Factors Associated With Inadequate Response to Bisphosphonate Therapy in Patients With Osteoporosis in Real-Life Clinical Practice: a Single-Center Retrospective Analysis of 300 Patients

Abstract Introduction: Bone mineral density (BMD) measurement by dual X-ray absorptiometry (DXA) is a useful tool to monitor response to osteoporosis treatment in clinical practice. Despite bisphosphonates therapy, some patients may exhibit bone loss during treatment for different reasons. These patients may have greater fracture risk than responders and may have unrecognized secondary causes that require further attention and treatment. Objectives: To identify factors associated with inadequate response (IR) to bisphosphonates therapy in patients with osteoporosis in real-life clinical practice. Methods: This is a single-center case-control study of patients with osteoporosis treated with bisphosphonates as recommended. Baseline and follow-up (12–24 months/apart) DXA scans were performed on same device (GE-Lunar Prodigy). IR was defined as loss of BMD greater than the least significant change (LSC) on the follow-up DXA. Clinical, biochemical and densitometric parameters of patients with IR were compared to responders using t-test or Mann-Whitney test (continuous), or chi-square test (categorical variables), as appropriated. We used logistic regression to assess the association magnitude between exposures and IR. Results: From 300 patients included from 2014 to 2018 (13% males, mean age 68 ±10 years), 198(66%) were treated with oral bisphosphonates and 102(34%) with zoledronic acid (ZA). IR was observed in 44(15%) patients. All parameters were similar at baseline, except for greater prevalence of oral bisphosphonates (82% vs 63%, p=0.016) and anticonvulsants use (18% vs 7%, p=0.015) in patients with IR compared to responders. Additionally, patients with IR exhibited a lower % change in CTX following therapy in comparison to responders (median -37% [IQR -68; -16%] vs -57% [-74; -32], p=0.029, respectively), and higher serum CTX levels after treatment (median 236pg/mL [IQR 162; 344] vs 165pg/mL [119; 254], p=0.004). The likelihood of IR was greater with oral bisphosphonates then with ZA (OR 2.61, IC95% 1.16–5.81, p=0.002), and with anticonvulsants use (OR 2.94. IC95% 1.19–7.25, p=0.019). The association with IR persisted for both variables (p≤0.01), when accounted simultaneously in the same model, along with age and gender. Conclusion: Inadequate bisphosphonate response was present in 15% of individuals, which was independently associated with anticonvulsant use and particularly among those on oral bisphosphonate therapy rather than ZA. This knowledge may help to clinically identify potential modifiable factors related to unresponsiveness and to optimize treatment accordingly.

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Anxiety Levels Predict Bone Mineral Density in Postmenopausal Women Undergoing Oral Bisphosphonates: A Two-Year Follow-Up

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18158144 ◽

2021 ◽

Vol 18 (15) ◽

pp. 8144

Author(s):

Gabriella Martino ◽

Federica Bellone ◽

Carmelo M. Vicario ◽

Agostino Gaudio ◽

Andrea Caputo ◽

...

Keyword(s):

Bone Mineral Density ◽

Bone Mineral ◽

Rating Scale ◽

Osteoporotic Fractures ◽

Oral Bisphosphonates ◽

Mineral Density ◽

X Ray ◽

Hamilton Anxiety Rating Scale ◽

Anxiety Levels

Clinical psychological factors may predict medical diseases. Anxiety level has been associated with osteoporosis, but its role on bone mineral density (BMD) change is still unknown. This study aimed to investigate the association between anxiety levels and both adherence and treatment response to oral bisphosphonates (BPs) in postmenopausal osteoporosis. BMD and anxiety levels were evaluated trough dual-energy X-ray absorptiometry and the Hamilton Anxiety Rating Scale (HAM-A), respectively. Participants received weekly medication with alendronate or risedronate and were grouped according to the HAM-A scores into tertiles (HAM-A 3 > HAM-A 2 > HAM-A 1). After 24 months, BMD changes were different among the HAM-A tertiles. The median lumbar BMD change was significantly greater in both the HAM-A 2 and HAM-A 3 in comparison with the HAM-A 1. The same trend was observed for femoral BMD change. Adherence to BPs was >75% in 68% of patients in the HAM-A 1, 79% of patients in the HAM-A 2, and 89% of patients in the HAM-A 3 (p = 0.0014). After correcting for age, body mass index, depressive symptoms, and the 10-yr. probability of osteoporotic fractures, anxiety levels independently predicted lumbar BMD change (β = 0.3417, SE 0.145, p = 0.02). In conclusion, women with higher anxiety levels reported greater BMD improvement, highlighting that anxiety was associated with adherence and response to osteoporosis medical treatment, although further research on this topic is needed.

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AB0330 HIGH REMISSION RATES IN RA – REAL LIFE DATA FROM BARITICINIB

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.5263 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1463.2-1464

Author(s):

S. Bayat ◽

K. Tascilar ◽

V. Kaufmann ◽

A. Kleyer ◽

D. Simon ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Cox Regression ◽

Real Life ◽

Inadequate Response ◽

Research Support ◽

Das 28 ◽

Patient Reported ◽

One Year

Background:Recent developments of targeted treatments such as targeted synthetic DMARDs (tsDMARDs) increase the chances of a sustained low disease activity (LDA) or remission state for patients suffering rheumatoid arthritis (RA). tsDMARDs such as baricitinib, an oral inhibitor of the Janus Kinases (JAK1/JAK2) was recently approved for the treatment of RA with an inadequate response to conventional (cDMARD) and biological (bDMARD) therapy. (1, 2).Objectives:Aim of this study is to analyze the effect of baricitinb on disease activity (DAS28, LDA) in patients with RA in real life, to analyze drug persistance and associate these effects with various baseline characteristics.Methods:All RA patients were seen in our outpatient clinic. If a patient was switched to a baricitinib due to medical reasons, these patients were included in our prospective, observational study which started in April 2017. Clinical scores (SJC/TJC 76/78), composite scores (DAS28), PROs (HAQ-DI; RAID; FACIT), safety parameters (not reported in this abstract) as well as laboratory biomarkers were collected at each visit every three months. Linear mixed effects models for repeated measurements were used to analyze the time course of disease activity, patient reported outcomes and laboratory results. We estimated the probabilities of continued baricitinib treatment and the probabilities of LDA and remission by DAS-28 as well as Boolean remission up to one year using survival analysis and explored their association with disease characteristics using multivariable Cox regression. All patients gave informed consent. The study is approved by the local ethics.Results:95 patients were included and 85 analyzed with available follow-up data until November 2019. Demographics are shown in table 1. Mean follow-up duration after starting baricitinib was 49.3 (28.9) weeks. 51 patients (60%) were on monotherapy. Baricitinib survival (95%CI) was 82% (73% to 91%) at one year. Cumulative number (%probability, 95%CI) of patients that attained DAS-28 LDA at least once up to one year was 67 (92%, 80% to 97%) and the number of patients attaining DAS-28 and Boolean remission were 31 (50%, 34% to 61%) and 12(20%, 9% to 30%) respectively. Median time to DAS-28 LDA was 16 weeks (Figure 1). Cox regression analyses did not show any sufficiently precise association of remission or LDA with age, gender, seropositivity, disease duration, concomitant DMARD use and number of previous bDMARDs. Increasing number of previous bDMARDs was associated with poor baricitinib survival (HR=1.5, 95%CI 1.1 to 2.2) while this association was not robust to adjustment for baseline disease activity. Favorable changes were observed in tender and swollen joint counts, pain-VAS, patient and physician disease assessment scores, RAID, FACIT and the acute phase response.Conclusion:In this prospective observational study, we observed high rates of LDA and DAS-28 remission and significant improvements in disease activity and patient reported outcome measurements over time.References:[1]Keystone EC, Taylor PC, Drescher E, Schlichting DE, Beattie SD, Berclaz PY, et al. Safety and efficacy of baricitinib at 24 weeks in patients with rheumatoid arthritis who have had an inadequate response to methotrexate. Annals of the rheumatic diseases. 2015 Feb;74(2):333-40.[2]Genovese MC, Kremer J, Zamani O, Ludivico C, Krogulec M, Xie L, et al. Baricitinib in Patients with Refractory Rheumatoid Arthritis. The New England journal of medicine. 2016 Mar 31;374(13):1243-52.Figure 1.Cumulative probability of low disease activity or remission under treatment with baricitinib.Disclosure of Interests:Sara Bayat Speakers bureau: Novartis, Koray Tascilar: None declared, Veronica Kaufmann: None declared, Arnd Kleyer Consultant of: Lilly, Gilead, Novartis,Abbvie, Speakers bureau: Novartis, Lilly, David Simon Grant/research support from: Else Kröner-Memorial Scholarship, Novartis, Consultant of: Novartis, Lilly, Johannes Knitza Grant/research support from: Research Grant: Novartis, Fabian Hartmann: None declared, Susanne Adam: None declared, Axel Hueber Grant/research support from: Novartis, Lilly, Pfizer, EIT Health, EU-IMI, DFG, Universität Erlangen (EFI), Consultant of: Abbvie, BMS, Celgene, Gilead, GSK, Lilly, Novartis, Speakers bureau: GSK, Lilly, Novartis, Georg Schett Speakers bureau: AbbVie, BMS, Celgene, Janssen, Eli Lilly, Novartis, Roche and UCB

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ISMAR-study presentation: in-hospital epidemiology and clinical management of respiratory and cardiac comorbidities in cardiac and respiratory disease units

Multidisciplinary Respiratory Medicine ◽

10.4081/mrm.2014.406 ◽

2014 ◽

Vol 9 ◽

Author(s):

Roberto Tramarin ◽

Mario Polverino ◽

Maurizio Volterrani ◽

Bruna Girardi ◽

Claudio Chimini ◽

...

Keyword(s):

Clinical Practice ◽

Clinical Management ◽

Real Life ◽

Length Of Hospital Stay ◽

Relevant Information ◽

Hospital Epidemiology ◽

Discharge Data ◽

Definition Of ◽

Current Guidelines

Background: Cardiovascular and respiratory diseases are leading causes of morbidity and their co-occurrence has important implications in mortality and other outcomes. Even the most recent guidelines do not reliably address clinical, prognostic, and therapeutic concerns due to the overlap of respiratory and cardiac diseases. Study objectives and design: In order to evaluate in the reality of clinical practice the epidemiology and the reciprocal impact of cardio-pulmonary comorbidity on the clinical management, diagnostic workup and treatment, 1,500 cardiac and 1,500 respiratory inpatients, admitted in acute and rehabilitation units, will be enrolled in a multicenter, nationwide, prospective observational study. For this purpose, each center will enroll at least 50 consecutive patients. At discharge, data analysis will be aimed at the definition of cardiac and pulmonary inpatient comorbidity prevalence, demographic characteristics, length of hospital stay, and risk factors, taking into account also procedures, pharmacological and non-pharmacological treatment, and follow up in patients with cardio-respiratory comorbidity. Conclusions: The purely observational design of the study aims to give new relevant information on the assessment and management of overlapping patients in real life clinical practice, and new insight for improvement and implementation of current guidelines on the management of individual diseases.

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P378 Mucosal healing is achieved in most of the inflammatory bowel disease patients in clinical remission with vedolizumab: a real-life single-centre experience

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.507 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S355-S355

Author(s):

M I Calvo Moya ◽

I Omella Usieto ◽

M I Vera Mendoza ◽

V Matallana Royo ◽

I Gonzalez Partida ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Clinical Practice ◽

Bowel Disease ◽

Clinical Remission ◽

Real Life ◽

Mucosal Healing ◽

Surveillance Colonoscopy ◽

Previously Treated ◽

Inflammatory Bowel

Abstract Background Current therapeutic goals in inflammatory bowel disease (IBD) include not only the mere absence of symptoms but also the resolution of endoscopic lesions, so-called mucosal healing (MH), which has been related to better outcomes. Data regarding the achievement of MH with vedolizumab (VDZ) in real-life clinical practice is still scarce. Methods Retrospective cohort study was carried out in a tertiary hospital between January 2015 and April 2019 including patients with a basal colonoscopy showing activity and who achieved clinical remission under treatment with VDZ, defined by partial Mayo score <2 for ulcerative colitis (UC) and Harvey–Bradshaw Index score (HBI) <4 for Crohn’s disease (CD). Surveillance colonoscopy was performed along with the follow-up according to clinical practice. In UC patients, MH was defined as Mayo Endoscopic Subscore (MES) = 0; the endoscopic response was defined by a decrease in MES ≥1 point. In CD, MH was deﬁned by achievement SES-CD = 0–3 or Rutgeerts index i0; the endoscopic response was deﬁned by a decrease of SES-CD of 50% or Rutgeerts index <i2 with at least 1 point of decease compared with baseline. Results In total, 118 patients treated with VDZ were analysed, but only 45 met inclusion criteria with a median follow-up of 21 (IQR: 14–19) months. Surveillance colonoscopy was performed after a median time of 12 months (IQR:9–17) of treatment. MH achieved in 33/45 patients (73%): 17/23 CD patients (74%) and 16/22 UC patients (73%). The endoscopic response was achieved in 9 of the remaining 12 patients: 3/6 CD patients and 6/6 UC patients. Only 3 (7%) of patients included showed no endoscopic benefit at the time of surveillance endoscopy. In multivariate analysis, probability of not achieving MH was 75% in patients previously treated with immunosuppressants (ISS) (HR 0.25, 0.11–0.55 IC95; p = 0.001) and 60% in patients previously treated with anti-TNFα (HR 0.40, 0.18–0.90 95% CI; p = 0.026). Type of IBD, concomitant ISS, corticosteroid use at induction, baseline endoscopy score or duration of disease before VDZ treatment were not associated with the achievement of MH. Conclusion In our experience, most of the patients who achieve clinical remission with VDZ also achieve MH. Refractory patients were less likely to achieve MH despite having achieved clinical remission.

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O35 Efficacy & safety of tocilizumab in GCA: a multi-centre experience of NHS clinical practice

Rheumatology ◽

10.1093/rheumatology/keaa110.034 ◽

2020 ◽

Vol 59 (Supplement_2) ◽

Author(s):

Alwin Sebastian ◽

Abdul Kayani ◽

Chavini Ranasinghe ◽

Frances Hall ◽

Colin Ransom ◽

...

Keyword(s):

Clinical Practice ◽

Life Experience ◽

Real Life ◽

Aneurysm Rupture ◽

Research Support ◽

Ischemic Disease ◽

Abdominal Aortic ◽

Relapsing Remitting ◽

Sight Loss

Abstract Background Giant cell arteritis (GCA) has a relapsing, remitting course with ischemic/vascular damage in a number of cases. Glucocorticoids (GC) remain mainstay of treatment with SAEs e.g. diabetes and fractures commonly seen. The GiACTA trial of tocilizumab (TCZ) in GCA led to NICE approval for 12 month’s therapy in relapsing/ refractory disease. We report real life experience in 51 cases. Methods Multicentre retrospective data collected through ENRAD and individual centres across England (Table 1). Outcomes were as assessed by supervising clinicians. Results Fifty-one patients were treated with TCZ (26 cranial, 13 LVV, 11 both). 11 (22.0%) had prior permanent sight loss due to AION, CRAO or both. One died prior to TCZ, from recurrent cerebral infarcts. Mean age was 71 years with 66.7% females. Ultrasound (US) was used for diagnosis in 28 (56.0%), exclusively or in combination with other tests such as biopsy, PET-CT or CTA. 70% had prior DMARD (LEF/MTX/AZT/MMF/CYC, mean duration 58 weeks). MTX was used in 50% alone or combination. Initial TCZ was given as subcutaneous or intravenous (85.4% and 14.6%). TCZ indication in 89.8% was relapsing, refractory or ischemic disease. Steroid AEs that prevented optimal GC dosing constituted 10% of TCZ indication. Mean follow up was 31 weeks, 30 (58.8%) continuing TCZ uninterrupted, 4 completed 12 months, 4 discontinued due to SAEs. Ten had brief interruptions due to minor AEs. One restarted after 12 months due to flare but died 12 weeks later from abdominal aortic aneurysm rupture. At follow up, 37(74%) were in remission with a mean GC dose of 6.97 mg (mean GC dose pre-TCZ 33.2 mg), Thirty-two (65.3%) ≤ 5mg. In 4 (8%) outcome could not be assessed as either they started TCZ recently or about to start. In 53% lipids were not checked after commencing TCZ. AEs seen were 37.0%. Conclusion In clinical practice, TCZ is efficacious and safe in relapsing/refractory/ischemic GCA. I.V. route is an option awaiting NHSE approval in refractory visual symptoms. Infections and other AEs do occur but overall safety profile is acceptable. US is excellent in identifying patients at need and is a useful disease activity monitoring tool. Disclosures A. Sebastian: None. A. Kayani: None. C. Ranasinghe: None. F. Hall: Consultancies; Sobi, S. Grants/research support; Actelion. C. Ransom: None. D. Jayne: None. V. Quick: Honoraria; Roche. M. Hughes: None. J. Stack: Member of speakers’ bureau; Roche. C. Mukhtyar: None. F. Coath: None. A. Bharadwaj: None. V. Hajela: None. S. Butler: Consultancies; Lily. M. Lwin: None. C. Edwards: Consultancies; Roche, Chugai. Grants/research support; Roche, Chugai. M. Whitlock: None. B. Dasgupta: Consultancies; Roche, Sanofi, GSK. Grants/research support; Roche.

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P663 Efficacy of tofacitinib in patients with ulcerative colitis after previous ineffective biological therapies

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.791 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S545-S546

Author(s):

M Rutka ◽

K Farkas ◽

D Pigniczki ◽

K Szántó ◽

B Anita ◽

...

Keyword(s):

Ulcerative Colitis ◽

Clinical Response ◽

Induction Therapy ◽

Dose Escalation ◽

Real Life ◽

Janus Kinase ◽

Inadequate Response ◽

Mayo Score ◽

Number Of Patients

Abstract Background Tofacitinib (TFC) is an oral, small-molecule Janus kinase inhibitor, which was recently approved for moderate to severe ulcerative colitis (UC). The aim of the current real-life study was to determine efficacy of TFC induction therapy regarding the clinical response and remission in patients with active UC. We evaluated short-term efficacy data in a Hungarian cohort with prior exposure to other biological agents such as anti-TNF drugs and vedolizumab. Methods In this single-centre retrospective study, patients with TFC introduction were included. Since January 2019, a total of 16 patients received an oral TFC induction therapy in a dose of 10 mg twice daily for 8 weeks. Endoscopic activity was evaluated by endoscopic Mayo (eMayo) score before the introduction of TFC and in case of an inadequate therapeutic response to the 5-mg-therapy to confirm therapeutic decision-making. Based on the evaluation of clinical symptoms and laboratory parameters, we either kept the dosage or reduced the dose to 5 mg according to local regulations. We also collected data from the 16. and 24. weeks of the therapy. Primary endpoints were a clinical response (as a reduction in partial Mayo Score [pMayo] by minimum 3 points) or remission (as a Mayo score of the maximum of 2 points and without blood in stool) at week 8. Results Sixteen patients had received the induction therapy (mean age: 36 years, 7 males and 9 females) in our centre. After 8 weeks, 12 (75%) patients responded to the TFC induction therapy and 6 (37.5%) of them were in remission. Four patients were primary non-responders (25%). Corticosteroid therapy (18 ± 7 mg) was required during the induction in 4 responder cases, which could be stepped down by week 8. As a continuous maintenance therapy, 4 patients have already reached the 16th week and 8 have completed the 24th week. By the end of the follow-up, 12 patients responded and 10 was in remission. During the observation period, 3 patients had to remain on 10 mg TFC dose, 6 patients required dose escalation from 5 mg to 10 mg and 5 mg was sufficient in case of only 3 patients after the introduction. Endoscopic activity showed a moderate decrease from 2.5 ± 0.5 eMayo score to 2 ± 1 (n = 7) until week 16. In respect the responder patients, CRP levels decreased from the mean of 7.23 to 5.02. No serious side-effects were observed during the follow-up. Conclusion After the 8-week TFC induction therapy, the response rate was high and only every fourth patients were non-responder. A low number of patients had adequate reactions to the 5 mg-therapy after the introduction, but TFC is effective with dose-escalation in respect of clinical response and remission in patients with UC, who have had an inadequate response to previous biological therapy.

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Factors associated with bone mineral density loss in patients with spondyloarthropathies: A 4-year follow-up study

Medicina ◽

10.1016/j.medici.2015.08.001 ◽

2015 ◽

Vol 51 (5) ◽

pp. 272-279 ◽

Cited By ~ 3

Author(s):

Lina Vencevičienė ◽

Irena Butrimienė ◽

Rimantas Vencevičius ◽

Eglė Sadauskienė ◽

Vytautas Kasiulevičius ◽

...

Keyword(s):

Bone Mineral Density ◽

Bone Mineral ◽

Mineral Density ◽

Bone Mineral Density Loss ◽

Factors Associated ◽

Follow Up Study

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Usage and factors associated with adjuvant bisphosphonate therapy among postmenopausal women diagnosed with early-stage breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e12532 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e12532-e12532

Author(s):

Veera Durga Sravanthi Panuganty ◽

Suganija Lakkunarajah ◽

Sumugan Shanmuganathan ◽

Morgan Black ◽

Sharifa Nasreen ◽

...

Keyword(s):

Breast Cancer ◽

Clinical Practice ◽

Adjuvant Chemotherapy ◽

Postmenopausal Women ◽

Early Breast Cancer ◽

Breast Cancer Mortality ◽

Bisphosphonate Therapy ◽

Collaborative Group ◽

Time Interval ◽

Factors Associated

e12532 Background: Early Breast Cancer Trialist Collaborative Group meta-analysis suggested significant reduction in bone metastasis and breast cancer mortality among post-menopausal women diagnosed with early breast cancer when treated with an adjuvant bisphosphonate. Cancer Care Ontario and American Society of Clinical Oncology clinical practice guideline published in 2017, recommends the use of an adjuvant bisphosphonate in postmenopausal women who are candidates for adjuvant systemic therapy. Our goal was to evaluate trends and factors associated with adjuvant bisphosphonate usage since the guideline’s publication. Methods: This study is a retrospective review of postmenopausal women treated for early breast at the London Regional Cancer Program from 2017-2018. Univariate and a multivariable logistic regression models were used to investigate factors potentially associated with adjuvant bisphosphonate use including age, stage, grade, estrogen receptor, progesterone receptor, HER2 receptor status and previous use of adjuvant chemotherapy. The percentage of patients offered, receiving and declining therapy was also recorded and the time interval from surgery to start of bisphosphonate therapy (< 6 months, 6-12 months or >12 months). Results: We identified 286 postmenopausal breast cancer patients, of whom 75 (28%) received adjuvant bisphosphonate therapy. In our multivariable model, cancer stage [odds ratio (OR) stage II vs. I=2.26, 95% confidence interval (CI) 1.08-4.74) and OR Stage III vs. I=4.94, 95% CI 1.84-13.17] and previous use of adjuvant chemotherapy (OR=2.76, 95%CI 1.37-5.55) were significantly associated with adjuvant bisphosphonate use. Among 133 patients who received adjuvant systemic chemotherapy, 51% were offered adjuvant bisphosphonate and of these 81% patients accepted therapy. Among a total of 75 patients receiving adjuvant bisphosphonate therapy 19% initiated therapy within 6 months of surgery, 48% within 6-12 months of surgery, and 33% after 12 months following surgery. Conclusions: Stage and previous use of chemotherapy were significantly associated with adjuvant bisphosphonate therapy. Our study observes the potential underutilization of adjuvant bisphosphonate therapy and possible need to start treatment earlier in some patients. Further education and awareness of the clinical practice guidelines regarding adjuvant bisphosphonate therapy may be warranted and additional population-based study investigating treatment patterns and real-world effectiveness.

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