scholarly journals Colchicine – an effective treatment for children with a clinical diagnosis of autoinflammatory diseases without pathogenic gene variants

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Tatjana Welzel ◽  
Anna L. Wildermuth ◽  
Norbert Deschner ◽  
Susanne M. Benseler ◽  
Jasmin B. Kuemmerle-Deschner

Abstract Background Autoinflammatory diseases (AID) are rare chronic conditions with high disease burden, affecting children and adults. Clinically and genetically confirmed, AID can be effectively treated with targeted cytokine inhibition. In contrast, for patients with clinical AID symptoms without pathogenic gene variants, no treatment recommendations are available. Colchicine is approved and established as effective, safe and low-cost first-line therapy in Familial Mediterranean Fever. Up to now, efficacy data for colchicine in children with a clinical AID diagnosis without pathogenic gene variants are rare. This pilot study was performed to evaluate the effectiveness of colchicine in children with a clinical diagnosis of AID without pathogenic gene variants. Methods A pilot cohort study of consecutive children with active clinical AID without pathogenic gene variants treated with colchicine monotherapy was performed between 01/2009 and 12/2018. Demographics, clinical and laboratory characteristics were determined serially. Colchicine dosing and safety were documented. Physician estimate of disease activity was captured on visual analogue scales (VAS). Primary outcome: Complete response (PGA ≤2 plus CRP ≤0.5 mg/dL and/or SAA ≤10 mg/L) at last follow-up. Secondary outcomes: partial/no response, flare characteristics and requirement for rescue therapies. Analysis: Nonparametric comparison of disease activity measures. Results A total of 33 children were included; 39% were female. Median age at colchicine start was 3.8 years, median follow-up was 14.1 months. Clinical AID diagnoses included CAPS (24%), FMF (27%), PFAPA (43%) and unclassified AID (6%). At baseline, overall disease activity was moderate (PGA 4), inflammatory markers were elevated (CRP 12.1 mg/dL; SAA 289.2 mg/L), and 97% reported febrile flares. Outcome: 55% achieved complete response, 35% showed partial response and 58% had no febrile flares at last follow-up. Inflammatory markers (SAA: p < 0.0001, CRP: p < 0.005) and disease activity (p < 0.0001) decreased significantly. Overall, 93% of children experienced improvement of flare characteristics. Conclusion Colchicine was found to be effective and safe in children with a clinical AID diagnosis in the absence of pathogenic gene variants. Colchicine is a low-cost treatment option for non-organ threatening AID.

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1282-1282
Author(s):  
I. Borges ◽  
T. Barroso ◽  
F. Nunes ◽  
J. Caetano ◽  
B. Grima ◽  
...  

Background:The use of bone scintigraphy (Sc) in spondyloarthritis (SpA) as a technique for diagnosis, assessment of activity and treatment decision has been questioned by the scientific community. Due to its low cost compared to Magnetic Resonance Imaging - MRI (the gold standard)1, some studies proposed to evaluate Sc’s diagnostic accuracy. These studies have shown that Sc has a low diagnostic sensitivity of 50-55%2. Also, there is a poor correlation between symptoms and scintigraphic uptake3. We aimed to evaluate the use of Sc for management and follow-up of patients with SpA.Objectives:To determine if Sc activity correlates with patients’ complaints (peripheral and axial), inflammatory markers, disease activity scores and whether it influenced physicians’ treatment decisions during the follow-up of the disease.Methods:We performed a retrospective review of all patients at our department with SpA with at least one Sc from 2018 to 2020. The following variables were analyzed: demographic data, spondyloarthropathy subtype (ankylosing, enteropathic, psoriatic and undifferentiated SpA), axial or peripheral pain, Sc findings (inflammatory vs no-inflammatory activity), inflammatory markers (sedimentation rate - ESR and C-Reactive Protein - CRP), disease activity scores within one year since the Sc (Ankylosing Spondylitis Disease Activity Score with Erythrocyte Sedimentation Rate - ASDAS-ESR and Bath Ankylosing Spondylitis Disease Activity Index - BASDAI) and treatment at the time of the Sc (non-steroidal anti-inflammatory drugs, conventional synthetic disease-modifying antirheumatic drugs (DMARDs), target synthetic DMARDs and biologic DMARD. Treatment decisions (escalation, de-escalation or maintenance) in accordance to Sc results were also reviewed.We used the non-parametric Mann-Whitney’s U test for comparisons between ordinal or numerical variables. For correlations between categorical variables we used the Fisher’s exact test and the χ2-independence test. Tests with p < 0.05 were statistically significant.Results:Fifty-five patients were reviewed, 75% women; median age of 48 years. Seventy-one percent had ankylosing SpA, 15% enteropathic SpA, 5% psoriatic SpA, 5% undifferentiated and 4% reactive SpA. Sixty-two percent of the patients had both axial and peripheral pain and 24% only axial complaints. Sixty-two percent of the patients had a Sc with no inflammatory changes, 27% had peripheral and 25% had axial inflammatory changes; 15% had evidence of both peripheral and axial inflammation. For ankylosing SpA, the median ASDAS-ESR was 2.89 and according to the BASDAI, 66% had active disease. The median CRP and ESR in patients with inflammatory vs a normal Sc was not different (p=0.02 vs p=0.36, respectively). Similarly, Sc findings were not correlated with patients’ axial (p=0.10) or peripheral pain (p=1.0), neither with the ASDAS-ESR (p=0.29) or the BASDAI (p=0.29). There was no correlation between inflammatory activity in Sc and the decision to maintain, escalate or de-escalate treatment (p=0.65), including the decision to start a biological DMARD (p=1.0) or to switch between biological DMARDs (p=0.19).Conclusion:There was no correlation between Sc findings and ESR, patients’ complaints, disease activity or treatment decisions. Considering previous research showing a low diagnostic sensitivity, our findings seem to support a limited role of bone Sc for the follow-up and management of patients with seronegative SpA.References:[1]Khmelinskii N, Regel A, Baraliakos X. The Role of Imaging in Diagnosing Axial Spondyloarthritis. Front Med. 2018;5. doi:10.3389/fmed.2018.00106[2]Poddubnyy D. Classification vs diagnostic criteria: the challenge of diagnosing axial spondyloarthritis. Rheumatology. 2020;59(Supplement_4):iv6-iv17. doi:10.1093/rheumatology/keaa250[3]Shim JS, Kim C, Ryu JJ, Choi SJ. Correlation between TM joint disease and rheumatic diseases detected on bone scintigraphy and clinical factors. Sci Rep. 2020;10(1):4547. doi:10.1038/s41598-020-60804-xDisclosure of Interests:None declared.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1978-1978
Author(s):  
Jeanne Palmer ◽  
Stephanie J. Lee ◽  
Xiaoyu Chai ◽  
Barry Storer ◽  
Joseph Pidala ◽  
...  

Abstract Abstract 1978 In 2005, a NIH consensus conference was held to better define methods for research in chronic GVHD (cGVHD). Provisional definitions of response categories for individual organs and overall cGVHD disease activity were proposed: complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). These response criteria were designed to improve consistency in documentation of disease activity across different centers, to allow less biased response assessments by comparison of enrollment and follow-up measures, rather than relying on clinician perceptions of change in the setting of clinical trials. In this study, we compared the proposed response criteria with clinician-reported changes in organ specific and overall responses. Good agreement would suggest that the proposed response criteria mirror clinician judgments of whether patients are responding to treatment or not. Methods: Patients ≥ 2 years of age diagnosed with cGVHD requiring systemic treatment ≤ 3 years after transplantation were eligible and assessed every 3–6 months. At each visit, clinicians reported the following: organ specific measures (used to calculate the NIH organ response for skin, mouth, eye and overall), perception of change in organ and overall involvement (completely gone = CR; very much or moderately improved = PR; a little better, stable, or a little worse = SD; or moderately or very much worse = PD), and overall aggregate response (CR, PR, SD, PD). Kappa statistics were used to compare agreement between these measures, with 0.21–0.4 considered fair agreement. Results: As of September 2010, 290 patients who had at least one follow-up visit 3 or 6 months beyond enrollment were included, with median age of 51 years (2–79). Based on NIH overall response criteria, 24 (8%) had CR, 83 (29%) had PR, 25 (9%) had SD, and 158 (54%) had PD for an overall CR+PR of 37%. In contrast, clinicians reported that 31 (11%) had CR, 171 (59%) had PR, 30 (10%) had SD and 56 (19%) had PD for an overall CR+PR of 70%. For organ specific comparisons, agreement rates between NIH proposed response measures and clinician reported changes in skin, mouth and eye were fair. For overall response, agreement rates between the calculated NIH response and clinician-reported overall change and clinician-reported response status were also fair. (Table) Conclusions: For both organ-specific and overall comparisons, the proposed NIH response criteria do not agree well with responses determined by clinicians. These data suggest that conclusions from prior literature reporting high overall CR+PR rates based on clinician judgment would not be supported if the current NIH response criteria had been used to measure response. Additional studies are needed to validate candidate response criteria through correlation with a robust, objective and informative gold standard.Table.Calculated NIH and clinician reported response rates in specific organs and overallOrganResponse measureNNICRPRSDPDKappa with NIH responseSkinCalculated NIH skin response28635%22%7%15%21%Clinician reported skin change28629%17%17%32%5%0.39*/0.43**MouthCalculated NIH mouth response28720%15%7%45%13%Clinician reported mouth change28720%15%29%33%4%0.28*/0.35**EyeCalculated NIH eye response16840%10%4%26%19%Clinician reported eye change16844%2%10%39%5%0.29*/0.26**OverallCalculated NIH overall response288—8%29%9%54%Clinician reported overall change285—7%41%45%8%0.24**Clinician reported response status288—11%59%10%19%0.20**NI, not involved; CR, complete response/completely resolved; PR, partial response/moderately better, very much better; SD, stable disease/a little better/stable/a little worse; PD, progressive disease/moderately worse, very much worse*simple kappa, including all patients**weighted kappa, limited to patients with involvement by both measures at enrollment Disclosures: No relevant conflicts of interest to declare.


Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Kevin F. W Tsoi ◽  
Amit Sahni ◽  
Bianka Selvanayagam ◽  
Muhammad Memon

Abstract Background DAS28 is a measure of disease activity in rheumatoid arthritis (RA) which is comprised of the number of tender and swollen joints, inflammatory markers and visual analogue score. Both NICE and British Society of Rheumatology recommend DAS28 is recorded at least every 6 months in patients with RA, to monitor disease activity and ensure adequate response to treatment. CCG mandate 6 monthly DAS28 scores for patients on high cost DMARDs in order to secure funding. Absence of DAS28 scores results in CCGs refusing to fund treatment at the expense of the Trust. Methods Our aim was to review whether a DAS28 was documented in every consultation and if it meets the audit standard of a review every 6 months. If the 6 month target is not met, to understand the reason for this and to suggest ways to meet the standard. Blueteq is the software used to identify all patients with a diagnosis of RA between January 2014 and January 2019 at Royal Surrey County Hospital (RSCH). Clinic letters were reviewed to identify whether a DAS28 score was recorded, the date it was recorded and whether this was done within 6 months. Results In total, 207 patients are prescribed high cost DMARDs for RA at RSCH. 166 (80%) patients have a documented DAS28, but 41 (20%) patients did not have a documented DAS28. 14 (7%) patients have a documented DAS28 at least 6 monthly. 152 (73%) patients did not meet the audit standard. Conclusion Documentation of DAS28 in clinic letters at RSCH does not meet the audit standard. However, these scores have been recorded on Blueteq in order to satisfy CCG requirements. There needs to be consistency in where DAS28 is recorded. Factors contributing to an absence of a documented DAS28 in clinic letters include: no recent inflammatory markers, patients not receiving clinic appointments scheduled at the correct interval, patients not attending clinic, limited follow-up clinic capacity. DAS28 documentation can be improved by incorporating a table into each rheumatology clinic letter template. On initiation of a high cost therapy, the importance of regular blood monitoring and clinic attendance should be reiterated to patients as well as to the appointments booking team. An early arthritis pathway already exists, which can be extended to incorporate a high cost DMARD pathway detailing how to achieve target documentation. Disclosures: K.F.W. Tsoi: None. A. Sahni: None. B. Selvanayagam: None. M. Memon: None.


MedPharmRes ◽  
2019 ◽  
Vol 3 (3) ◽  
pp. 1-6
Author(s):  
Truc Phan ◽  
Tram Huynh ◽  
Tuan Q. Tran ◽  
Dung Co ◽  
Khoi M. Tran

Introduction: Little information is available on the outcomes of R-CHOP (rituximab with cyclophosphamide, doxorubicin, vincristine and prednisone) and R-CVP (rituximab with cyclophosphamide, vincristine and prednisone) in treatment of the elderly patients with non-Hodgkin lymphoma (NHL), especially in Vietnam. Material and methods: All patients were newly diagnosed with CD20-positive non-Hodgkin lymphoma (NHL) at Blood Transfusion and Hematology Hospital, Ho Chi Minh city (BTH) between 01/2013 and 01/2018 who were age 60 years or older at diagnosis. A retrospective analysis of these patients was perfomed. Results: Twenty-one Vietnamese patients (6 males and 15 females) were identified and the median age was 68.9 (range 60-80). Most of patients have comorbidities and intermediate-risk. The most common sign was lymphadenopathy (over 95%). The proportion of diffuse large B cell lymphoma (DLBCL) was highest (71%). The percentage of patients reaching complete response (CR) after six cycle of chemotherapy was 76.2%. The median follow-up was 26 months, event-free survival (EFS) was 60% and overall survival (OS) was 75%. Adverse effects of rituximab were unremarkable, treatment-related mortality accounted for less than 10%. There was no difference in drug toxicity between two regimens. Conclusions: R-CHOP, R-CVP yielded a good result and acceptable toxicity in treatment of elderly patients with non-Hodgkin lymphoma. In patients with known cardiac history, omission of anthracyclines is reasonable and R-CVP provides a competitive complete response rate.


2018 ◽  
Vol 64 (6) ◽  
pp. 708-715
Author(s):  
Natalya Severskaya ◽  
Andrey Rodichev ◽  
Aleksey Ilin ◽  
Dmitriy Semin ◽  
Pavel Isaev ◽  
...  

Struma ovarii is a rare variant of the mature ovarian teratoma composed of more than 50% thyroid tissue. Thyroid type carcinoma can occur in 5% of struma ovarii. Given the rarity of this pathology, as well as the different clinical course, approaches to the treatment of this disease are controversial. The proposed approaches to treatment vary from ovarian resection to total hysterectomy with bilateral salpingo-oophorectomy and adjuvant therapy. We present here 6 case reports of thyroid type carcinoma in struma ovarii and outcome of patients treated in our clinic. All patients had pelvic surgery of different extent, followed by thyroidectomy and radioiodine therapy. The incidence of metastasis is 67% (4/6), 2 - intraperitoneal metas-tases, 2 - bone metastases. Among patients with metastases, 2 have reached a complete response, one with a good response continues treatment, one had progression. The follow-up period is 1 to 15 years (median 4 years). One patient with follicular carcinoma died of progression 8 years after diagnosis. The remaining patients are alive.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 583-583
Author(s):  
C. Garufi ◽  
F. Ceccarelli ◽  
F. R. Spinelli ◽  
S. Mancuso ◽  
C. Pirone ◽  
...  

Background:In the management of chronic arthritis, such as Rheumatoid Arthritis (RA), Ultrasound (US) assessment can provide relevant information about the joint inflammatory status in the diagnostic phase and even more in the monitoring of disease activity and structural damage1,2.Objectives:In this longitudinal study, we aimed to assesse the role of US in predicting the efficacy of JAK-inhibitors (JAKi) in RA patients.Methods:We enrolled RA patients starting baricitinib or tofacitinib. All patients were evaluated at baseline and after 4, 12, 24, 48 weeks. Disease activity was calculated by DAS28CRP. US examination in 22 joints (I–V MCPs and PIPs, wrists) aimed at evaluating inflammatory features (synovial effusion and hypertrophy, power Doppler-PD), through a semi-quantitative scale (0-3). The total US (0-198) and PD (0-66) scores were calculated. We scanned bilateral flexor (I–V fingers of hands) and extensor compartments (1-6) tendons: tenosynovitis was scored as absent/present (0/1), resulting in a total score (0-22).Results:We studied 102 patients (M/F 15/87; median age 59.2 years, IQR 17.75; median disease duration 144 months, IQR 126), 61 treated with baricitinib and 41 with tofacitinib. At baseline, the median total US score was 18 (IQR 19) and the median PD score 2 (4). We observed a significant reduction in both total and PD US scores at all time-points (p<0.0001) (Figure 1). At baseline, 75.4% of patients showed tenosynovitis involving at least one tendon, with a median score of 2 (IQR 3.5) significantly decreasing after 24 weeks (p=0.02). Multivariate analysis, adjusted for baseline DAS28CRP and other concomitant treatments (including glucocorticoids and methotrexate treatment), confirmed the independent association between baseline US (PD and tenosynovitis) scores and the reduction of disease activity at follow-up evaluations.Conclusion:The present study confirmed the early efficacy of JAKi in RA patients by using US evaluation. Furthermore, power doppler and tenosynovitis scores could play a predictive role in response to treatment.References:[1]MUELLER RB, HASLER C, POPP F, et al. Effectiveness, Tolerability, and Safety of Tofacitinib in Rheumatoid Arthritis: A Retrospective Analysis of Real-World Data from the St. Gallen and Aarau Cohorts. J Clin Med. 2019;8(10):1548.[2]COLEBATCH AN, EDWARDS CJ, ØSTERGAARD M, et al. EULAR recommendations for the use of imaging of the joints in the clinical management of rheumatoid arthritis. Ann Rheum Dis. 2013;72(6):804-14.Figure 1.Ultrasound inflammatory score (a) and Ultrasound Power Doppler (PD) score (b) at baseline and follow-up.Table 1.Baseline characteristics of 414 RA patients.WEEKS04122448US inflammatory score18 (19)11 (15.5)9.5 (11.7)7.5 (8)6 (11)US PD score2 (4)0 (2)0 (1)0 (1)0 (0.7)Disclosure of Interests:Cristina Garufi: None declared, Fulvia Ceccarelli: None declared, Francesca Romana Spinelli Speakers bureau: Abbvie, Eli Lilly, Consultant of: Gilead/Galapagos, Eli Lilly, Grant/research support from: Pfizer, Silvia Mancuso: None declared, Carmelo Pirone: None declared, Fabrizio Conti Speakers bureau: Abbvie, Eli Lilly, Sanofi, Pfizer, Consultant of: Gilead/Galapagos


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