositis. A relation between FMF and Ankylosing Spondylitis (AS) has been suggested in small cohort studies, although there is no consensus regarding the role of HLA B27. Colchicine, the mainstay treatment in FMF, does not improve the axial or peripheral symptoms due to spondylarthropathy. There are controversial data about the efficacy of Tumor Necrosis Factor Alpha (TNF α) blockade in FMF patients (1). Objectives Efficacity of Tumor Necrosis Factor Alpha in FMF patients with axial spondyloarthropathy. Methods We report our experience in 4 patients with intractable FMF treated with oral colchicine and supplemental IV colchicine (2), that were treated with TNF α blockade for symptomatic axial spondylarthropathy). Results A 26- year-a old man with MEFV mutations V726A and E148Q, negative for HLAB27, with concomitant ulcerative colitis was treated with infliximab and then with adalimumab; and 3 women (42, 48 and 55 years old), two of them treated with infliximab and one treated with adalimumab. The three women were homozygous for the M694V mutation. All developed severe to moderate adverse events: exacerbation of FMF in 2 of them, and myositis and ulcerative colitis exacerbation in the male patient, and staphylococcus aureus sepsis in another patient. Three of them had to stop the TNF α blockade treatment. One patient developed psoriatic rash, with no need to stop the treatment. Conclusions In our limited experience, TNF α blockade in patients with both intractable FMF and AS is not very effective and may be associated with severe adverse events. Little is known about the possible interaction between intravenous colchicine and anti-TNF treatment. References Bilgen SA, Kilic L, Akdogan A, Kiraz S, Kalyoncu U, Karadag O, Ertenli I, Dogan I, Calguneri M. Effects of anti-tumor necrosis factors agents for familial Mediterranean fever patients with chronic arthritis and/or sacroiliitis who were resistant to colchicine treatment. J clin Rheumatol 2011;7:358-62. Rozenbaum M, Boulman N, Feld J, Avshovich N, Petrovich S, Elias M, Slobodin G, Rosner I. Intravenous colchicine treatment for six months: adjunctive therapy in Familial Mediterranean fever (FMF) unresponsive to oral colchicine. Clin Exp Rheumatol 2009; 27 (2 suppl 53) S 105. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1994
Clinical and Experimental Rheumatology, Oct 6, 2021
Objective. To evaluate the effect of canakinumab on health-related quality of life (HRQoL), work/... more Objective. To evaluate the effect of canakinumab on health-related quality of life (HRQoL), work/school and social life of patients with autoinflammatory recurrent fever syndromes, including colchicine-resistant familial Mediterranean fever, mevalonate kinase deficiency, and tumour necrosis factor receptor-associated periodic syndrome, in the CLUSTER trial. Methods. HRQoL of patients who received canakinumab 150 mg or 300 mg every four weeks in the CLUSTER trial (n=173) was assessed at baseline and Weeks 17 and 41. For children we used the Child Health Questionnaire-Parent Form 50 (CHQ-PF50), including psychosocial (PsS) and physical (PhS) component summary scores. For adults, the Short-Form-12 (SF-12) Health Survey was used, including physical (PFS) and mental (PCS) component summary scores. The Sheehan Disability Scale (SDS) was used to determine the impact of treatment on work/school, social and family life. Results. The results obtained were remarkably consistent in both paediatric and adult patients across the three disease cohorts. At baseline, median scores for physical components were relatively low (26-29 for PhS and 34-38 for PFS); they improved to values similar to those expected in the general population by Week 17, and this improvement was sustained at Week 41, when median PhS scores were 47-50 and PFS 44-54. Psychosocial and mental scores also improved from baseline to Week 17 and 41, with scores comparable to the general population. Notable improvements were also observed in the SDS scale. Conclusion. Patients with three inherited autoinflammatory syndromes experienced sustained improvements on their HRQoL, work/school, and social life on treatment with canakinumab.
Background: Musculoskeletal ultrasonography (US) is one of the standard tools for the diagnosis a... more Background: Musculoskeletal ultrasonography (US) is one of the standard tools for the diagnosis and monitoring of rheumatoid arthritis (RA). Although we and other groups have proposed several sets of US assessment procedures in arbitrary combinations of selected joints, 1-3 there is still no consensus in defining the joints to evaluate. Objectives: To investigate whether US assessment in the selected 8 joints which we advocate as a routine assessment is useful for monitoring response to treatment for RA. Methods: Power Doppler (PD) US was performed in 24 joints, including all PIP, MCP, bilateral wrist and knee joints, as comprehensive evaluation in 15 RA patients treated with certolizumab pegol (CZP). Before and after treatment with CZP, PD signals were scored semiquantitatively from 0 to 3 in each joint, and total PD oscore-24 and total PD score-8 were calculated by summing up PD scores of the 24 joints and the selected 8 joints (bilateral second and third MCP, wrist, and knee joints), respectively. 1 Results: Amount of change of total PD score-24 by treatment with CZP correlated highly with the changes of disease activity indices, SDAI (r s =0.91, p <0.01) and DAS28-CRP (r s =0.86, p <0.01). Although it correlated well with the changes of some components of disease activity indices, including swollen joint count (r s =0.74, p <0.01), tender joint count (r s =0.86, p <0.01), CRP (r s =0.85, p <0.01) and ESR (r s =0.62, p <0.01), there were no significant correlations between the changes of total PD score-24 and the changes of patient's global assessment (r s =0.42, p >0.05) and evaluator's global assessment (r s =0.27, p >0.05). Amount of change of total PD score-8 exhibited stronger correlations with the changes of SDAI (r s =0.92, p <0.01) and DAS28-CRP (r s =0.89, p <0.01) as compared to that of total PD score-24 (Figure 1). The change of total PD score-8 correlated more highly with the changes of swollen joint count (r s =0.81, p <0.01) and tender joint count (r s =0.91, p <0.01), while it showed lower correlation coefficients with the changes of patient's global assessment (r s =0.39, p >0.05) and evaluator's global assessment (r s =0.22, p >0.05) as compared to that of total PD score-24. Conclusions: This study suggests that total PD score-8 is useful for monitoring response to treatment in RA patients. References: [1] Yoshimi R, Ihata A, Kunishita Y, et al. A novel 8-joint ultrasound score is useful in daily practice for rheumatoid arthritis.
Journal of scleroderma and related disorders, May 28, 2021
Systemic sclerosis (SSc) is an autoimmune disease in which environmental exposure to substances a... more Systemic sclerosis (SSc) is an autoimmune disease in which environmental exposure to substances and agents may trigger disease onset or exacerbation. The most fatal complication of SSc is scleroderma renal crisis (SRC), the incidence of which is 2-3%. SRC usually occurs in the first 5 years from disease onset in diffuse-SSc patients with anti-topoisomerase 1 (ATA) or RNA polymerase 3 antibodies [1]. Other risk factors for SRC are pericardial effusion, tendon friction rub and steroid use. We report herein a case of scleroderma renal crisis (SRC), following covid-19 infection, in a limited-SSc patient who was in long remission prior to the infection without any risk factors for SRC. the temporal relationship and lack of other risk factors combine to suggest covid-19 infection as a possible trigger for SRC. We discuss the shared pathophysiology of covid-19 infection and SRC, including, vasculopathy, endothelial activation, hypercoagulability, cytokines release as interleukin 6, that may explain the possible role of covid-19 infection, as a trigger for SRC in SSc patients.
ObjectiveThis phase 3 study was undertaken to investigate the efficacy and safety of lenabasum, a... more ObjectiveThis phase 3 study was undertaken to investigate the efficacy and safety of lenabasum, a cannabinoid type 2 receptor agonist, in patients with diffuse cutaneous systemic sclerosis (dcSSc).MethodsA multinational double‐blind study was conducted in 365 dcSSc patients who were randomized and dosed 1:1:1 with lenabasum 20 mg, lenabasum 5 mg, or placebo, each twice daily and added to background treatments, including immunosuppressive therapies (IST).ResultsThe primary end point, the American College of Rheumatology combined response index in dcSSc (CRISS) at week 52 for lenabasum 20 mg twice a day versus placebo, was not met, with CRISS score of 0.888 versus 0.887 (P = 0.4972, using mixed models repeated measures [MMRM]). The change in the modified Rodnan skin thickness score (MRSS) at week 52 for lenabasum 20 mg twice a day versus placebo was −6.7 versus −8.1 (P = 0.1183, using MMRM). Prespecified analyses showed higher CRISS scores, greater improvement in MRSS, and lower decli...
BackgroundAutologous hematological stem cell transplantation (AHSCT) is a grade A therapy for ear... more BackgroundAutologous hematological stem cell transplantation (AHSCT) is a grade A therapy for early diffuse progressive systemic sclerosis (SSc), that has been validated in three randomized controlled trials (RCT) compared to cyclophosphamide (CYC) [1]. CYC, however, is no longer considered the gold standard therapy for SSc and does not provide long-term benefit [2]. The efficacy of rituximab on skin and lung involvement in SSc has recently been demonstrated in an RCT, the DESIRES study. The combination of rituximab with mycophenolate mofetil (MMF) is a potential potent regimen for progressive SSc, that has not been evaluated compared to AHSCT.ObjectivesTo retrospectively compare the outcomes of SSc patients in our cohort, fulfilling eligibility criteria for AHSCT studies, who received a combination therapy of MMF and rituximab, with patients who underwent AHSCT.MethodsRepeated longitudinal assessments at baseline and every 6 months for 24 months, including modified Rodnan Skin Scor...
Background:Elevated serum levels of interleukin (IL)-22 were reported in patients with ankylosing... more Background:Elevated serum levels of interleukin (IL)-22 were reported in patients with ankylosing spondylitis (AS).[1]IL-22 was also reported to drive the osteogenic differentiation of mesenchymal stem cells.[2]Objectives:To confirm the fact that serum levels of IL-22 are elevated in AS patients and to examine the relationship between concentrations of IL-22 and degree of radiographic progression in AS patients.Methods:Seventeen male patients with established AS of more than 4 years duration signed the informed consent and donated 10 ml of peripheral blood. Demographic data was collected from patient’s charts. Disease activity indices were calculated for all patients and radiographic disease progression was calculated as mSASS. A control group included 6 healthy persons and 4 patients with advanced diffuse idiopathic skeletal hyperostosis (DISH). Serum levels of IL-22 were tested using enzyme-linked immunosorbent assay. Intergroup differences were examined using the Mann-Whitney tes...
The Israel Medical Association journal : IMAJ, 2019
C apillaroscopy is a non-invasive, diagnostic tool designed to enable clinicians to evaluate micr... more C apillaroscopy is a non-invasive, diagnostic tool designed to enable clinicians to evaluate microcirculation. In 1663, Johan Christophorous Kolhaus was the first clinician to use a primitive microscope to observe the small blood vessels surrounding the nails. Giovanni Rasori (1776–1873), using a magnifying glass, first reported the close relationship between conjunctival inflammation and the presence of an inextricable knot of capillaries [1]. In 1862, Maurice Raynaud (1834–1881) presented his thesis in Paris on local ischemic damage of the hands, feet, nose, and tongue that became the early crucial vascular signs of several autoimmune diseases and was named “Raynaud’s phenomena” [2]. In 1911, W.P. Lombard discovered that using a microscope, after the application of a drop of immersion oil, periungual capillaries could be observed in humans [3]. In 1916, W. Weiss standardized the capillaroscopic technique and was able to take pictures of the capillaries using a primordial camera. F...
Background: Immune semaphorins are important players in controlling both innate and adaptive immu... more Background: Immune semaphorins are important players in controlling both innate and adaptive immune responses. The regulatory role of semaphorin3A (sema3A) in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and other autoimmune diseases is widely reported. Decreased levels of serum sema3A were shown to be associated with SLE disease activity. Objectives: To assess urine concentrations of sema3A in SLE patients and its correlation with renal involvement and disease activity. Methods: Urine levels of sema3A were analyzed in 38 SLE patients of whom 13 had renal involvement and were compared to 10 healthy controls and 8 RA patients (disease control group). Results: The secretion of urine sema3A was found to be signi cantly lower in SLE patients compared to healthy controls and RA patients (4.9±3.9 ng/ml, 8.5±2.7 ng/ml, 9.85±1.7 ng/ml, respectively, p = 0.0006). Urine sema3A was signi cantly lower in SLE patients with lupus nephritis than in patients without nephritis (4.0±3.4 ng/ml vs 6.5±3.8 ng/ml, p=0.03). Urine sema3A was inversely correlated with proteinuria and SLE disease activity. Conclusion: Urine sema3A is decreased in lupus patients and should be further evaluated as a possible biomarker for disease activity and renal involvement.
Objective Crowned dens syndrome (CDS) is defined as acute cervical or occipital pain due to a loc... more Objective Crowned dens syndrome (CDS) is defined as acute cervical or occipital pain due to a local inflammatory reaction related to calcifications in the ligaments surrounding the odontoid process. Virtually, all previous descriptions of CDS have related to calcium pyrophosphate dehydrate (CPPD) arthropathy. Methods We prospectively identified a total of twenty-four consecutive inpatients with Crowned dens syndrome from January 2016 to December 2017 in our institution. Results All patients (age range 54 to 87 years, 67% females) presented with acute onset pain in the upper neck and/or occiput accompanied with extreme neck stiffness. Most patients (79%) had elevated inflammatory markers. Four patients underwent temporal artery biopsy, which was negative for arteritis in all cases, and one was subjected to lumbar puncture, which was noncontributory. Seventeen patients (71%) had known rheumatic disease on presentation: 10 patients had the diagnosis of calcium pyrophosphate dehydrate arthropathy, 3 patients had ankylosing spondylitis, 2 patients had rheumatoid arthritis, 1 patient had Behcet's disease, and 1 suffered from Familial Mediterranean Fever. In 4 more patients, crowned dens syndrome was the presenting symptom of calcium pyrophosphate dehydrate disease. All patients were treated with glucocorticoids as 0.5 mg/kg prednisone plus colchicine 0.5 mg bid resulting in dramatic improvement in both clinical (head/neck pain alleviated and cervical spinal mobility regained) and laboratory measures. Conclusions Crowned dens syndrome should be considered, and craniocervical junction imaged in the context of acute cervical or occipital pain with stiffness and elevated inflammation markers not only in patients previously diagnosed with calcium pyrophosphate dehydrate arthropathy but also in diverse clinical settings. Key Points • This report highlights that crowned dens syndrome should be considered in various clinical setting besides calcium pyrophosphate dehydrate (CPPD) arthropathy. • Vigilance to this syndrome allows rapid treatment and may spare the patient unnecessary invasive procedures (i.e., temporal artery biopsy or lumbar puncture).
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Papers by Itzhak Rosner