Efficacy of calcitonin for treating acute pain associated with osteoporotic vertebral compression fracture: an updated systematic review

ABSTRACTObjectiveAcutely painful osteoporotic vertebral compression fractures are associated with hospitalization and mortality in older adults. Calcitonin may be an alternative to opioid or nonopioid analgesia for treating acute compression fracture pain in emergency and primary care settings. This review summarizes pain, function, and adverse events associated with calcitonin.MethodsWe searched MEDLINE, EMBASE, The Cochrane Library, clinical trials registries, and reference lists of included studies. Eligible studies evaluated the effect of synthetic calcitonins (salmon, eel, and human) on pain scores in adults ≥60 years old with a recent atraumatic compression fracture. Two reviewers screened studies, extracted data, and allocated bias in duplicate. A random effects meta-analysis evaluated standard mean difference (SMD) and heterogeneity (I2).ResultsOf 1,198 articles screened, 11 were included (9 in the meta-analysis). Treatment lasted from 14 days to 6 months. Pain was lower in the salmon calcitonin group (100–200 IU IM or NAS, daily) than the control group with high certainty of evidence at week 1 (SMD, -1.54; 95% confidence interval [CI], -2.02 – -1.06; I2 = 52%), representing a number needed to treat of two. The analgesic efficacy of salmon calcitonin at 4 weeks was unclear due to substantial heterogeneity. There was low certainty evidence that calcitonin did not increase the overall risk of adverse events, including nausea and vomiting (risk ratio, 2.10; 95% CI, 0.87–5.08; I2 = 47%).ConclusionsCalcitonin is beneficial and appears safe for treating acute pain associated with compression fractures. Further studies may improve the certainty of evidence.

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LO12: Efficacy of calcitonin for treating acute pain associated with osteoporotic vertebral compression fracture: an updated systematic review and meta-analysis

CJEM ◽

10.1017/cem.2019.55 ◽

2019 ◽

Vol 21 (S1) ◽

pp. S11

Author(s):

E. Boucher ◽

B. Rosgen ◽

E. Lang

Keyword(s):

Adverse Events ◽

Nasal Spray ◽

Acute Pain ◽

Meta Analysis ◽

Compression Fracture ◽

Sensitivity Analyses ◽

Current Evidence ◽

Vertebral Compression Fractures ◽

Control Group ◽

Standard Mean Difference

Introduction: Acutely painful osteoporotic vertebral compression fractures (OVCFs) are common in elderly individuals. Most OVCFs result from falls or routine activities, such as lifting objects or bending. OVCFs are associated with increased hospitalization, mortality and reduced quality of life. Calcitonin has been studied as an alternative or adjunct to opioid or non-opioid analgesia for treating acute pain associated with OVCFs. This review evaluates current evidence on the benefits and harms of calcitonin related to OVCFs. Methods: We registered our review protocol on PROSPERO (CRD42018084850) and conducted our study in compliance with PRISMA guidelines. We searched MEDLINE, EMBASE, The Cochrane Database of Systematic Reviews, clinical trials registries, conference papers and reference lists of included studies. Eligible studies evaluated the effect of calcitonin on pain scores in adults ≥60 years-old with a recent OVCF ( <45 days prior). Two reviewers independently screened studies, extracted data and allocated bias in duplicate. Data were pooled for meta-analysis using standard mean difference (SMD) and a random-effects model. Heterogeneity was evaluated with I2 and sensitivity analyses were performed. The certainty of evidence was assessed with GRADE criteria. Our primary outcome was pain; secondary outcomes include mobility and adverse events. Results: 1180 articles were screened, 11 eligible studies were identified and 9 (627 participants) were pooled for meta-analysis. Pain at rest was lower in the calcitonin group than the control group at week 1 (SMD -1.11, 95% confidence interval (CI) -1.95 to -0.26, I2 = 92%). Sensitivity analysis showed that the route of administration influenced this effect: the SMD for calcitonin nasal spray was -1.88 (95% CI -2.31 to -1.44, I2 = 53%) compared to -0.35 (95% CI -0.86 to 0.17, I2 = 60%) for intramuscular injection. Improvements in mobility were observed at week 4 (SMD -0.48, 95% CI -0.79 to -0.17, I2 = 45%). The risk of adverse events was increased with calcitonin (Risk Ratio 2.72, 95% CI 0.90 to 8.17, I2 = 41%) and consisted of flushing, headache, dizziness and gastrointestinal effects. The overall certainty of evidence was downgraded to low due to concerns over risk of bias and inconsistency between studies. Conclusion: Calcitonin, particularly as a nasal spray, is beneficial and safe for treating acute pain associated with OVCFs. Further studies are needed to improve the certainty of evidence.

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Nervous and Muscular Adverse Events after COVID-19 Vaccination: A Systematic Review and Meta-Analysis of Clinical Trials

Vaccines ◽

10.3390/vaccines9080939 ◽

2021 ◽

Vol 9 (8) ◽

pp. 939

Author(s):

Jiaxin Chen ◽

Yuangui Cai ◽

Yicong Chen ◽

Anthony P. Williams ◽

Yifang Gao ◽

...

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Adverse Events ◽

Fixed Effects ◽

Meta Analysis ◽

Phase 1 ◽

Cochrane Library ◽

Categorical Variables ◽

Control Group ◽

Open Label

Background: Nervous and muscular adverse events (NMAEs) have garnered considerable attention after the vaccination against coronavirus disease (COVID-19). However, the incidences of NMAEs remain unclear. We aimed to calculate the pooled event rate of NMAEs after COVID-19 vaccination. Methods: A systematic review and meta-analysis of clinical trials on the incidences of NMAEs after COVID-19 vaccination was conducted. The PubMed, Medline, Embase, Cochrane Library, and Chinese National Knowledge Infrastructure databases were searched from inception to 2 June 2021. Two independent reviewers selected the study and extracted the data. Categorical variables were analyzed using Pearson’s chi-square test. The pooled odds ratio (OR) with the corresponding 95% confidence intervals (CIs) were estimated and generated with random or fixed effects models. The protocol of the present study was registered on PROSPERO (CRD42021240450). Results: In 15 phase 1/2 trials, NMAEs occurred in 29.2% vs. 21.6% (p < 0.001) vaccinated participants and controls. Headache and myalgia accounted for 98.2% and 97.7%, and their incidences were 16.4% vs. 13.9% (OR = 1.97, 95% CI = 1.28–3.06, p = 0.002) and 16.0% vs. 7.9% (OR = 3.31, 95% CI = 2.05–5.35, p < 0.001) in the vaccine and control groups, respectively. Headache and myalgia were more frequent in the newly licensed vaccines (OR = 1.97, 95% CI = 1.28–3.06, p = 0.02 and OR = 3.31, 95% CI = 2.05–5.35, p < 0.001) and younger adults (OR = 1.40, 95% CI = 1.12–1.75, p = 0.003 and OR = 1.54, 95% CI = 1.20–1.96, p < 0.001). In four open-label trials, the incidences of headache, myalgia, and unsolicited NMAEs were 38.7%, 27.4%, and 1.5%. Following vaccination in phase 3 trials, headache and myalgia were still common with a rate of 29.5% and 19.2%, although the unsolicited NMAEs with incidence rates of ≤ 0.7% were not different from the control group in each study. Conclusions: Following the vaccination, NMAEs are common of which headache and myalgia comprised a considerable measure, although life-threatening unsolicited events are rare. NMAEs should be continuously monitored during the ongoing global COVID-19 vaccination program.

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Decreased Mortality in Coronavirus Disease 2019 Patients Treated With Tocilizumab: A Rapid Systematic Review and Meta-analysis of Observational Studies

Clinical Infectious Diseases ◽

10.1093/cid/ciaa1445 ◽

2020 ◽

Cited By ~ 12

Author(s):

Jishnu Malgie ◽

Jan W Schoones ◽

Bart G Pijls

Keyword(s):

Side Effects ◽

Meta Analysis ◽

Risk Difference ◽

World Health ◽

Cochrane Library ◽

Control Group ◽

Number Needed To Treat ◽

Receptor Antagonists ◽

Increased Risk ◽

Health Organization

Abstract Background We systematically reviewed the literature to answer the following research questions: (1) Does interleukin 6 (IL-6) (receptor) antagonist therapy reduce mortality in coronavirus disease 2019 (COVID-19) patients compared to patients not treated with IL-6 (receptor) antagonists; and (2) is there an increased risk of side effects in COVID-19 patients treated with IL-6 (receptor) antagonists compared to patients not treated with IL-6 (receptor) antagonists? Methods We systematically searched PubMed, PMC PubMed Central, Medline, World Health Organization COVID-19 Database, Embase, Web of Science, Cochrane Library, Emcare, and Academic Search Premier (through 30 June 2020). Random effects meta-analysis was used to pool the risk ratios and risk differences of individual studies. Risk of bias was appraised using the Methodological Index for Non-randomized Studies (MINORS) checklist. Results The search strategy retrieved 743 unique titles, of which 10 studies (all on tocilizumab [TCZ]) comprising 1358 patients were included. Nine of 10 studies were considered to be of high quality. Meta-analysis showed that the TCZ group had lower mortality than the control group. The risk ratio was 0.27 (95% confidence interval [CI], .12–.59) and the risk difference was 12% (95% CI, 4.6%–20%) in favor of the TCZ group. With only a few studies available, there were no differences observed regarding side effects. Conclusions Our results showed that mortality was 12% lower for COVID-19 patients treated with TCZ compared with those not treated with TCZ. The number needed to treat was 11, suggesting that for every 11 (severe) COVID-19 patients treated with TCZ, 1 death is prevented. These results require confirmation by randomized controlled trials.

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A Systematic Review and Meta-Analysis of Thalidomide in Patients with Previously Untreated Multiple Myeloma.

Blood ◽

10.1182/blood.v108.11.3570.3570 ◽

2006 ◽

Vol 108 (11) ◽

pp. 3570-3570 ◽

Cited By ~ 1

Author(s):

Lisa Hicks ◽

Adam Haynes ◽

Donna E. Reece ◽

Irwin Walker ◽

Jordan A. Herst ◽

...

Keyword(s):

Multiple Myeloma ◽

Relative Risk ◽

Peripheral Neuropathy ◽

Adverse Events ◽

Response Rate ◽

Meta Analysis ◽

Cochrane Library ◽

Number Needed To Treat ◽

Vte Prophylaxis ◽

American Society

Abstract Background: Multiple myeloma disproportionately affects the elderly and is currently an incurable malignancy. New therapies for myeloma, particularly oral therapies, are urgently needed. Objectives: To determine if thalidomide with or without other agents, improves response rate (≥ 50% reduction in monoclonal protein), survival, and/or progression in patients with previously untreated myeloma. To determine the frequency and significance of major adverse events associated with thalidomide in this setting. Methods: A literature search of Medline (1966–June 2006), Embase (1980–June 2006), the Cochrane Library, abstracts from the annual meetings of the American Society of Hematology (1999–2005) and the American Society of Oncology (1999–2006) was completed with a pre-specified search strategy. No language restrictions were applied. Randomized controlled trials of induction thalidomide (any dose, any duration) for adults with previously untreated multiple myeloma were included. Trials of exclusively maintenance therapy were excluded. Two reviewers independently extracted data. The methodological quality of selected trials was assessed and summarized. Weighted data was expressed as relative risk, risk difference, number needed to treat (NNT), and number needed to harm (NNH). A random-effects model was used. Results: Six eligible studies involving almost two thousand patients (N=1875) were identified and meta-analyzed. Two studies were published and four were reported in abstract form only. Five studies reported overall response rate (ORR); the four largest trials reported statistically significant improvements in ORR with the addition of thalidomide to standard therapy. The weighted relative risk of responding to a thalidomide-containing regimen versus control was 1.50 (95% CI 1.21 to 1.86). The NNT to achieve one additional response with thalidomide was 4 (95% CI 2.9 to 8.3). Two trials reported improvements in EFS/PFS. One trial reported an improvement in OS. The risk of VTE, peripheral neuropathy, and constipation was consistently elevated with thalidomide such that for every 50 patients treated with a thalidomide-containing-regimen, one could expect 12 to 13 additional patients to respond, 4 additional patients to develop VTE (NNH 12.5; 95% CI 8.3 to 20), 2 additional patients to develop peripheral neuropathy (NNH 25; 95% CI 16.7 to 50), and 4 additional patients to develop constipation (NNH14; 95% CI 10 to 25). In our analyses, prophylactic anticoagulation appeared to decrease, but not abolish, the risk of VTE with thalidomide. Conclusions: Thalidomide improves response rate and possibly progression free and overall survival in patients with previously untreated myeloma. It also increases the incidence of VTE, neuropathy, constipation and other adverse events. Further studies are required to confirm the survival advantage seen in one study, and to determine the optimum strategy for VTE prophylaxis.

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Repurposing of drugs for Covid-19: a systematic review and meta-analysis

10.1101/2020.06.07.20124677 ◽

2020 ◽

Cited By ~ 1

Author(s):

Pinky Kotecha ◽

Alexander Light ◽

Enrico Checcucci ◽

Daniele Amparore ◽

Cristian Fiori ◽

...

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Adverse Events ◽

Clinical Improvement ◽

Case Reports ◽

Meta Analysis ◽

Case Series ◽

Cochrane Library ◽

Control Group ◽

Significant Difference

AbstractObjectiveThe aim of this systematic review is to evaluate the data currently available regarding the repurposing of different drugs for Covid-19 treatment. Participants with suspected or diagnosed Covid-19 will be included. The interventions being considered are drugs being repurposed, and comparators will include standard of care treatment or placebo.MethodsWe searched Ovid-MEDLINE, EMBASE, Cochrane library, clinical trial registration site in the UK(NIHR), Europe (clinicaltrialsregister.eu), US (ClinicalTrials.gov) and internationally (isrctn.com), and reviewed the reference lists of articles for eligible articles published up to April 22, 2020. All studies in English that evaluated the efficacy of the listed drugs were included. Cochrane RoB 2.0 and ROBINS-I tool were used to assess study quality. This systematic review adheres to the PRISMA guidelines. The protocol is available at PROSPERO (CRD42020180915).ResultsFrom 708 identified studies or clinical trials, 16 studies and 16 case reports met our eligibility criteria. Of these, 6 were randomized controlled trials (763 patients), 7 cohort studies (321 patients) and 3 case series (191 patients). Chloroquine (CQ) had a 100% discharge rate compared to 50% with lopinavir-ritonavir at day 14, however a trial has recommended against a high dosage due to cardiotoxic events. Hydroxychloroquine (HCQ) has shown no significant improvement in negative seroconversion rate which is also seen in our meta-analysis (p=0.68). Adverse events with HCQ have a significant difference compared to the control group (p=0.001). Lopinavir-ritonavir has shown no improvement in time to clinical improvement which is seen in our meta-analyses (p=0.1). Remdesivir has shown no significant improvement in time to clinical improvement but this trial had insufficient power.DiscussionDue to the paucity in evidence, it is difficult to establish the efficacy of these drugs in the treatment of Covid-19 as currently there is no significant clinical effectiveness of the repurposed drugs. Further large clinical trials are required to achieve more reliable findings. A risk-benefit analysis is required on an individual basis to weigh out the potential improvement in clinical outcome and viral load reduction compared to the risks of the adverse events. (1-16)

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Clinical Efficacy and Safety of Omalizumab in the Treatment of Allergic Rhinitis: A Systematic Review and Meta-analysis of Randomized Clinical Trials

American Journal of Rhinology and Allergy ◽

10.1177/1945892419884774 ◽

2019 ◽

Vol 34 (2) ◽

pp. 196-208 ◽

Cited By ~ 7

Author(s):

Chenjie Yu ◽

Kaijian Wang ◽

Xinyan Cui ◽

Ling Lu ◽

Jianfei Dong ◽

...

Keyword(s):

Allergic Rhinitis ◽

Adverse Events ◽

Symptom Score ◽

Meta Analysis ◽

Cochrane Library ◽

Control Group ◽

Life Questionnaire ◽

Efficacy And Safety ◽

Significant Difference ◽

Symptom Scores

Background Patients with moderate to severe allergic rhinitis (AR) who are treated according to the current rhinitis management guidelines may be inadequately controlled. These patients are at risk of serious comorbidities, such as asthma and chronic sinusitis. These symptoms, sneezing and an itchy, runny, stuffy nose, may have a negative impact on patients’ daily functioning. Omalizumab is being developed as a new choice for the treatment of AR. We therefore undertook a meta-analysis to assess the efficacy and safety of omalizumab in the treatment of AR. Methods We systematically searched PubMed, Cochrane Library, and MEDLINE databases for randomized controlled studies on the treatment of AR with omalizumab. Our evaluation outcomes were symptom scores, medication efficacy, combined symptom and medication scores, and adverse events. We descriptively summarized and quantitatively synthesized original data to evaluate the efficacy and safety of omalizumab in the treatment of AR by using Stata12.0 software for meta-analyses. Results The results of our meta-analysis showed that there were statistically significant differences between the omalizumab group and the control group in the following aspects: daily nasal symptom score (standardized mean difference [SMD] = –0.443, 95% confidence interval [CI]: –0.538 to –0.347, P < .001); daily ocular symptom score (SMD = –0.385, 95% CI: –0.5 to –0.269, P < .001); daily nasal medication symptom scores (SMD = –0.421, 95% CI: –0.591 to –0.251, P < .001); proportion of days of emergency drug use (risk ratio [RR] = 0.488, 95% CI: 0.307 to 0.788, P < .005); rhinoconjunctivitis-specific quality of life questionnaire (SMD = –0.286, 95% CI: –0.418 to –0.154, P < .001); and overall evaluation (RR = 1.435, 95% CI: 1.303–1.582, P < .001). There was no statistically significant difference in safety indicator: adverse events (RR = 1.026, 95% CI: 0.916–1.150, P = .655). Conclusion Omalizumab is effective and relatively safe in patients with AR; omalizumab used in conjunction with special immunotherapy has shown promising results, especially in reducing adverse events.

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Helicobacter pylori Eradication Therapy for Functional Dyspepsia: A Meta-Analysis by Region and H. pylori Prevalence

Journal of Clinical Medicine ◽

10.3390/jcm8091324 ◽

2019 ◽

Vol 8 (9) ◽

pp. 1324 ◽

Cited By ~ 6

Author(s):

Seung Joo Kang ◽

Boram Park ◽

Cheol Min Shin

Keyword(s):

Helicobacter Pylori ◽

Functional Dyspepsia ◽

Meta Analysis ◽

Eradication Therapy ◽

Cochrane Library ◽

Control Group ◽

Number Needed To Treat ◽

Helicobacter Pylori Eradication ◽

Dyspeptic Symptoms ◽

H Pylori

Background: Previous studies on the effect of Helicobacter pylori eradication on functional dyspepsia (FD) are conflicting. We performed a comprehensive meta-analysis on this issue according to region and prevalence of H. pylori. Methods: Randomized controlled trials (RCTs) evaluating the effect of eradication of H. pylori on functional dyspepsia up to December 2018 were searched through PubMed, EMBASE, and the Cochrane Library. Subgroup analyses by the outcome measure, region, and prevalence of H. pylori were performed. All data were analyzed with Review Manager 5.3. Results: Eighteen RCTs were included in our meta-analysis. Overall, the H. pylori eradication group showed significant improvement of symptoms compared with the control group (risk ratio (RR) = 1.18; 95% confidence interval (CI): 1.07–1.30, p < 0.01). There was moderate heterogeneity among studies (I2 = 34%) and the number needed to treat (NNT) was 15.0. Helicobacter pylori eradication improved dyspeptic symptoms both in low (<50%) and high (≥50%) H. pylori prevalence regions (RR = 1.21 and 1.17; 95% CI: 1.02–1.44 and 1.06–1.29, I2 = 49% and 5%, respectively.) In the analysis of studies from Asia, however, the effect of eradication on improvement of dyspepsia was not significant (RR = 1.14; 95% CI: 0.99–1.33, p = 0.08, I2 = 37%). Conclusion: Overall, H. pylori eradication provides significant improvement of symptoms in functional dyspepsia patients regardless of H. pylori prevalence. However, in the analysis of studies from Asia, the eradication did not significantly improve dyspeptic symptoms. In this region, eradication for dyspepsia can be individualized.

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A Meta-Analysis of the Efficacy of Panax Ginseng on Menopausal Women’s Sexual Function

International Journal of Women s Health and Reproduction Sciences ◽

10.15296/ijwhr.2019.20 ◽

2018 ◽

Vol 7 (1) ◽

pp. 124-133 ◽

Cited By ~ 1

Author(s):

Zahra Ghorbani ◽

Mojgan Mirghafourvand

Keyword(s):

Sexual Dysfunction ◽

Adverse Events ◽

Sexual Function ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Random Effect ◽

Cochrane Library ◽

Control Group ◽

Placebo Control ◽

Significant Difference

Objectives: An increase in life expectancy results in the aging population growth. This study was designed to evaluate the efficacy and adverse events of ginseng that could be used as a herbal medicine in women with sexual dysfunction. Materials and Methods: The authors of this study searched Cochrane Library, MEDLINE, Web of Science, Embase, Scopus, ProQuest, Google Scholar, and Persian databases without a time limitation until May 2018 and examined all the randomized clinical trials (RCTs) that compared the effect of different types of ginseng on sexual function of menopausal women as compared to the placebo controls. The Cochrane risk of bias tool was used to assess the methodological quality of the included studies. The heterogeneity was determined using the I2 index. In addition, standardized mean difference (SMD) was used instead of mean differences (MD) and a random effect was reported instead of fixed effect in meta-analysis. Results: The eligibility criteria were found in five RCTs. All the included studies were placebo-controlled. Two trials had a parallel design while three studies used a crossover design. Although four trials indicated that ginseng significantly improved sexual function, they didn’t report any treatment effect compared to the placebo group. Based on the results of meta-analysis obtained from five studies including 531 women, there was no statistically significant effect of ginseng on female sexual dysfunction (FSD) compared to the placebo control group (SMD: 0.26; 95% CI: -0.26 to 0.76). Nonetheless, there was a considerable heterogeneity among the studies (I2 = 81%; P < 0.0001). Moreover, all the included studies assessed adverse events, but in three of the RCTs, there was no significant difference between the placebo and ginseng groups. Conclusions: The evidence regarding ginseng as a therapeutic agent for sexual dysfunction is unjustifiable. Rigorous studies seem warranted in this respect.

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The safety and efficacy of mesenchymal stem cells in the treatment of COVID-19-associated pneumonia: a systematic review and meta-analysis

10.1101/2021.07.01.21259838 ◽

2021 ◽

Author(s):

Junwu Wang ◽

Pengzhi Shi ◽

Dong Chen ◽

Shuguang Wang ◽

Pingchuan Wang ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Adverse Events ◽

Meta Analysis ◽

Cochrane Library ◽

Control Group ◽

Serious Adverse Events ◽

Safe Method ◽

Radiographic Outcomes ◽

The Difference

Mesenchymal stem cells (MSCs) therapy is considered one of the most promising treatments in the context of the coronavirus disease 2019 (COVID-19) pandemic. However, the safety and effectiveness of MSCs in the treatment of COVID-19-associated pneumonia patients need to be systematically reviewed and analyzed. Two independent researchers searched for the relevant studies published between October 2019 and April 2021 in PubMed, Embase, Cochrane Library, WAN FANG, and CNKI databases. A total of 22 studies involving 371 patients were included in the present study. MSCs were administered in 247 participants, and MSCs were allogeneic from umbilical cord, adipose tissue, menstrual blood, placenta, Wharton's jelly, or unreported sources. Combined results found that MSCs group significantly reduced the incidence of adverse events (OR = 0.43, 95%CI. = 0.22~0.84, P = 0.01) and mortality (OR = 0.17, 95%CI. = 0.06~0.49, P < 0.01), and the difference compared with control group was statistically significant. No MSCs treat-related serious adverse events were reported. The lung function and radiographic outcomes, and biomarker levels of inflammation and immunity all showed improvement trends. Therefore, MSCs therapy is an effective and safe method in the treatment of COVID-19-associated pneumonia and shows advantages in less adverse events and mortality. However, a standard and effective MSCs treatment program needs to be developed.

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Efficacy and Toxicity Profile of Elotuzumab for Multiple Myeloma: A Systematic Review and Meta-Analysis

Blood ◽

10.1182/blood-2018-99-117209 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 5640-5640

Author(s):

Faiza Jamil ◽

Madeeha Shafqat ◽

Sharoon Samuel ◽

Zunairah Shah ◽

Ceren Durer ◽

...

Keyword(s):

Multiple Myeloma ◽

Clinical Trials ◽

Adverse Events ◽

Meta Analysis ◽

Single Agent ◽

Random Effect Model ◽

Drug Regimen ◽

Pooled Analysis ◽

Cochrane Library ◽

Control Group

Abstract Background: Elotuzumab (elo) is a humanized monoclonal antibody, which has been approved by the FDA for use in combination with lenalidomide (lena) and dexamethasone (dexa) in patients (pts) with relapsed and refractory multiple myeloma (RRMM). Elotuzumab is effective as a single agent, as well as in combination for multiple myeloma treatments, supporting the use of elo in pts with RRMM and newly diagnosed multiple myeloma (NDMM) pts. Method: After review of literature using database searches was done on 6/27/18 (Pubmed, Embase, Cochrane Library, Web of Science and Clinical Trials.gov), 9 prospective and 1 retrospective study with 1128 enrolled pts met the inclusion criteria to date in RRMM and 2 clinical trials including 123 pts in NDMM (Table 1). CMA software v.3 was used for meta-analysis. A random-effect model was applied. Result: Regimens used in RRMM: Based on pooled analysis (95% CI), an overall response rate (ORR) of 66% (54-76.2) was calculated in 685 evaluable pts treated with elo based regimens in RRMM (Figure 1). Most common grade (G) ≥ 3 hematological adverse events (HAE) and non-hematological adverse events (NHAE) based on regimen were calculated using pooled analysis in RRMM pts (Table 2). Anemia was noted in 12.1% ( 7.7-18.6) in 559 pts, while neutropenia in 14.5% (7.5-26.4) out of 591 pts and thrombocytopenia (tcp) in 11.9% (7.9-17.4) in 198 evaluable pts. Diarrhea 5.5% (3.6-8.3), pyrexia 2.4% (1.5-4), peripheral neuropathy (PN) 8.4% (3.8-17.8) were measured in 626, 668 and 143 pts respectively. Elotuzumab as monotherapy: 1 study (n=34) evaluated the efficacy of elo as single agent in RRMM. The median age, time from diagnosis and number of prior therapies were 64.5 years (y) (46-87), 4.4 y (0.9-12.8) and 4.5 y (2-10) respectively. It produced an ORR of 1.4% (0.1-19.1 95% CI) in 34 evaluable pts. Adverse events recorded were pyrexia and fatigue in 17.6% and 8.8% pts respectively. Elotuzumab in two drug regimen: In RRMM, 2 clinical trials (n=49) evaluated the efficacy (95% CI) of elo, ORR of 25% (4.1-72.3) was calculated. The best PFS (progression free survival) produced was in combination of elo 20 mg with bortezumib (bort) 1.3mg/m2 of 9.46 months as compared to 1.8 months when elo10mg/kg + dexamethasone (dexa) 28mg was used. In our analysis for safety, common G≥ 3 HAE calculated were, thrombocytopenia 8.7% (3.3-21.1) n=49, neutropenia 10.7 % (3.5-28.4) n=28 pts and anemia 7.1% (1.8-24.5) n=28 pts. NHAE included diarrhea 1.7% (0.1-22.3), PN 10.7% (3.5-28.4), pyrexia 1.7% (0.1-22.3) in 28 evaluable pts each. Elotuzumab in three drug regimen: In RRMM, 10 clinical trials including 602 pts evaluated the efficacy of elo as a part of triple drug regimen, producing an ORR of 72.2% (54-76.2). The best results were produced with the combination of elo 10-20mg/kg + lenalidomide (lena) 25mg + dexa 40mg producing a PFS of 32.2 mo and 28.62 mo in its phase I and II cohorts respectively. Based on pooled analysis (95% CI) common HAE calculated were neutropenia 17.5% (7.6-35.4) in n=563, thrombocytopenia 12.7% (8.2-19.4) in n=149 and anemia 13% (8-20.5) in n=531 pts. Common G ≥ 3 NHAE estimated were diarrhea 5.7% (3.7-8.6), PN 6.6% (2-19.2), pyrexia 2.5% (1.5-4.1) in 598, 115 and 640 pts respectively. Elotuzumab based regimen in NDMM: A currently ongoing clinical trial NCT02272803 has produced promising results in NDMM pts. As a part of three drug regimen with dose of elo 10mg/kg-20mg/kg, lena 25mg, dexa 20mg in 40 pts produced an ORR of 87.5% (73.2-95.8) versus control group of lena 25mg plus dexa 40mg in 42 pts with an ORR of 73.8% (58-86.1). The PFS rate recorded at 1 year was 93% (79-98%) and 91% (73-97%) respectively. The HAE G ≥ 3 included, neutropenia 18% and leukopenia 15%. In another study with 41 pts, elo was used in combination with lena, bort and dexa producing an ORR of 100% and greater than grade 3 adverse events including Tcp 15%, PN 2%. Conclusion: Results produced in our study suggest that elotuzumab is highly effective when used in pts with RRMM and NDMM. Combination regimens for elo produces an ORR ranging from 79-83% with elo + lena+ dexa, proving that the best results were produced by three drug regimens. Large prospective studies are required to evaluate efficacy and safety of elotuzumab in combination therapies. Disclosures No relevant conflicts of interest to declare.

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