Investigation of two treatment regimens in adults with mild asthma

<p>Introduction In adults with mild-moderate asthma, poor adherence to daily maintenance inhaled corticosteroids (ICS) leads to increased asthma symptoms and risk of asthma exacerbations. There is evidence that symptom-driven use of a combination ICS plus a fast-onset long-acting beta2-agonist (LABA) inhaler taken as needed may be an alternative to daily maintenance ICS plus as-needed short-acting beta2-agonists (SABA). Through four studies: The PRACTICAL study (a randomised controlled trial) and three sub-studies nested within it, this thesis aims to investigate the efficacy of as-needed ICS-formoterol (a fast-onset LABA), exposure to and patterns of ICS and beta2-agonist use, and patient preferences for and priorities concerning their asthma management. Methods The PRACTICAL study was a 52 week, open label, parallel group, multicentre, superiority, randomised controlled trial conducted at 15 sites throughout New Zealand. Adults aged 18-75 with a diagnosis of asthma who were taking SABA for symptom relief with or without low dose maintenance ICS were recruited. Participants were randomised 1:1 to either as-needed budesonide-formoterol (200/6mcg) one actuation for symptom relief or budesonide (200mcg) one actuation twice a day plus as-needed terbutaline (250mcg) two actuations for symptom relief. A sub-group of 110 participants had electronic inhaler monitors attached to their study inhalers which captured the time and date of every inhaler actuation. At their final study visit a total of 407 participants were eligible to complete a survey on their treatment preferences and experiences of their study randomised treatment, and a discrete choice experiment to determine their priorities for attributes of asthma management including; treatment regimen, shortness of breath, steroid dose and likelihood of an asthma flare-up. Results The PRACTICAL study found the rate of severe exacerbations per patient per year was lower in participants randomised to as-needed budesonide-formoterol than participants randomised to maintenance budesonide (absolute rate per patient per year 0.119 vs 0.172; relative rate 0.69; 95%CI 0.48-1.00; p=0.049). Within the electronic monitoring sub-study, exposure to ICS was significantly lower in the group randomised to as-needed budesonide-formoterol with a mean daily ICS dose of 176.0mcg versus 302.5mcg in those randomised to maintenance budesonide (difference -126.5mcg per day; 95%CI -171.0 to -81.9; p<0.001). Use of as-needed budesonide-formoterol was associated with extended periods of no ICS use (median 156 days vs 22 days respectively) and more days where ≥4, 6 or 8 actuations of ICS were taken than maintenance budesonide. Participants’ preference for either as-needed or maintenance treatment was strongly associated with randomised treatment; 90% randomised to as-needed budesonideformoterol preferred their randomised treatment compared to 60% of those randomised to maintenance budesonide, odds ratio for association between randomised treatment and preference was 13.3 (95%CI 7.1 to 24.7; p<0.001). The DCE found that amount of shortness of breath was the most important attribute of asthma treatment to all participants. However, the relative importance of other attributes, particularly type of treatment regimen, varied depending on whether the participants had previously stated a preference for as-needed or maintenance treatment. Discussion In adults with mild-moderate asthma, as-needed budesonide-formoterol is more effective at preventing severe asthma exacerbations than maintenance budesonide at a significantly lower exposure to ICS, despite long periods of no ICS use. This suggests that timing of ICS dose and titrating it in response to symptoms is more important than total dose. If participants have experienced as-needed budesonide-formoterol, they prefer it over maintenance budesonide suggesting this new approach to asthma treatment will be acceptable to patients. Control of shortness of breath was the most important attribute of asthma treatment to all patients. However, participants who preferred as-needed treatment were more willing to trade-off likelihood of an asthma flare up and steroid dose for their preferred treatment regimen. Knowledge of patient preferences and priorities for treatment, together with knowledge of regimen characteristics can be used in discussion with patients to determine the most appropriate regimen for them.</p>

Investigation of two treatment regimens in adults with mild asthma

<p>Introduction In adults with mild-moderate asthma, poor adherence to daily maintenance inhaled corticosteroids (ICS) leads to increased asthma symptoms and risk of asthma exacerbations. There is evidence that symptom-driven use of a combination ICS plus a fast-onset long-acting beta2-agonist (LABA) inhaler taken as needed may be an alternative to daily maintenance ICS plus as-needed short-acting beta2-agonists (SABA). Through four studies: The PRACTICAL study (a randomised controlled trial) and three sub-studies nested within it, this thesis aims to investigate the efficacy of as-needed ICS-formoterol (a fast-onset LABA), exposure to and patterns of ICS and beta2-agonist use, and patient preferences for and priorities concerning their asthma management. Methods The PRACTICAL study was a 52 week, open label, parallel group, multicentre, superiority, randomised controlled trial conducted at 15 sites throughout New Zealand. Adults aged 18-75 with a diagnosis of asthma who were taking SABA for symptom relief with or without low dose maintenance ICS were recruited. Participants were randomised 1:1 to either as-needed budesonide-formoterol (200/6mcg) one actuation for symptom relief or budesonide (200mcg) one actuation twice a day plus as-needed terbutaline (250mcg) two actuations for symptom relief. A sub-group of 110 participants had electronic inhaler monitors attached to their study inhalers which captured the time and date of every inhaler actuation. At their final study visit a total of 407 participants were eligible to complete a survey on their treatment preferences and experiences of their study randomised treatment, and a discrete choice experiment to determine their priorities for attributes of asthma management including; treatment regimen, shortness of breath, steroid dose and likelihood of an asthma flare-up. Results The PRACTICAL study found the rate of severe exacerbations per patient per year was lower in participants randomised to as-needed budesonide-formoterol than participants randomised to maintenance budesonide (absolute rate per patient per year 0.119 vs 0.172; relative rate 0.69; 95%CI 0.48-1.00; p=0.049). Within the electronic monitoring sub-study, exposure to ICS was significantly lower in the group randomised to as-needed budesonide-formoterol with a mean daily ICS dose of 176.0mcg versus 302.5mcg in those randomised to maintenance budesonide (difference -126.5mcg per day; 95%CI -171.0 to -81.9; p<0.001). Use of as-needed budesonide-formoterol was associated with extended periods of no ICS use (median 156 days vs 22 days respectively) and more days where ≥4, 6 or 8 actuations of ICS were taken than maintenance budesonide. Participants’ preference for either as-needed or maintenance treatment was strongly associated with randomised treatment; 90% randomised to as-needed budesonideformoterol preferred their randomised treatment compared to 60% of those randomised to maintenance budesonide, odds ratio for association between randomised treatment and preference was 13.3 (95%CI 7.1 to 24.7; p<0.001). The DCE found that amount of shortness of breath was the most important attribute of asthma treatment to all participants. However, the relative importance of other attributes, particularly type of treatment regimen, varied depending on whether the participants had previously stated a preference for as-needed or maintenance treatment. Discussion In adults with mild-moderate asthma, as-needed budesonide-formoterol is more effective at preventing severe asthma exacerbations than maintenance budesonide at a significantly lower exposure to ICS, despite long periods of no ICS use. This suggests that timing of ICS dose and titrating it in response to symptoms is more important than total dose. If participants have experienced as-needed budesonide-formoterol, they prefer it over maintenance budesonide suggesting this new approach to asthma treatment will be acceptable to patients. Control of shortness of breath was the most important attribute of asthma treatment to all patients. However, participants who preferred as-needed treatment were more willing to trade-off likelihood of an asthma flare up and steroid dose for their preferred treatment regimen. Knowledge of patient preferences and priorities for treatment, together with knowledge of regimen characteristics can be used in discussion with patients to determine the most appropriate regimen for them.</p>

Tacrolimus as Single-Agent Immunotherapy and Minimal Manifestation Status in Nonthymoma Myasthenia Gravis

Background. Tacrolimus is a second-line immunosuppressant in myasthenia gravis (MG) therapy, which is mainly used in combination with corticosteroids to reduce steroid dose and maintain the effect of immunotherapy. However, few studies have focused on the effect of tacrolimus as single-agent immunotherapy on achieving minimal manifestation status (MMS). Thus, this study is aimed at exploring the efficacy and influencing factors of tacrolimus as single-agent immunotherapy in MG. Methods. Clinical data of 75 nonthymoma MG patients treated with tacrolimus single-agent as initial immunotherapy were retrospectively analyzed. The therapeutic effect was evaluated by Myasthenia Gravis Foundation of America postintervention status. Clinical factors affecting the achievement of MMS and treatment reactivity of different MG subtypes were determined by Cox regression analysis. Results. Tacrolimus was generally safe, with only two patients (2.7%) switching medications due to side effects. 32% of patients had improved symptoms after 1 month of treatment. 69.2% of patients achieved MMS or better after one year. The age < 39 years old, QMG score < 11 points, and AChR − Ab titer < 8.07 nmol / L were indicative of a favorable response, which was independent of gender, course of the disease. As for MG subtypes, ocular and seronegative MG showed better treatment sensitivity. Conclusions. Tacrolimus as single-agent immunotherapy takes effect quickly and can effectively enable nonthymoma MG patients to achieve MMS. Tacrolimus can be used alone for the initial immunotherapy of MG patients, especially for young, mild, and low antibody titer patients.

Propensity Score Matching Analysis Comparing Extracorporeal Photopheresis (ECP) Vs Best Available Therapy in Third Line or Later Treatment of Chronic Graft-Versus-Host Disease (cGVHD)

*DB and DK contributed to the work equally Background Prospective randomized controlled data comparing extracorporeal photopheresis (ECP) to other treatments for chronic graft vs host disease (cGvHD) as third-line or later therapy are limited, despite its clinical benefit observed in patients (pts) who failed ≥ 2 lines of previous therapy. Our single-center experience has reported promising results, including 68.3% failure-free survival (FFS) and 85.9% overall survival (OS) at 12 months in 75 heavily pre-treated cGvHD pts treated with ECP (ASH 2021 Abstract ID 152640). The present study compared outcomes, using propensity-score matching (PSM), between ECP ("ECP group", n=74) and a historical cohort treated with best available therapy (BAT) as third-line or later treatment from 2007 to 2021 ("BAT group", n=132). Statistical endpoints such as FFS and OS, as well as steroid dose reduction were evaluated instead of overall response due to limited response assessment data available from retrospective chart review. Patients and methods The BAT group received MMF (n=71, 53.8%), prednisone (n=37, 28.0%), prednisone/cyclosporine (n=7, 5.3%), rituximab (n=7, 5.3%), and others (n=10, 7.6%). There was an imbalance in characteristics between the two groups, as expected; the ECP group had more pts with severe cGVHD (91.1% vs 20.5%; p&lt;0.001), fewer with a previous history of acute GVHD (aGvHD: 60.8% vs 78.0%; p=0.008), and fewer on a prednisone dose ≥0.5mg/kg/day (37.8% vs. 90.5%; p&lt;0.001). PSM analysis was applied to adjust risk factors imbalanced between groups, including cGVHD grade (mild/moderate vs severe), aGVHD history, and baseline prednisone dose (&lt;0.5 vs. ≥ 0.5 mg/kg/day). A total of 54 pts (27 case-control pairs) were selected via PSM within 0.2 of a calliper difference, resulting in the balancing of risk factors between groups: cGVHD severity (p=0.941), aGVHD history (p=0.75) and prednisone dose ≥ 0.5 mg/kg/day (p=0.788). FFS and OS were calculated from the day of starting ECP or BAT, and were compared using Cox's hazard model. Daily prednisone dose at months 0, 3 and 6 were calculated divided by body weight (kg), and the proportions of pts on prednisone ≤ 0, 0.1, 0.2 and 0.5mg/kg/day were compared. Results In the overall cohort (n=206), with a median 29 months of follow-up, 114 treatment failures (55.3%) occurred. While the non-relapse mortality (NRM) was similar in both groups, the ECP group showed a lower rate of resistance requiring therapy switch. Failure was noted in 27 ECP pts (36.4%) due to causes including resistance/intolerance requiring a switch to other therapy (n=15; 20.3%), NRM (n=11, 14.8%), and relapse (n=1; 1.4%), while 87 failures (65.9%) were noted in BAT pts due to resistance requiring a switch to other therapy (n=63; 47.7%), NRM (n=7; 5.3%), and relapse (n=17; 12.9%). In the overall cohort, the 12-month FFS was 68.3% and 32.0% in ECP and BAT groups (p&lt;0.0001; Fig 1A), while OS was 86.2% and 82.2% in ECP and BAT groups, respectively (p=0.333; Fig 1B). In the PSM cohort (n=54), the ECP group showed a survival benefit at 12 months: FFS was 65.8% in the ECP group vs. 30.5% in the BAT group (p=0.00226; Fig 2A), and OS was 76.6% in the ECP group vs. 67.1% in the BAT group (p=0.0977; Fig 2B). Multivariate analysis in the PSM cohort confirmed that ECP was superior to BAT for FFS (p=0.024, HR 0.317 [0.117-0.859]) when adjusted for other risk factors including cGVHD severity, aGvHD history, age, HCT-CI score and prednisone dose ≤0.5mg/kg/day. Prednisone doses were gradually reduced over time; the median doses of prednisone at months 0, 3, and 6 were 0.35, 0.22 and 0.11 mg/kg/day, respectively, in the ECP group vs. 0.96, 0.24 and 0.19mg/kg/day in the BAT group. ECP also showed better kinetics of steroid dose reduction over time; the proportions of pts who discontinued prednisone at months 0, 3 and 6 were 16.2, 17.6% and 32.4% in ECP group vs. 0.8%, 0% and 2.5% in BAT group (Fig 3). The differences in the proportion of pts (delta) who discontinued prednisone in the ECP vs. BAT groups were 15.4%, 17.6% and 29.9% at 0, 3, and 6 months, respectively. Conclusion In the current study using PSM analysis, use of ECP was associated with a superior FFS to BAT when used as third-line or later therapy in cGVHD patients who failed at least 2 lines of previous therapy. Use of ECP also allowed for better steroid tapering in comparison to BAT. Figure 1 Figure 1. Disclosures Patriquin: Alexion: Consultancy, Honoraria, Speakers Bureau; BioCryst Pharmaceuticals: Honoraria; AstraZeneca: Consultancy, Honoraria, Speakers Bureau; Apellis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria. Law: Novartis: Consultancy; Actinium Pharmaceuticals: Research Funding. Lipton: Bristol Myers Squibb, Ariad, Pfizer, Novartis: Consultancy, Research Funding. Mattsson: MattssonAB medical: Current Employment, Current holder of individual stocks in a privately-held company. Kim: Novartis: Consultancy, Honoraria, Research Funding; Paladin: Consultancy, Honoraria, Research Funding; Bristol-Meier Squibb: Research Funding; Pfizer: Honoraria.

Impact of Corticosteroids on Efficacy of BCMA Targeted CAR-T Therapy in Multiple Myeloma

Background: B-cell maturation antigen (BCMA) directed chimeric antigen receptor T-cell therapy (CAR-T) has shown unprecedented efficacy in multiple myeloma (MM). CAR-T toxicities in the acute period, cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and macrophage activation syndrome (MAS) are managed by tocilizumab, steroids, and/or anakinra. However, since steroids have been shown to inhibit T cell activity (Ashwell et al. 2000), their use to mitigate these toxicities may have deleterious effects on CAR-T efficacy. Previous studies which examined steroid effects on CAR-T therapy in other hematologic malignancies have shown mixed results (Liu et al. 2020, Strati et al. 2021, Topp et al. 2019). We performed a single-center retrospective analysis of steroid use in MM patients (pts) during BCMA CAR-T hospitalization. Methods: All patients treated at UCSF with a BCMA CAR-T for MM from 11/1/2017-3/31/2021 were analyzed for steroid use during CAR-T hospitalization and treatment outcomes. Per institutional policy, all CAR-T pts were hospitalized for at least 14 days post-CAR-T infusion. Baseline pt characteristics, steroid usage, CAR-T toxicities and its treatment were collected. Overall response rate (ORR) was determined according to International Myeloma Working Group criteria. Overall survival (OS), progression-free survival (PFS) and time-to-next treatment (TTNT) were summarized using Kaplan-Meier methods and compared using log-rank tests. Wilcoxon rank-sum and Fisher's exact tests were used to compare continuous and categorical variables, respectively. Results: Of the 62 CAR-T pts, 24 (38.7%) received steroids during CAR-T hospitalization. Fifteen (62.5%), 5 (20.8%), 1 (4.2%) and 3 (12.5%) pts were given steroids respectively for CRS only, CRS and ICANS, CRS and MAS, or ICANS only. CAR-T toxicities included: 52 pt with CRS (27 gr 1, 25 gr 2); 8 pt with ICANS (3 gr 1, 3 gr 2, 2 gr 3) and 9 pt with MAS (3 gr 1, 2 gr 2, 3 gr 3, 1 gr 4). All pts received only dexamethasone (dex) except for 1 for whom solumedrol was converted into dex equivalent units. Median time to steroid initiation after CAR-T infusion was 2 days (0-10), median total days on steroids was 4 (1-10), and median cumulative steroid dose was 60mg (10-498). Overall, the results showed no significant difference in ORR (95.8% v 84.2, p=0.2), PFS (13.1 v 13.2 mo, p=0.9) (Fig. 1A), OS (not reached (NR) v 26.4 mo, p=0.5) (Fig. 1B) or TTNT (10.5 v 7.0, p=0.3) when pts received steroids compared to no steroids. There were also no significant differences in ORR, PFS, OS, or TTNT based on cumulative dose of steroid received. Pts given 0 v ≤ 60 v &gt; 60mg cumulative steroid dose had ORR of 84.2%, 100%, 90.9% (p=0.4) and median PFS of 13.2, 15.7 and 13 mo (p=0.5) (Fig. 1C), respectively. Similarly, median OS (Fig. 1D) and TTNT was 26.3 mo, NR, NR (p=0.6) and 22.8, 17.5, 15.1 mo (p=0.6) for the three groups, respectively. Pts who received steroids for 0 vs 1-5 vs ≥5 days had ORR of 84.2%, 100% and 85.7% (p=0.2). There was no statistically significant difference in median PFS (13.2, 21.4, and 10.6 mo (p=0.05)) (Fig. 1E) or median OS (26.4, NR, and 24.8 mo (p = 0.2)) (Fig. 1F). Median TTNT was statistically significant at 22.8, 24.6, and 12.5 mo (p = 0.04). Median length of hospitalization was 14 days for both steroid-treated and non-steroid treated pts. Median disease burden (as measured by pre-CAR-T serum free light chains (SFLC)) also did not differ based on steroid treatment (195.9 mg/L vs 207.5 mg/L, p=0.9). Median follow-up time for the whole cohort was 19.0 mo (range 1.2-42.9). Forty-three (69%) pts died and 36 (58%) pts progressed through CAR-T. Lastly rates and timing of CRS, ICANS, and MAS, as well as tocilizumab and anakinra doses, initiation dates, and duration were not significantly associated with worsened ORR, PFS or OS. Pts with a high (&gt;207.5 mg/L) pre-CAR-T SFLC were associated with a shortened PFS (10.6 v 35 mo, p=0.002) (Fig. 2A), OS (24.2 mo v NR, p=0.07) (Fig. 2B) and TTNT (11.9 v 41.4 mo, p=0.002) compared to those with low disease burden (≤207.5 mg/L). Conclusions: In conclusion, our retrospective study showed that steroid use in general is not significantly associated with worsened ORR, PFS, OS, and TTNT in pts receiving BCMA targeted CAR-T for MM. There may be an impact on PFS and TTNT when the total time on steroids is ≥ 5 days. Future larger studies are needed to examine the effect of steroid exposure and duration on BCMA CAR-T efficacy. Figure 1 Figure 1. Disclosures Lo: Oncopeptides: Consultancy; EUSA Pharma: Consultancy. Martin: GlaxoSmithKline: Consultancy; Amgen: Research Funding; Janssen: Research Funding; Oncopeptides: Consultancy; Sanofi: Research Funding. Wolf: Adaptive Biotechnologies: Consultancy; Teneobio: Consultancy; Sanofi: Consultancy; Amgen: Consultancy. Chung: Caelum: Research Funding. Shah: Nektar: Research Funding; Oncopeptides: Consultancy; Poseida: Research Funding; Kite: Consultancy; Sanofi: Consultancy; Sutro Biopharma: Research Funding; Janssen: Research Funding; Karyopharm: Consultancy; Precision Biosciences: Research Funding; Indapta Therapeutics: Consultancy; GSK: Consultancy; CSL Behring: Consultancy; CareDx: Consultancy; BMS/Celgene: Research Funding; Bluebird Bio: Research Funding; Amgen: Consultancy; Teneobio: Research Funding. Wong: Amgen: Consultancy; Genentech: Research Funding; Fortis: Research Funding; Janssen: Research Funding; GloxoSmithKlein: Research Funding; Dren Biosciences: Consultancy; Caelum: Research Funding; BMS: Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees.

Single Centre, Retrospective Analysis of Extracorporeal Photopheresis (ECP) Therapy in the Patients Who Are Heavily Pre-Treated for Steroid Resistant Chronic Graft-Versus-Host Disease (GVHD)

*DB and DK contributed to the work equally. Background Extracorporeal photopheresis (ECP) is a recommended second or later line of therapy for chronic GVHD (cGVHD), and is beneficial not only because of increased response but also for its lack of adverse effects, specifically systemic immune suppression, mainly from steroids. In this single centre study, we attempted to evaluate not only therapeutic efficacy of ECP, but also its steroid-sparing effect by regularly analyzing steroid dose per body weight. We also attempted to identify any predictors of response or survival after ECP, which was not well defined before. Patients and methods A total of 75 cGVHD patients (pts) who received ECP for cGVHD from 2007 to 2021 at Princess Margaret Cancer Centre were included and evaluated retrospectively. Patients and disease characteristics are as follows: median age 48.5 years (range 17-70); male 42/75 (56%); organ involvement at the time of ECP: skin (93%), oral (53%), eye (51%), gastrointestinal (25%), liver (49%), lung (57%), and musculoskeletal (n=50, 67%). Sixty-eight (91%) and 7 pts (9%) had severe and moderate grade cGVHD, respectively. Sixty-eight pts (91%) received ECP as 4 th line or beyond. They were heavily pretreated with prednisone (98%), cyclosporine (57%), tacrolimus (24%), mycophenolate mofetil (64%), azathioprine (65%), rituximab (7%), imatinib (8%), ibrunitib (3%) and ruxolitinib (1%). ECP was started twice weekly for the first 12 weeks, then twice every 2 weeks in 2012-2021, while the schedule was twice every 2 weeks from 2007-2012. If there was no response or clinical benefit noted in first 24 treatments, then ECP was discontinued. In general, we attempted to provide up to around 60 sessions based on the clinicians' discretion. The overall response rate (ORR) and clinical benefit (CB) were assessed at months 3, 6 and 12 after staring ECP. As part of standard clinical practice, NIH consensus criteria were used for grading and response assessment. CB was assessed considering clinical response as well as steroid dose reduction. Treatment failure was defined as 1) resistance to ECP requiring treatment switch, 2) non-relapse mortality (NRM), 3) relapse, 4) intolerance to ECP. Failure free survival (FFS) and overall survival (OS)were calculated from the day of ECP initiation until the endpoints of failure or death, respectively. Results ECP was started a median of 28 months (range 1-125) after development of cGVHD. ECP was performed a median of 35 times (range 6-174) with a median duration of 11 months (range 1-53). Out of 75 pts, 48 completed planned ECP successfully and 27 stopped due to no response or benefit including, of whom 14 required additional therapy, 1 stopped due to line infection, and 1 stopped due to relapse of AML. With a median 72 months of follow-up, ORR was attained in 21% (16/75), 57% (36/63) and 70% (32/46) at month 3, 6 and 12, respectively. At 6 months, ORR was observed in 47-64% across all organs assessed. No difference in ORR was noted according to the cGVHD grade; at 6 months, severe cGVHD showed similar ORR (57%) to those with moderate cGVHD (60%) (p=0.893). CB was noted in 23% (17/75), 62% (39/63), and 76% (35/46) at month 3, 6 and 12, respectively. A total of 27/75 failures (36%) and 20/75 death (27%) occurred, due to the following: ECP resistance requiring switch to other therapy (n=14, 19%), NRM (n=11, 15%), relapse of primary disease (n=1, 1%) or ECP-related complication (n=1, 1%, line infection). In the overall cohort, FFS and OS at 12 months were 68.3% and 85.9%, respectively (Figure 1). More than a half of pts stopped steroids completely within 12 months after starting ECP. The proportion of pts off steroids was 16%, 17%, 32%, and 64% at month 0, 3, 6 and 12 after starting ECP, respectively (Figure 2). Risk factor analysis did not show any predictive markers for ORR at 6 months, while prognostic factor analysis suggested the development of musculoskeletal involvement as favorable prognostic factor for FFS (p=0.003, HR 0.315 [0.147, 0.673]) even with multivariate analysis. Conclusion Our study showed that: 1) ECP is a very effective treatment for heavily pre-treated cGVHD pts who have failed other therapies; 2) More than a half of pts can stop steroids completely within 12 months after starting ECP, thus avoiding long-term toxicity risk. Further study is warranted comparing ECP with other cGVHD treatment modalities. Figure 1 Figure 1. Disclosures Patriquin: BioCryst Pharmaceuticals: Honoraria; Alexion: Consultancy, Honoraria, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Speakers Bureau; Apellis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria. Law: Novartis: Consultancy; Actinium Pharmaceuticals: Research Funding. Lipton: Bristol Myers Squibb, Ariad, Pfizer, Novartis: Consultancy, Research Funding. Mattsson: MattssonAB medical: Current Employment, Current holder of individual stocks in a privately-held company. Kim: Paladin: Consultancy, Honoraria, Research Funding; Bristol-Meier Squibb: Research Funding; Pfizer: Honoraria; Novartis: Consultancy, Honoraria, Research Funding.

Mycophenolate Mofetil for a Flare Child Lupus Nephritis: A Case Reports

Renal involvement is the most common complication of systemic lupus erythematosus(SLE) and is also an important predictor of patient mortality. The incidence of flaresis estimated at 65% each year in patients with lupus nephritis. Therapy in lupusnephritis with flare also uses high doses of steroid agents and strongimmunosuppression agent. Mycophenolate mofetil (MMF) as a immunosuppressionagent tends to favor for flare in lupus nephritis. We describe a patient who had flarein lupus nephritis that resolved with high-dose steroid and MMF. The combination ofimmunosuppression agent and high-dose corticosteroid is an effective for control ofactive diseases. Cyclophosphamide as the steroid sparing agent was discontinuedbecause of adverse effect as well as hematuria. Partial remission was later achievedand maintained with MMF and corticosteroid after five month with protocol treatment.Thus, MMF while maintaining the steroid dose may induce remission for this case.

Distinct patterns of disease activity over time in patients with active SLE revealed using latent class trajectory models

Background Systemic lupus erythematosus (SLE) is a heterogeneous systemic autoimmune condition for which there are limited licensed therapies. Clinical trial design is challenging in SLE due at least in part to imperfect outcome measures. Improved understanding of how disease activity changes over time could inform future trial design. The aim of this study was to determine whether distinct trajectories of disease activity over time occur in patients with active SLE within a clinical trial setting and to identify factors associated with these trajectories. Methods Latent class trajectory models were fitted to a clinical trial dataset of a monoclonal antibody targeting CD22 (Epratuzumab) in patients with active SLE using the numerical BILAG-2004 score (nBILAG). The baseline characteristics of patients in each class and changes in prednisolone over time were identified. Exploratory PK-PD modelling was used to examine cumulative drug exposure in relation to latent class membership. Results Five trajectories of disease activity were identified, with 3 principal classes: non-responders (NR), slow responders (SR) and rapid-responders (RR). In both the SR and RR groups, significant changes in disease activity were evident within the first 90 days of the trial. The SR and RR patients had significantly higher baseline disease activity, exposure to epratuzumab and activity in specific BILAG domains, whilst NR had lower steroid use at baseline and less change in steroid dose early in the trial. Conclusions Longitudinal nBILAG scores reveal different trajectories of disease activity and may offer advantages over fixed endpoints. Corticosteroid use however remains an important confounder in lupus trials and can influence early response. Changes in disease activity and steroid dose early in the trial were associated with the overall disease activity trajectory, supporting the feasibility of performing adaptive trial designs in SLE.