Tapering Regimen Research Articles

Reduced Narcotic Utilization in Total Joint Arthroplasty Patients in an Urban Tertiary Care Center.

Opioid use after total joint arthroplasty must be balanced against the risks of opioid dependence and diversion. This study sought to define the baseline patient characteristics and discharge opioid use after the initiation of a preoperative and postoperative institutional opioid prescription protocol in a population with a high prevalence of opioid dependence and substance use. Data on 1004 patients undergoing total joint arthroplasties from July 1, 2017, to June 30, 2019, were retrospectively reviewed. Demographics were collected, and data were grouped into high- and low-discharge opioid groups based on 1 standard deviation above or below the mean. Patient characteristics of the high and low groups were compared using one-way analysis of variance and Pearson chi-square test. The prevalence of preoperative opioid dependence was 21.8%. The mean discharge opioid prescription was 264 morphine milligram equivalents (MMEs). The cutoffs of high- and low-use groups were above 424 MMEs and below 104.5 MMEs. The high-discharge opioid group was more likely to be male, younger, to have a history of preoperative opioid use, to undergo general anesthesia, and to be uninsured. The lower-discharge opioid group was more likely to be older, female, to have Medicare, and to stay approximately 1day longer in the hospital. Body mass index, intraoperative opioid requirement, American Society of Anesthesiologists Classification score, race, total knee vs total hip arthroplasty, or surgical approach for total hip arthroplasty did not affect discharge opioid prescriptions. Reduction of opioid prescriptions at discharge in total joint arthroplasty patients may be possible with the use of preoperative and postoperative protocols, optimizing patient risk factors for opioid use and utilizing a patient-specific opioid taper regimen.

Bilateral uveitis following nivolumab and ipilimumab treatment for mesothelioma

AbstractPurpose: Case report of a patient presenting with sudden onset of painful decreased vision in both eyes, diagnosed with Intermediate uveitis and keratitis. We will review the diagnostic pathway and the management of this case, as well as the correlation with the systemic treatment of that time.Results: A 63‐year‐old male presented in the Emergency department with bilateral red painful eyes and blurred vision. The patient had a past ophthalmic history of keratouveitis in RE and medical history of mesothelioma for which he had recently started treatment with Nivolumab and Ipilimumab. The visual acuity on presentation was 6/9 in the RE and 6/6 in the LE. Upon examination BE were hyperaemic, there was a past corneal scar in the RE and bilateral KPs. RE had +1 AC inflammation and LE traces of AC inflammation. No signs of posterior segment inflammation were seen in both eyes. The patient was treated initially with oral Aciclovir 400 mg BD and Pred Forte 1% in BE QDS. One week after initiation of treatment symptoms improved and a tapering regime of the local steroid treatment was given. Four weeks later the visual acuity in the RE was 6/12 and 6/9 in the LE. Upon examination there was +1 AC activity in BE and +1 vitreous activity. OCT demonstrated bilateral macular oedema. An FFA revealed bilateral optic disc hyperfluorescence. Upon further discussion of the patient's medical history it was revealed that both episodes of intraocular activity coincided with his infusions of Nivolumab and Ipilimumab. The patient was advised to discontinue the oral Aciclovir treatment and was initiated on intensive regime of local steroids which was tapered on improvement of the vision and the inflammation. Our ocular findings were communicated the patient's oncology team that decided to discontinue the above treatment.Conclusions: Nivolumab is an anti‐programmed cell death protein‐monoclonal. It is used for cancer treatment but case reports have emerged of uveitis and ocular surface disease. Ipilimumab is a humanized CLTA‐4 antibody and it can be associated with immune related adverse events such as uveitis. Our patient was switched to a different treatment protocol without further ocular inflammation and excellent visual outcome. Clinicians should raise their index of suspicion in side effects around the timing of treatment.

237 POTENTIALLY INAPPROPRIATE PRESCRIBING IN HOSPITALISED FRAIL OLDER ADULTS: DEVELOPMENT OF THE OPTI-3S PRELIMINARY STATEMENTS

Abstract Background Few assessment criteria exist for Potentially Inappropriate Medications (PIMs) in the hospital setting. This study aims to develop the preliminary statements of OPTI-3S, criteria for optimising medicines by stopping, stepping down or switching to safer alternatives. These are designed to be of value to clinical practitioners in the routine care of hospitalised, frail older adults. Methods A systematic literature review was conducted in the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, PubMed, CINAHL, EMBASE and Scopus (2010-2021). Search terms included the concepts of inappropriate prescribing, deprescribing and the target population (e.g. older, frail, hospitalized). This was supplemented with a PubMed focused search (2010-2021) using key words pertaining to the index diseases/conditions or inappropriate medications. The structured reviews included clinical based guidelines, PIMs lists, systematic/non-systematic reviews, or clinical/observational trials that assessed safe and/or effective use of medications in older adults. The preliminary statements were then drafted based on the available relevant evidence. Results Searches yielded ~1500 articles. These were included in structured reviews, yielding a total of 109 initial statements across seven physiological systems, and one patient-centred point of care (perioperative care). In addition to detailed PIMs statements (n=98), 11 statements address clinically important Potential Prescribing Omissions (PPOs) (e.g. anticoagulant underdosing) and altered blood pressure and glycaemic targets. Uniquely for criteria of this kind, 23 statements suggest PIMs be considered based on the different frailty levels, according to the Clinical Frailty Scale. 11/98 PIMs statements concern prescribing cascades and suggest tapering regimens for six inappropriate medication classes (e.g. antipsychotics, benzodiazepines). Several statements address medication appropriateness in other frailty related circumstances (e.g. non-compliance, overlapping co-morbidities, feeding tube incompatibility, pill burden/ polypharmacy). Conclusion Literature provides a large body of evidence to support prescribing optimization. This has been distilled into consensus-based statements, which should guide hospital-based health care professionals caring for frail older adults.

A RARE CAUSE OF MULTIFOCAL PNEUMONIA AND CONSTRICTIVE PERICARDITIS: COXSACKIEVIRUS A

A RARE CAUSE OF MULTIFOCAL PNEUMONIA AND CONSTRICTIVE PERICARDITIS: COXSACKIEVIRUS A

It Melts Like Snow: Steroid Responsiveness of Immunoglobulin G4-Related Disease

Dear Editor, A 35-year-old male presented with insidious onset gradually progressive bilateral painless submandibular swelling, followed by periorbital swelling [Figure 1] for the past 7 years. He had no constitutional or sicca symptoms. He had no history of addiction or autoimmunity in the family. Systemic examination was unremarkable. On evaluation, he had raised inflammatory markers with a negative autoimmune panel. Magnetic resonance imaging orbit showed bilateral orbital extraconal soft-tissue masses with contrast enhancement. Incisional biopsy from the extraconal mass was suggestive of fibrocollagenous stroma with aggregation of lymphocytes, plasma cells, and histiocytes without any necrosis or granuloma. On further evaluation, submandibular gland biopsy showed chronic sialadenitis with immunoglobulin G4 (IgG4)-positive plasma cell >10/hpf and IgG4: IgG ratio >40% [Figure 2] without any major organ involvement on imaging. The diagnosis of IgG4-related disease was kept. He was started on oral steroid 0.5 mg/kg/day and observed a rapid clinical response within 15 days of steroid therapy. Later, he was started on azathioprine and continued with tapering dose of steroid. He was followed up every month for first 3 months and then every 3 monthly upto 16 months without any signs of recurrence. For a long-standing indolent disease of 7 years, drastic steroid response with resolution of clinical symptoms was quite evident in our case.Figure 1: (a) Pretreatment bilateral upper eyelid swelling, (b) pretreatment bilateral submandibular swelling, (c and d) during glucocorticoid therapy (day 15) resolution of orbital and submandibular swelling, respectivelyFigure 2: Salivary gland with seromucinous acini and ducts embedded in mildly fibrotic stroma with numerous lymphoid follicles with germinal centers (a and b: H and E). Clusters of plasma cells are highlighted with CD138 immunohistochemical stain (c). IgG4 positive cells, >10/hpf (d)IgG4-related disease (IgG4-RD) is a chronic, systemic, fibroinflammatory condition with variable organ manifestation. CD4+ T-cells and B-cells are central to the pathogenesis causing organ damage and fibrosis. Marked expansion of IgG4-secreting plasmablast in the blood is usually seen in active and untreated cases.[1] Key to diagnosis is the classical histopathological hallmarks of lymphoplasmacytic infiltrate, storiform fibrosis, and obliterative phlebitis. IgG4 RD usually has a good response to steroids but a variable relapse rate. Factors associated with lesser treatment response and relapse were well analyzed in a Japanese multicenter study. Multivariate analysis from the study revealed that intermediate steroid initial dose (0.4–0.69 mg/day), slow tapering regimen (<0.4 mg/day), and shorter disease duration were associated with a significantly lower rate of disease relapse.[2] The study of isolated IgG4 ophthalmic disease also echoed similar results regarding steroid response and relapse, with more relapse in those with elevated serum IgG4 levels and a shorter duration of initial steroid treatment (<5 months). Low-dose steroid maintenance should be considered to avoid recurrence in patients with elevated serum IgG4 levels.[3] Later on, rituximab therapy showed promising results in inducing remission[4] and steroid-free long-term maintenance.[5] Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

2019 Research Grant. Does opioid tapering prior to spinal fusion improve surgical outcomes: a randomized controlled trial

<h3>BACKGROUND CONTEXT</h3> Preoperative opioid use in spine patients is associated with adverse patient-reported outcomes, higher rates of perioperative complications, increased postoperative opioid dependence, and greater surgical costs. <h3>PURPOSE</h3> The purpose of this study is to determine whether a structured preoperative opioid tapering regimen can successfully reduce postoperative opioid use and improve outcomes in spinal fusion surgery. <h3>STUDY DESIGN/SETTING</h3> Single center RCT. <h3>PATIENT SAMPLE</h3> To date, 12 patients enrolled (5 control, 7 taper). <h3>OUTCOME MEASURES</h3> Milligram morphine equivalent (MME) opioid use; back and leg numeric pain rating scale (NPRS); PROMIS (depression, anxiety, fatigue, sleep, satisfaction, physical function, pain interference, pain behavior); other medication use; intra- and perioperative outcomes; complications; subjective opiate withdrawal scale (SOWS). <h3>METHODS</h3> Patients undergoing thoracolumbar, lumbar, or lumbosacral spinal fusion surgery and taking opioids daily for 4 weeks prior to the preoperative planning visit were eligible for inclusion (buprenorphine and long-acting formulations excluded). Consenting patients were randomized to undergo a 4-week tapering program (reduction of 10% per week for a total of 40% prior to surgery) or to the control group. Patients were guided through the tapering process via weekly phone calls. Control patients also received weekly phone calls with the same outcomes administered, with the exception of the SOWS. All patients were followed postoperatively with weekly phone calls for 6 weeks, and via their 3- and 6-month postoperative visits. A preliminary analysis of the data to date was performed through data visualization and univariate statistics (a=0.5, SAS v9.4). <h3>RESULTS</h3> Initially, this study was powered conservatively for 78 patients. The COVID pandemic resulted in significant study disruptions and enrollment challenges. Patients, many of whom are seeking surgery for poorly controlled pain, were wary of tapering their opiate use, with the top reasons for study refusal including: (1) pain not well controlled, unwilling to risk randomization, (2) pain well controlled, unwilling to risk randomization, (3) Insufficient time, (4) no response after initial contact, and (5) unresponsive to any contact. For the 12 patients enrolled to date [50% female, median age 68 (range 49–74)]. The breakdown of opioids taken was: hydrocodone/acetaminophen 5 (41%), oxycodone/acetaminophen 3 (25%), tramadol 3 (25%), and oxycodone 1 (8%). All but 2 (16%) of patients used additional pain medications, most commonly acetaminophen (50%) and gabapentin (42%). The median number of levels fused in both groups was 5 (range control: 2-5, range experimental: 2-11). There were no obvious differences in baseline demographics, surgical approach, or analgesia. Total in-hospital MME was a median of 365 (IQR 143-395) for the control group and 295 (IQR: 189-322) for the taper group (p = 0.625). Three (60%) of the control group and 1 (15%) of the taper group required a pain consult (p = 0.222). None of the control group and 4 (57%) of the taper group had perioperative complications (p = 0.081). Control and taper patients had similar baseline NPRS pain; however, the taper group had lower back pain during the taper period (median back pain 1.5 to 6 points lower; p <0.05 for taper weeks 1 & 3; p <0.10 for taper weeks 2 and 4). Postoperative pain did not differ between groups. Visually, trends in leg pain were similar, but the variability was larger. No differences were evident in the PROMIS CATs between groups. During the taper period, none of the tapering patients experienced more than mild withdrawal symptoms. <h3>CONCLUSIONS</h3> Patients are hesitant to participate in preoperative opiate tapering, and the COVID epidemic further exacerbated these anxieties. In those patients who did taper, there is some evidence towards reduced preoperative pain and potentially lower in-hospital MMEs. To date, no differences are evident in postoperative PROMs. Enrollment of additional patients is ongoing, as is the analysis of pre- and postoperative MMEs. <h3>FDA DEVICE/DRUG STATUS</h3> This abstract does not discuss or include any applicable devices or drugs.

MO203: Minimal Change Disease Secondary to SARS-COV-2 (COVID-19) Infection: A Report of 2 Cases and Review of Related Literature

Abstract &amp;gt;BACKGROUND AND AIMS The COVID-19 pandemic has brought to the forefront a wide spectrum of renal injuries that included glomerulopathies, some of which were recently highlighted in various case reports. These consist of focal and segmental glomerulosclerosis (FSGS) and minimal change disease (MCD).1 These changes were found among seemingly vulnerable populations such as the African American and Caucasian ethnicities with paucity of reports among other races. We present two cases of biopsy-confirmed MCD secondary to COVID-19 infection among adult Filipino patients. METHODS Case Report RESULTS: Case 1 A 40-year-old Filipino female with a history of right total mastectomy 2 years prior for a low-grade phyllodes tumor and no other medical comorbidities was admitted due to stillbirth. She was noted to have bipedal edema with a positive COVID-19 RT-PCR swab. Further workup revealed a serum creatinine 1.04 mg/dL, urine RBC 1/HPF and a 24-h urine protein of 9.22 g with hypoalbuminemia and dyslipidemia. Serologic workup was noted to be negative. She was started on Losartan, Atorvastatin, and Furosemide. A kidney biopsy was performed which demonstrated unremarkable light microscopy and immunofluorescence and widespread podocyte-foot process effacement. These biopsy findings were interpreted to be consistent with minimal change disease. She was started on Prednisone at 1 mg/kg/day with continuation of both Losartan and Atorvastatin. Six weeks after, the patient achieved complete remission with resolution of both hypoalbuminemia and dyslipidemia. She also reports no further recurrence of edema. Case 2 A 61-year-old Filipino male with a history of type 2 diabetes mellitus, hypertension, dyslipidemia and mild COVID-19 infection 4 months prior now presented with diarrhea. A routine COVID-19 RT-PCR swab revealed a re-infection. Physical examination noted bipedal edema. Further workup demonstrated a serum creatinine 3.39 mg/dL, urine RBC 2/HPF and urine ACR 2.6 g/g. Serologic tests were negative. He was diagnosed with Nephrotic Syndrome and underwent kidney biopsy. Findings showed an unremarkable light microscopy and immunofluorescence with widespread podocyte-foot process effacement. These findings were found to be consistent with minimal change disease and acute tubular injury. He was started on Prednisone (1 mg/kg/day), Losartan, Furosemide and Atorvastatin. Eight weeks later, the patient achieved complete remission with resolution of edema. CONCLUSION It is currently suspected that APOL1 risk variants found in reported cases of COVID-19-associated glomerulopathies are underlying toxic gain-of-function mutations that drive kidney disease.2 It is interesting to note that APOL1 renal risk variants are found exclusively in African-derived chromosomes and are rarely found among European or Asian chromosomes.3 Even though an APOL1 genotyping was not performed, our case reports provide the first examples of MCD among individuals without a high-risk genotype (APOL1) by epidemiology and enlarge the literature on MCD in COVID-19. We posit that there may be other underlying predispositions or mechanisms that may be driving glomerulopathy formation among COVID-19 patients aside from their inherent APOL 1 risk. Both of our patients were started on steroid therapy with a tapering regimen and achieved complete remission on subsequent follow-up. Existing reports suggest that most cases of COVID-19-associated MCD will often achieve resolution of AKI and proteinuria with steroid therapy, even in those with high-risk APOL1 genotype, emphasizing the need for an accurate histologic classification.4

Defining optimal treatment for recurrent Clostridioides difficile infection (OpTION study): A randomized, double-blind comparison of three antibiotic regimens for patients with a first or second recurrence

BackgroundAlthough many large, randomized controlled trials (RCT) have been conducted on antibiotic therapy for patients with primary C. difficile infections (CDI), few RCTs have been performed for patients with recurrent CDI (rCDI). In addition, fecal microbial transplant (FMT) is neither FDA-approved or guideline-recommended for patients with pauci-rCDI (first or second recurrences). Therefore, a rigorous RCT of sufficient size was designed to determine the optimal treatment among three antibiotic regimens in current practice for treatment of pauci-rCDI. MethodsVA Cooperative Studies Program (CSP) #596 is a prospective, double-blind, multi-center clinical trial of veteran patients with pauci-rCDI comparing fidaxomicin (FDX) 200 mg twice daily for 10 days and vancomycin (VAN) 125 mg four times daily for 10 days followed by a 3-week vancomycin taper and pulse (VAN-T/P) regimen to a standard course of VAN 125 mg four times daily for 10 days. The primary endpoint is sustained clinical response at day 59, with sustained response measured as a diarrhea composite outcome (D-COM) that includes symptom resolution during treatment (before day 10) without recurrence of diarrhea or other clinically important outcomes through day 59. DiscussionCSP study 596 is designed to compare three current antibiotic treatments for recurrent CDI that are in clinical practice, but which lack high-quality evidence to support strong guideline recommendations. The design of the study which included a pilot phase initiated at six sites with expansion to 24 sites is described along with protocol modifications based on early trial experience and clinical realities including the COVID-19 pandemic.Trial Registration: This study is registered with clinicaltrials.gov (Identifier: NCT02667418).

Treatment of pemphigus in Australia: Aligning current practises with global recommendations.

Pemphigus encompasses of a group of rare, and often severe, intraepidermal bullous dermatoses that are mediated by autoantibodies that act against adhesion proteins of the desmosome. The current international consensus is that the use of intravenous CD20 inhibitors should be first-line in the management of moderate-to-severe cases of pemphigus, however Australia is yet to adopt this. Systemic corticosteroids, combined with conventional corticosteroid-sparing immunosuppressive agents such as azathioprine, mycophenolate mofetil, cyclosporin and methotrexate is still recommended as first-line therapy in Australia despite overwhelming evidence that combining rituximab with a rapid corticosteroid tapering regime is more effective in the treatment of moderate-to-severe pemphigus, and leads to fewer severe adverse effects. We propose a therapeutic approach that echoes the international consensus and recommend that rituximab, an anti-CD20 monoclonal antibody, be listed in the formularies of Australian Public Hospitals and on the Pharmaceutical Benefits Schemefor use in moderate to severe pemphigus.

Maintenance of Wellness in Patients With Obsessive-Compulsive Disorder Who Discontinue Medication After Exposure/Response Prevention Augmentation

Serotonin reuptake inhibitors (SRIs) are the only medications approved for obsessive-compulsive disorder (OCD), yet most patients taking SRIs exhibit significant symptoms. Adding exposure/response prevention (EX/RP) therapy improves symptoms, but it is unknown whether patients maintain wellness after discontinuing SRIs. To assess whether patients with OCD who are taking SRIs and have attained wellness after EX/RP augmentation can discontinue their SRI with noninferior outcomes compared with those who continue their SRI therapy. A 24-week, double-blind, randomized clinical trial was performed from May 3, 2013, to June 25, 2018. The trial took place at US academic medical centers. Participants included 137 adults with a principal diagnosis of OCD (≥1 year) who were taking an SRI (≥12 weeks), had at least moderate symptoms (defined as Yale-Brown Obsessive-Compulsive Scale [Y-BOCS] score ≥18 points), and received as many as 25 sessions of EX/RP therapy. Those who attained wellness (Y-BOCS score ≤14 points; 103 patients [75.2%]) were study eligible. Data were analyzed from June 29, 2019, to October 2, 2021. Participants were randomly assigned either to receive taper to placebo (taper group) or to continue their SRI (continuation group) and monitored for 24 weeks. The Y-BOCS score (range, 0-40 points) was the primary outcome; the Hamilton Depression Rating Scale (HDRS; range, 0-52 points) and the Quality-of-Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF; range, 0%-100%) scores were secondary outcomes. Outcomes were assessed at 8 time points by independent evaluators who were blinded to randomization. The taper regimen was hypothesized to be noninferior to continuation at 24 weeks using a 1-sided α value of .05. A total of 101 patients (mean [SD] age, 31.0 [11.2] years; 55 women [54.5%]) participated in the trial: 51 patients (50.5%) in the taper group and 50 patients (49.5%) in the continuation group. At 24 weeks, patients in the taper group had noninferior results compared with patients in the continuation group (mean [SD] Y-BOCS score: taper group, 11.47 [6.56] points; continuation group: 11.51 [5.97] points; difference, -0.04 points; 1-sided 95% CI, -∞ to 2.09 points [below the noninferiority margin of 3.0 points]; mean [SD] HDRS score: taper group, 5.69 [3.84] points; continuation group, 4.61 [3.46] points; difference, 1.08 points; 1-sided 95% CI, -∞ to 2.28 points [below the noninferiority margin of 2.5 points]; mean [SD] Q-LES-Q-SF score: taper group, 68.01% [15.28%]; continuation group, 70.01% [15.59%]; difference, 2.00%; 1-sided 95% CI, -∞ to 6.83 [below the noninferiority margin of 7.75]). However, the taper group had higher rates of clinical worsening (23 of 51 [45%] vs 12 of 50 [24%]; P = .04). Results of this randomized clinical trial show that patients with OCD who achieve wellness after EX/RP therapy could, on average, discontinue their SRI with noninferior outcomes compared with those who continued their SRI. Those who tapered the SRI had higher clinical worsening rates. Future research should evaluate if SRI half-life alters these rates. ClinicalTrials.gov Identifier: NCT01686087.

OP06 The influence of different prednisolone tapering algorithms on the effectiveness of infliximab in patients with Ulcerative Colitis – A real-world cohort study

Abstract Background Data regarding the influence of prednisolone tapering on clinical outcomes among patients with ulcerative colitis (UC) are limited. We aimed to investigate the influence of different prednisolone tapering algorithms on the effectiveness of infliximab (IFX) among patients with UC. Methods This Danish retrospective single-center study included all patients with UC who were treated with IFX between 2009 and 2019 at Herlev University Hospital. The patients were grouped according to the prednisolone tapering: standard (≤5 mg/week), fast (&amp;gt;5 mg/week), or direct discontinuation after an initial course of less than one week. Finally, we included a control group of patients treated with IFX monotherapy. The primary outcome was corticosteroid-free clinical remission at weeks 14 and 52 defined as a partial Mayo score ≤1. Variables with a p-value ≤0.20 in univariable regression analysis were included in multivariable analysis. A subgroup analysis containing patients with acute severe ulcerative colitis (ASUC) treated with at least 40 mg of prednisolone at initiation of IFX was performed. Results The study included 148 patients with UC of whom 81 (54.7%) were treated with prednisolone at the initiation of IFX. No association between prednisolone tapering and corticosteroid-free clinical remission with IFX at weeks 14 or 52 was observed (Figure 1 and Table 2). However, a higher proportion of patients in the standard tapering group achieved a C-reactive protein (CRP) level less than 5 mg/L at week 14 as compared with the fast-tapering group (23/23 (100%) vs. 14/18 (77.8%); p=0.03) and directly discontinuation group (6/10 (60%); p=0.03). This difference was not explained by prednisolone usage. In addition, none of the patients within the standard tapering regime (0/24; 0%) had severe activity at week 14 whereas this was seen in 4/19 (21.1%) in the fast tapering regime (p=0.03). In the subgroup analysis of 33 patients with ASUC, the standard tapering algorithm was associated with higher clinical remission as compared with the fast tapering regime at week 14 (9/14 (64.3%) vs. 5/19 (27.8%); p=0.02) and clinical response or remission at week 52 (12/14 (85.7%) vs. 7/19 (36.8%); p=0.01, Figure 2). Conclusion This study demonstrated no overall impact of prednisolone tapering algorithms on short and long-term effectiveness of IFX in patients with UC. However, standard tapering resulted in lower CRP levels and fewer cases of severe disease activity in the overall cohort and higher rate of short and long-term clinical response among ASUC patients, as compared with fast tapering regimes. Taken together, the data indicate that longer corticosteroid exposure in patients with high disease burden might improve IFX responses.

How to taper glucocorticoids in inflammatory rheumatic diseases? A narrative review of novel evidence in rheumatoid arthritis, systemic lupus erythematosus, and giant cell arteritis.

Glucocorticoids (GCs) remain regularly used drugs in patients with chronic inflammatory rheumatic diseases. As long-term intake at high dosages is associated with harm, it is generally advised that GCs be tapered and stopped. However, most recommendations concerning tapering have been eminence- or consensus-based. In this narrative review, we present novel data from recent studies (SEMIRA, CORTICOLUP, and GiACTA) shedding light from different angles on the effects of tapering GCs in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and giant cell arteritis (GCA). In RA and SLE, our main findings comprise that (a) the majority of RA and SLE patients can successfully taper their GC, but that (b) tapering increases the risk of flare. In GCA, tocilizumab was shown to be a potent GC-sparing agent. Finally, we also present exemplary tapering schemes for RA, SLE, and GCA, although different tapering regimens have not yet been sufficiently compared in randomized trials.

Early corticosteroid dose tapering in patients with acute exacerbation of idiopathic pulmonary fibrosis

BackgroundAlthough corticosteroid therapy with dose tapering is the most commonly used treatment for acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF), there is no consensus on the tapering regimen. This study aimed to investigate the association between early corticosteroid dose tapering and in-hospital mortality in patients with AE-IPF.MethodsIn this retrospective cohort study, we analyzed the data of a cohort from eight Japanese tertiary care hospitals and routinely collected administrative data from a cohort from 185 Japanese hospitals. Patients with AE-IPF were classified into the early and non-early tapering groups depending on whether the maintenance dose of corticosteroids was reduced within two weeks of admission. Propensity score analysis with inverse probability weighting (IPW) was performed to estimate the effect of early corticosteroid dose tapering.ResultsThe multi-center cohort included 153 eligible patients, of whom 47 (31%) died, whereas the administrative cohort included 229 patients, of whom 51 (22%) died. Patients with early tapering tended to have a better prognosis than those without it (unadjusted hazard ratio [95% confidence interval] 0.41 [0.22–0.76] and 0.65 [0.36–1.18] in the multi-center and administrative cohorts, respectively). After IPW, the early tapering group had a better prognosis than the non-early tapering group (IPW-adjusted hazard ratio [95% confidence interval] 0.37 [0.14–0.99] and 0.27 [0.094–0.83] in the multi-center and administrative cohorts, respectively).ConclusionEarly corticosteroid dose tapering was associated with a favorable prognosis in patients with AE-IPF. Further studies are warranted to confirm the effects of early corticosteroid dose tapering in patients with AE-IPF.

Systematic Review and Meta-Analysis: Efficacy of Vancomycin Taper and Pulse Regimens in Clostridioides difficile Infection

ABSTRACT Background Vancomycin is the drug of choice for treating Clostridioides difficile infection (CDI). We compare CDI resolution with vancomycin taper, pulse, and taper-and-pulse regimens. Methods We searched for Medline, Embase, Cochrane, and Scopus through October 9th, 2020. Taper regimen was defined as dose reduction over time; pulse was a regimen less frequent than daily. Studies assessing CDI resolution rates were included. Meta-analyses for resolution rates were performed using weighted proportion ratios (WPR). Results Ten studies with 675 patients treated with vancomycin regimens were included. Resolution rates were 83% (212/266, 95% CI 69–94%, I2 = 85%) for taper-and-pulse, 68% (264/383, 95% CI 57–78%, I2 = 72%) for taper alone, and 54% (11/26 95% CI 0–100%, I2 = 86%) for pulse alone regimens. Taper-and-pulse was superior to taper alone (WPR 83% vs 68%, p < 0.0001) and pulse alone (WPR 83% vs 54%, p < 0.0004), no significant difference between taper alone or pulse alone (WPR 68% vs 54%, p = 0.1). Conclusions Limitations of our analysis are a small number of included studies and heterogeneity. Vancomycin taper-and-pulse seems superior to pulse alone or taper alone for recurrent CDI. A randomized controlled trial comparing vancomycin taper-and-pulse to fidaxomicin and microbiome restoration is needed.

Old and New Calcineurin Inhibitors in Lupus Nephritis.

Calcineurin inhibitors (CNIs) are drugs that inhibit calcineurin, a key phosphatase that dephosphorylates a transcription factor called the nuclear factor of activated T cells (NFAT), allowing its translocation into the nucleus of quiescent T cells. In the nucleus, NFAT activates interleukin 2, which stimulates the proliferation and differentiation of T-cells. CNIs can also stabilize the actin cytoskeleton of podocytes reducing proteinuria. Thanks to these characteristics, CNIs have been often used in the treatment of autoimmune diseases. However, the therapeutic index of CNIs is narrow, and their interactions with other drugs can increase toxicity or reduce efficacy. In lupus nephritis, cyclosporine and tacrolimus have been used both in induction and maintenance therapies. Observational studies and randomized controlled trials showed that both cyclosporine and tacrolimus can increase efficacy. Tolerance is satisfactory if low doses are used and the patient is carefully monitored. More recently, a new CNI, called voclosporin (VCS), has been approved by the Food and Drug Administration for use in lupus nephritis. VCS offers potential advantages over other CNIs. In two large multiethnic trials, VCS was not associated with adverse renal and metabolic events and obtained positive results despite a novel and rapid corticosteroid tapering regime.

Prescribing in a pediatric hospital setting – Lost in translation?

ObjectivesTo determine parental understanding of directions on common pediatric prescription pharmacy labels and to identify enablers and barriers that affect interpretation of these labels. MethodsProspective qualitative descriptive study (July to August 2020) of 20 parents in post-surgical wards at a single Australian tertiary pediatric center. ResultsFour key themes emerged through inductive analysis of the interview transcripts: 1) the addition of specific directions, such as administration with/without food and treatment course duration were perceived to be beneficial; 2) explicit phrasing of dosing intervals and times were more easily interpreted; 3) the use of simpler and common terminology enhanced understanding of the directions; and 4) presentation of multiple-step directions (e.g. tapering regimens) in a simplified and more organized manner was identified as an enabler and was thought to reduce confusion. ConclusionDifferences in wording and presentation of pediatric prescription medication label directions led to variable interpretation by parents. Practise ImplicationsTherefore, there is a need for guidelines to standardize the wording of prescription medication advice labels. Findings from this study can be used to achieve this goal.

Efficacy and safety of secukinumab in patients with giant cell arteritis: study protocol for a randomized, parallel group, double-blind, placebo-controlled phase II trial

BackgroundOne key pathological finding in giant cell arteritis (GCA) is the presence of interferon-gamma and interleukin (IL)-17 producing T helper (Th) 1 and Th17 cells in affected arteries. There is anecdotal evidence of successful induction and maintenance of remission with the monoclonal anti-IL-17A antibody secukinumab. Inhibition of IL-17A could therefore represent a potential new therapeutic option for the treatment of GCA.MethodsThis is a randomized, parallel-group, double-blind, placebo-controlled, multi-center, phase II study in which patients, treating physicians, and the associated clinical staff as well as the sponsor clinical team are blinded. It is designed to evaluate efficacy and safety of secukinumab compared to placebo in combination with an open-label prednisolone taper regimen. Patients included are naïve to biological therapy and have newly diagnosed or relapsing GCA. Fifty patients are randomly assigned in a 1:1 ratio to receive either 300 mg secukinumab or placebo subcutaneously at baseline, weeks 1, 2 and 3, and every 4 weeks from week 4. Patients in both treatment arms receive a 26-week prednisolone taper regimen. The study consists of a maximum 6-week screening period, a 52-week treatment period (including the 26-week tapering), and an 8-week safety follow-up, with primary and secondary endpoint assessments at week 28. Patients who do not achieve remission by week 12 experience a flare after remission or cannot adhere to the prednisolone tapering will enter the escape arm and receive prednisolone at a dose determined by the investigator’s clinical judgment. The blinded treatment is continued. Two optional imaging sub-studies are included (ultrasound and contrast-media enhanced magnetic resonance angiography [MRA]) to assess vessel wall inflammation and occlusion before and after treatment. The primary endpoint is the proportion of patients in sustained remission until week 28 in the secukinumab group compared to the proportion of patients in the placebo group. A Bayesian approach is applied.DiscussionThe trial design allows the first placebo-controlled data collection on the efficacy and safety of secukinumab in patients with GCA.Trial registrationClinicalTrials.gov NCT03765788. Registration on 5 December 2018, prospective registration, EudraCT number 2018-002610-12; clinical trial protocol number CAIN457ADE11C.

P57. A double blind, randomized controlled, prospective trial assessing the effectiveness of oral corticoids in the treatment of symptomatic lumbar stenosis

P57. A double blind, randomized controlled, prospective trial assessing the effectiveness of oral corticoids in the treatment of symptomatic lumbar stenosis

P366 Vedolizumab maintenance therapy reduced use of corticosteroids in patients with Crohn’s disease in the GEMINI 2 trial

Abstract Background Corticosteroids (CSs) can induce clinical remission of Crohn’s disease (CD), but long-term use is associated with serious side effects. In the GEMINI 2 trial, a greater proportion of patients with moderately to severely active CD treated with vedolizumab (VDZ) maintenance therapy achieved CS-free remission at week 52 compared with placebo (PBO).1 Response to VDZ is influenced by prior exposure to anti-TNF therapy. In this post hoc exploratory analysis of GEMINI 2, we investigated the impact of VDZ maintenance therapy on use of CSs stratified by prior anti-TNF therapy failure status and baseline disease activity (moderate or severe). Methods In GEMINI 2, patients who responded to VDZ induction therapy at week 6 were re-randomized to receive VDZ or PBO every 4 or 8 weeks and began a prespecified CS tapering regimen (Figure 1).1 In patients receiving CSs at baseline, we measured change in CS dose from baseline to week 52 , proportion of patients with CS dose ≤ 7.5 mg/day, and proportion of patients with ≥ 90 or ≥ 180 consecutive CS-free days at week 52. Analyses were conducted overall and stratified by prior anti-TNF therapy failure status, baseline Crohn’s Disease Activity Index (CDAI) score (moderate: ≤ 330, severe: &amp;gt; 330), and the composite of both measures. Results In the overall population, a greater proportion of patients treated with VDZ (67.7%) vs PBO (61.5%) had their CS dose reduced from baseline. This trend was also observed among patients with no prior anti-TNF therapy failure, with a baseline CDAI score ≤ 330, and with no prior anti-TNF therapy failure and a baseline CDAI score ≤ 330 (Figure 2). Similarly, numerically higher proportions of patients treated with VDZ vs PBO received a CS dose of ≤ 7.5 mg/day in the overall population and in subgroups with no prior anti-TNF therapy failure, with baseline CDAI score ≤ 330, and with no prior anti-TNF therapy failure and a baseline CDAI score ≤ 330 (Figure 3). Overall, 35.2% and 32.7% of patients receiving VDZ had ≥ 90 and ≥ 180 consecutive CS-free days, respectively, compared with 28.0% and 22.0% of those receiving PBO. The proportion of patients with ≥ 180 consecutive CS-free days was numerically higher for the VDZ group vs the PBO group, regardless of prior anti-TNF therapy failure status or baseline CDAI score. Conclusion VDZ maintenance therapy was associated with more successful CS withdrawal than PBO, particularly in patients with no prior anti-TNF therapy failure and moderate disease activity. Interpretation of these results is limited by the exploratory nature of the analyses, small sample sizes and different initiation weeks for CS tapering per patient. Reference

AB0853 IGG4-RELATED DISEASE CAUSING OCULAR NERVE PALSIES AND ORBITAL APEX SYNDROME: CASE REPORT AND LITERATURE REVIEW

Background:IgG4-Related Disease (IgG4-RD) is a systemic immune-mediated fibroinflammatory condition. The epidemiology is not well defined: it usually affects adults from middle-age onwards, predominantly male. Both B and T-cells are central in IgG4-RD pathogenesis, as demonstrated by the efficacy of B-cell depletion therapy.IgG4-RD can affect multiple organs including the central and peripheral nervous system, producing a constellation of clinical symptoms and signs, depending on the organ structures involved.IgG4-related orbital disease is relatively rare can implicate all extra-ocular muscles, structures emerging from the Orbital apex, optic canal, or superior and inferior orbital fissure. Depending on the structures involved, it can produce different or sometimes subtle clinical presentations, posing diagnostic challenge. There were case reports of IgG4-related ophthalmic disease misdiagnosed as intraocular tumour.Objectives:IgG4-RD is increasingly recognised as an entity affecting the head and neck region. However, it rarely involves skull base and presents with orbital apex syndrome. In this current case report, we describe an interesting case of IgG-related orbital disease presenting with ocular nerve palsies and orbital apex syndrome.Methods:Case report.Results:A 36-year-old gentleman with cocaine and alcohol misuse presented with a 2-month history of left sided headache, diplopia, recurrent ear infections, otalgia and hearing loss. Initial imaging suggested left otomastoiditis and intravenous antibiotics were commenced. Contralateral partial third nerve palsy with pupil sparing was elicited. 2 months later, there was worsening right eye ptosis, proptosis, right relative afferent pupillary defect, reduced visual acuity and colour vision as well as a near-complete ophthalmoplegia. Subsequent imaging showed worsening soft tissue swelling centred on the upper left parapharyngeal and masticator space, with multiple perineural enhancement and lateral extension to right orbital apex and orbital fissures. Blood tests only revealed raised IgG4 subclass. Infectious aetiology was excluded. Left nasal mass biopsy performed showed no fungal organism or malignancy. There were lymphoplasmacytic proliferation but no storiform fibrosis or obliterative phlebitis. IgG4 immunostaining on two assessable fields revealed 22 and 17 positive plasma cells respectively, and an IgG4: IgG ratio of &lt;10%, and 50% in the other. Significant improvement was seen clinically and radiologically with antibiotics and a tapering regime of oral Prednisolone. Patient was commenced on Azathioprine as long term immunosuppression.Conclusion:A high degree of clinical suspicion is necessary to diagnose IgG4-RD when presenting with orbital apex syndrome and ocular nerve palsies,IgG4-RD can mimic mastoiditis of infectious aetiology. Other differentials may include cocaine-induced midline destructive lesions and granulomatosis with polyangiitis. The diagnosis can be supported by elevated serum IgG, elevated IgG index and pathognomonic histopathological findings. . The diagnosis of IgG4-related orbital disease should be deliberated on by a multidisciplinary group, with every effort being made to exclude an infectious aetiology, before embarking on immunosuppressive therapy.Primary treatment is with steroids. However, immunotherapy using azathioprine can be utilised in recurrent disease or patients with steroid intolerance.