Maintenance Therapy In Patients Research Articles

Comparing R-Bendamustine vs. R-CHOP Plus Maintenance Therapy as First-Line Systemic Treatment in Follicular Lymphoma: A Multicenter Retrospective GELTAMO Study.

Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and R-bendamustine (R-B) are the most common frontline treatment strategies for advanced-stage follicular lymphoma (FL). After R-CHOP induction therapy, using rituximab for maintenance therapy notably improves outcomes; however, whether this can be achieved by using the same approach after R-B therapy is still being determined. This retrospective analysis compared 476 FL patients from 17 GELTAMO centers who received R-based regimens followed by rituximab maintenance therapy for untreated advanced-stage FL. The complete response rate at the end of induction was higher with R-B and relapses were more frequent with R-CHOP. During induction, cytopenias were significantly more frequent with R-CHOP and so was the use of colony-stimulating factors. During maintenance therapy, R-B showed more neutropenia and infectious toxicity. After a median follow-up of 81 months (95% CI: 77-86), the 6-year rates of progression-free survival (PFS) were 79% (95% CI: 72-86) for R-bendamustine vs. 67% (95% CI: 61-73) for R-CHOP (p = 0.046), and 6-year overall survival (OS) values were 91% (95% CI: 86-96) for R-B vs. 91% (95% CI: 87-94) for R-CHOP (p = 0.49). In conclusion, R-B followed by rituximab maintenance therapy in patients with previously untreated FL resulted in significantly longer PFS than R-CHOP, with older patients also benefiting from this treatment without further toxicity. Adverse events during maintenance were more frequent with R-B without impacting mortality.

Abstract 5261: Immunologic signatures of peripheral blood cells in patients with advanced pancreatic cancer under lenvatinib-pembrolizumab maintenance therapy

Abstract Background: The treatment of pancreatic cancer is limited by chemotherapy toxicities which impacts quality of life. This is a phase 2 clinical trial of lenvatinib and pembrolizumab as maintenance therapy in patients with advanced pancreatic cancer. We observed preclinical activity of this combination in pancreatic mouse models. We hypothesize that this combination may address unmet needs to minimize toxicities associated with standard treatments, stimulate anti-tumor T cell immunity, and improve the progression free and overall survival. Exploratory studies aim to characterize immune-related systemic changes in peripheral blood over the course of therapy and to identify global changes in expression of tumor-related genes in needle biopsy samples of liver metastatic lesions. Methods: Multiplex gene expression analysis of unsorted peripheral blood mononuclear cells (PBMC) was performed using PanCancer Immune Profiling Panel on NanoString nCounter platform. PBMC samples from pre- through week 32 of treatment were assessed for differential expression of 730 immune profiling genes defining T cell functions and associated immune categories. Results: PBMC immune profiling from 4/5 patients show a distinctive pattern of increased activation of T cells during the first 9 weeks of treatment followed by a sharp inhibition starting at weeks 9-12 after 3-4 cycles of treatment (CD3E, CD247, LCK, TBX1, TCF7, STAT4, IL2RG). Subsequent upregulation of macrophage-derived scavenger, inflammatory, and immunosuppressive gene expression patterns continued for the remainder of treatment (CD14, MSR1, MARCO, CD68, TGFB1, IL10RA). The median PFS of first 10 patients was 21.5 (9-32) weeks. Conclusions: Immunotherapy resistance may be related to rapidly developing terminal differentiation and unresponsiveness of T cells in parallel with upregulation of macrophage-derived inflammatory and immunosuppressive processes. Studies are on-going to prevent inhibition of the T-cells. Citation Format: Vincent Chung, Ferdynand Kos, Edwin Manual, Shannon Dempsey, Don J. Diamond. Immunologic signatures of peripheral blood cells in patients with advanced pancreatic cancer under lenvatinib-pembrolizumab maintenance therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5261.

Long-Term Safety and Effectiveness of Tacrolimus in Patients With Lupus Nephritis in Japan: 10-Year Analysis of the Real-World TRUST Study.

To assess the long-term safety and effectiveness of tacrolimus as maintenance therapy in patients with lupus nephritis (LN) receiving treatment in real-world clinical settings in Japan. An open-label, noncomparative, observational, prospective postmarketing surveillance study was conducted in 1395 patients with LN receiving maintenance treatment with tacrolimus at 278 medical institutions across Japan over a period of 10 years. Tacrolimus continuation rate and cumulative incidence of adverse drug reactions (ADRs), relapse, progression to renal failure, and progression to dialysis were calculated using Kaplan-Meier analysis. Safety data were available for 1355 patients, almost half (49.3%) of whom remained on tacrolimus for the full 10 years of follow-up. A significant reduction in mean (SD) daily oral corticosteroid dose was observed from 16.0 (9.7) mg/day at 4 weeks after initiation of tacrolimus treatment to 7.2 (4.4) mg/day at year 10 (P < 0.001). The most frequently reported serious ADRs were infections (reported for 131 [9.7%] patients). Except for infections, no marked increase in the incidence of any other ADRs was seen over time, including renal impairment, malignant tumors, and cardiac dysfunction. Renal function was generally well maintained over the 10 years of follow-up. At year 10, cumulative rates of relapse, renal failure, and dialysis were 44.5%, 12.2%, and 4.5%, respectively. Tacrolimus was effective and generally well tolerated as maintenance therapy for LN in a large cohort of patients in Japan followed for 10 years, almost half of whom remained on therapy for the entire duration of follow-up. (ClinicalTrials.gov: NCT01410747).

Health-related quality of life and quality-adjusted progression free survival for carfilzomib and dexamethasone maintenance following salvage autologous stem-cell transplantation in patients with multiple myeloma: a randomized phase 2 trial by the Nordic Myeloma Study Group

BackgroundDecisions regarding maintenance therapy in patients with multiple myeloma should be based on both treatment efficacy and health-related quality of life (HRQL) consequences. In the CARFI trial, patients with first relapse of multiple myeloma underwent salvage autologous stem cell transplantation (salvage ASCT) before randomization to carfilzomib-dexamethasone maintenance therapy (Kd) or observation. The primary clinical endpoint was time to progression, which was extended by 8 months by Kd. The aim of this paper is to present the all HRQL endpoints of the CARFI trial including the HRQL effect of Kd maintenance therapy relative to observation. The primary HRQL endpoint was assessed by EORTC QLQ-C30 Summary score (QLQ-C30-sum) at 8 months follow-up. A key secondary HRQL endpoint was quality-adjusted progression-free-survival (QAPFS).MethodsHRQL was assessed with EORTC QLQ-C30, EORTC QLQ-MY20 and FACT/GOG-Ntx at randomization and every second month during follow-up. HRQL data were analyzed with linear mixed effect models until 8 months follow-up. QAPFS per individual was calculated by multiplying progression-free survival (PFS) by two quality-adjustment metrics, the QLQ-C30-sum and EORTC Quality of Life Utility Measure-Core 10 dimensions (QLU-C10D). The QAPFS per treatment group was estimated with the Kaplan-Meier method. P < 0.05 was used for statistical significance, and a between-group minimal important difference of 10 points was interpreted as clinically relevant for the QLQ-C30-sum.Results168 patients were randomized. HRQL questionnaire compliance was 93%. For the QLQ-C30-sum, the difference of 4.62 points (95% confidence interval (CI) -8.9: -0.4, p = 0.032) was not clinically relevant. PFS was 19.3 months for the Kd maintenance group and 16.8 months for the observation group; difference = 2.5 months (95% CI 0.5; 4.5). QAPFS based on the QLQ-C30-sum for the Kd maintenance group was 18.0 months (95% CI 16.4; 19.6) and for the observation group 15.0 months (95% CI 13.5; 16.5); difference = 3.0 months (95% CI 0.8–5.3). QAPFS based on the QLU-C10D for the Kd maintenance group was 17.5 months (95% CI 15.9; 19.2) and 14.0 months (95% CI 12.4; 15.5) for the observation group; difference = 3.5 months (95% CI 1.1–5.9).ConclusionsKd maintenance therapy after salvage ASCT did not adversely affect overall HRQL, but adjustment for HRQL reduced the PFS compared to unadjusted PFS. PFS of maintenance therapy should be quality-adjusted to balance the benefits and HRQL impact.

OP06 Risankizumab Maintenance Therapy in Patients With Moderately to Severely Active Ulcerative Colitis: Efficacy and Safety in the Randomised Phase 3 COMMAND Study

Abstract Background Risankizumab (RZB), a monoclonal antibody targeting interleukin-23 p19, was evaluated for maintenance therapy in patients with moderately to severely active ulcerative colitis (UC) and clinical response to RZB intravenous (IV) induction treatment in a phase 3 double-blind, placebo (PBO)-controlled withdrawal (WD) maintenance study, COMMAND (NCT03398135). Methods Patients with moderately to severely active UC who achieved a clinical response per Adapted Mayo score after 12 or 24 weeks (wks) of RZB IV treatment in the phase 2b and phase 3 INSPIRE induction studies (NCT03398148)1 were randomized 1:1:1 in COMMAND to RZB 180 mg (RZB180), 360 mg (RZB360), or PBO (RZB withdrawal) subcutaneous (SC) treatment every 8 wks for 52 wks. The efficacy analysis included responders to 12 wk of RZB IV, while the safety analysis included responders to 12 or 24 wk of RZB IV. The primary endpoint was clinical remission per Adapted Mayo score at wk 52. Key secondary endpoints included endoscopic improvement, HEMI, endoscopic remission, steroid-free clinical remission, maintenance of clinical remission, no bowel urgency, and no abdominal pain at wk 52. Results At baseline of induction, demographics and disease characteristics were similar between treatment groups; 75% of 548 patients had history of inadequate response or intolerance to ≥ 1 advanced therapy (AT). Patients receiving RZB180 (40.2%) and RZB360 (37.6%) achieved significantly higher rates of clinical remission vs WD (25.1%) (adjusted treatment difference vs WD: 16.3% and 14.2%, respectively; P ≤ .01) (Fig. 1A). Greater proportions of patients achieved endoscopic improvement, HEMI, endoscopic remission, steroid-free clinical remission, maintenance of clinical remission, no bowel urgency, and no abdominal pain with RZB180 and RZB360 vs WD (Fig. 1B). The overall rates of adverse events (AEs), and serious infections were similar among treatment groups (Table 1). Serious (presented as events/100 patient-years [E/100 PY]) (RZB180: 5.9; RZB360: 6.3; WD: 11.4) and severe AEs (RZB180: 1.6; RZB360: 4.0; WD: 8.0) were lower in the RZB arms vs WD. No active tuberculosis, adjudicated anaphylaxis, serious hypersensitivity, or adjudicated major adverse cardiovascular events were reported in any treatment group. Conclusion In patients with moderately to severely active UC responding to 12-week RZB induction therapy, RZB maintenance dosing with 180 mg and 360 mg SC was superior to placebo in achieving clinical remission as well as other key clinical, endoscopic, and histological-endoscopic endpoints. RZB was well-tolerated, with no new safety concerns observed.

P1022 One-year safety and effectiveness of ustekinumab in patients with Crohn’s disease: The K-STAR study

Abstract Background We aimed to investigate the safety and effectiveness of ustekinumab (UST) for Korean patients with Crohn’s disease (CD). Methods Adult patients with CD treated with UST were prospectively enrolled in the K-STAR (Post-MarKeting Surveillance for Crohn’s Disease patients treated with STelARa) study from April 2018 to April 2022. After single intravenous infusion of UST ~6 mg/kg, UST 90 mg subcutaneous injection was followed at week 8 and then maintenance treatment with subcutaneous UST 90 mg every 8 or 12 weeks were given, following up to week 52 to 66. Both adverse events and clinical effectiveness of UST therapy were analyzed (ClinicalTrials.gov Identifier: NCT03942120). Results Of the 464 patients enrolled from 44 medical centers across South Korea, 457 and 428 patients (Crohn’s disease activity index 150 or over) were included in the safety analysis and effectiveness analysis set, respectively (Table 1). At week 16–20 after starting UST, rates of clinical response, clinical remission and corticosteroid-free remission were 75.0% (321/428), 64.0% (274/428), and 61.9% (265/428), respectively (Figure 1A). At week 52–66, rates of clinical response, clinical remission and corticosteroid-free remission were 62.4% (267/428), 52.6% (225/428), and 50.0% (214/428), respectively (Figure 1B). Combined effectiveness (clinical response + biochemical response) was achieved in 40.0% (171/428) and 41.6% (178/428) of patients at week 16–20 and week 52–66, respectively. Bio-naïve patients exhibited significantly higher rates of combined effectiveness than bio-experienced patients (50.3% vs. 30.7% at week 16–20, p&amp;lt;0.001; 47.7% vs. 36.0% at week 52–66, p=0.014) (Figure 1A;1B). No additional benefits were observed with the concomitant use of immunomodulators. Using a multivariable analysis using backward selection, colonic involvement (vs. ileal involvement, odds ratio [OR], 0.32; 95% confidence interval [CI], 0.12–0.89; p=0.028), ileocolonic involvement (vs. ileal involvement, OR, 0.45; 95% CI, 0.23–0.89; p=0.021), baseline C-reactive protein levels (OR, 0.90; 95% CI, 0.84–0.97; p=0.009), and the exposure to two or more biologics (vs. bio-naïve, OR, 0.38; 95% CI, 0.20–0.73; p=0.003) were inversely associated with achieving clinical remission at week 52–66. Any adverse events and serious adverse events were observed in 28.2% (129/457) and in 12.7% (58/457), respectively with no new safety signal associated with UST treatment. Conclusion UST was well-tolerated, effective, and safe as induction and maintenance therapy for patients with CD in Korea. The results from this study enhance our understanding of the role of UST in managing CD patients with diverse characteristics and may help inform clinical decisions.

P851 Therapeutic drug monitoring of infliximab and adalimumab versus clinical control during maintenance therapy in patients with Inflammatory Bowel Disease

Abstract Background Although it is known that the levels of infliximab or adalimumab are correlated with clinical response, there is controversy about the best strategy to follow in patients with Inflammatory Bowel Disease (IBD) in remission and undergoing maintenance treatment. Methods We conducted a randomized, prospective, single-blinded, and multicentre trial in patients with Crohn’s Disease (CD) or Ulcerative Colitis (UC) who have remained in clinical remission for at least 12 weeks and are receiving adalimumab (ADA) or infliximab (IFX) as maintenance treatment. Patients were assigned to two groups. In the first group, patient management was done considering therapeutic drug monitoring (TDM). In the second, according to usual clinical practice (CP). The optimal serum range was within 3-7µg/ml and 5-8µg/ml for IFX and ADA respectively, based on the use of Promonitor-IFX, and Promonitor-ADL kits. The primary endpoint was to maintain patients in clinical remission (target &amp;gt;16% between both groups at 12 months) and diminish the frequency of flare-ups. Results In total, 209 patients were randomized, 29 UC (27.6%), 76 CD (72.4%) as the clinical practice group, and 24 UC (23.1%), 80 CD (76.9%) as the drug monitoring therapeutic group. Infliximab was administered in 105 patients and adalimumab in 104. Remission at the end of the study was achieved in 98.1% of the proactive dosing group and 90.5% of the clinical practice group (p=0.02), with a difference between both groups of 7.6%. The number of flare-ups was 1.3/10 patient-years in the TDM group and 2.4/10 patient-years in the CP group. The IRR of flare-up throughout the study was 0.71 (95% CI 0.32 – 1.55). In the group with IFX: IRR = 0.56 (95% CI 0.08 – 3.81) and with ADA: 0.78 (95% CI 0.29-2.16). The changes made in the drug dose are shown in Table 1. Conclusion Differences were found in favour of the TDM group, with increasing remission rates (7.6%) and half number of flare-ups. However, the pre-established effectiveness remission target (16%) was not met. In the subgroup of patients with Infliximab, management through TDM seems to have an advantage over usual clinical control.

P779 Long term efficacy of azathioprine monotherapy in patients with Inflammatory Bowel Disease

Abstract Background ECCO guidelines recommend monotherapy with azathioprine (AZA) as maintenance therapy of patients with inflammatory bowel disease (IBD) mainly in steroid-dependent disease. However, in the era of the new advanced treatments AZA is not considered as a preferable option, mainly because of the referred side effects and its use is limited in combination with biologic agents. Methods This is a retrospective observational study using data from the longitudinal, prospective IBD registry of University Hospital of Heraklion, Greece. Our aim was to study IBD patients who started on monotherapy with AZA, the profile of adverse effects they developed, the treatment persistence in monotherapy, as well as the possible related factors of treatment success [including age, gender, smoking status, body mass index, disease type, disease phenotype for Crohn’s disease (CD), history of IBD related surgery and the presence of extraintestinal manifestations]. Results Of 168 IBD patients treated with AZA, 89 (53%) were under AZA monotherapy [38 (43%) female, 67 (74%) CD, median age (IQR) 47 (32-56) years, mean (±SD) disease duration 17 (±8.4) years, median (IQR) time receiving AZA 72 (7-120) months]. Thirty (34%) patients continue their treatment till now (23 CD, 7 ulcerative colitis-UC), with a median time (IQR) of 108 (81-132) months. Of these, 18 (60%) (15 with CD and 3 with UC) present endoscopic remission and 11 (36%) (8 with CD, 3 with UC) mild endoscopic activity (based on SES-CD Score for CD and Mayo endoscopic score for UC). Of the 59 who discontinued, 33 (37%) experienced adverse events, 5 (5.5%) developed malignancy, 5 (5.5%) did not respond at baseline, 6 (6.5%) had loss of response (at a median of 91 months), 3 (3%) discontinued due to advanced age, 3 (3%) discontinued their medication on their own and 2 because of treatment de-escalation due to deep remission. Using logistic regression analysis, patients who responded to AZA monotherapy were patients without a history of IBD surgery or any extraintestinal manifestation, P=0.001 and 0.004, respectively. In the multivariate analysis, these associations remained statistically significant (P=0.01 and 0.006 respectively). Conclusion About one third of patients with IBD under AZA monotherapy experience long term response and about two thirds of them prolonged disease remission. Patients without either a history of IBD surgery or extraintestinal manifestations seem to respond better to AZA monotherapy.

P570 Efficacy and safety of Adalimumab in Very Early-onset IBD- A Multicentre Study from the Paediatric IBD Porto Group of ESPGHAN

Abstract Background Patients with very early onset inflammatory bowel disease (VEOIBD) often present with severe disease course and require escalation to biologics. Exclusion of pediatric patients from clinical trials lead to scarcity of efficacy and safety data on TNFa antagonists therapy in VEOIBD. We aimed to assess safety and efficacy of adalimumab (ADM) induction and maintenance therapy in patients with VEOIBD. Methods This was a retrospective study involving 31 sites affiliated with the IBD Porto Group and IBD Interest Group of ESPGHAN, as well as centers in North America. Demographic, clinical and laboratory data were collected from patients diagnosed with VEOIBD who commenced ADM therapy before 6 years of age between 2014 to 2023. Results We identified 77 VEOIBD patients with a median age at diagnosis of 2.6 years (interquartile range [IQR] 1.3–4.1), of whom 29 (38%) were diagnosed at age &amp;lt;2 years (infantile-onset IBD). Thirty-seven (48%) patients were diagnosed with Crohn’s disease, 25 (32%) with ulcerative colitis and 15 (20%) with IBD-unclassified. Five (9%) from those genetically tested were diagnosed with monogenic disease. Median age at initiation of ADM was 4.2 (IQR 2.8-5.1) years. Forty-four patients (57%) were Infliximab experienced, discontinued mainly due to pharmacokinetic (20 [45%]) and pharmacodynamic (13 [30%]) failures. At initiation of ADM, concomitant corticosteroids and immunomodulators were given in 37 (48%) and 29 (37%) patients, respectively. The median wPCDAI and PUCAI scores at baseline were 45 [37.5-60] and 45 [27.5-57.5], respectively. Median follow-up time was 85.4 (IQR 40.4-139.2) weeks. While patients with CD showed significant clinical improvement after 26 and 52 weeks (PCDAI decreased to 10 [0-33.4], p&amp;lt;0.001, and 10 [0-25], p&amp;lt;0.05, respectively), No significant improvement in PUCAI score was observed among patients with UC (Figure 1). Inflammatory markers and calprotectin showed a gradual decrease over time (Figure 1). Weight and Height Z scores did not differ significantly throughout the follow-up period. ADM discontinuation rates after 1 and 3 years were 40% and 65%, respectively, mainly due to primary non-response (14, 29.8%) and loss of response (19, 40.4%). Drug discontinuation rates were not dependent on concomitant immunomodulator treatment or ADM initiation or on age (less or above 3 years). Four patients (5.2%) developed severe infections, including a patient with TTC7A mutation who died following septic shock. Conclusion Adalimumab therapy was relatively safe and seemed more effective in young patients with Crohn’s disease, but not in those with ulcerative colitis. Durability was relatively low due to high rates of primary non-response and secondary loss of response.

OP14 Effect of mirikizumab on clinical and endoscopic outcomes after 1 anti-TNF failure in patients with moderately to severely active Ulcerative Colitis

Abstract Background Mirikizumab (miri), an anti-IL-23p19 antibody, has demonstrated efficacy and safety in moderately to severely active ulcerative colitis (UC) Phase 3 trials (LUCENT-1 and -2; NCT03518086, NCT03524092) among patients who had an inadequate response, loss of response, or intolerance to conventional or advanced therapy. At the LUCENT-1 induction baseline, 41% of the population had experienced a biologic/tofacitinib failure, and 36.3% experienced at least one anti-TNF failure. Among patients with one prior anti-TNF failure only, this analysis evaluated the clinical efficacy of miri compared to placebo (PBO) in induction and maintenance therapy and the efficacy of miri in extended induction. Methods In LUCENT-1, UC patients were randomized to receive 3 intravenous (IV) doses of 300mg miri or PBO every four weeks (Q4W) at W0, W4, and W8 (induction population). In LUCENT 2, responders to miri induction at W12 were re-randomized to subcutaneous (SC) 200mg miri or PBO Q4W through W52 of continuous therapy (maintenance population). Patients not achieving clinical response with miri 300mg IV at W12 received extended induction treatment with open-label 300mg miri IV at W12, W16, and W20 (extended induction population). Patients responding to extended induction at W24 entered open-label maintenance and received 200mg miri Q4W SC until W52 (extended induction responders). Endpoints evaluated were clinical response, clinical remission, symptomatic remission, endoscopic remission, corticosteroid (CS)-free remission, and histologic-endoscopic mucosal remission (HEMR). Efficacy in the subgroup of patients with failure of one anti-TNF only was assessed using Cochran-Mantel-Haenszel tests at W12 (induction population) and W52 (maintenance population). Results At LUCENT-1 baseline, of patients who experienced anti-TNF failure, 45% of patients (n=190) had one prior anti-TNF failure only (Table 1). In the induction and maintenance populations, a significantly greater proportion of miri-treated patients achieved the following efficacy endpoints compared with PBO [miri vs. PBO, p-value]: clinical response (W12: [64.4% vs. 34.1%, p=0.001]; W52: [67.2% vs. 44.8%, p=0.03]); clinical remission (W52: [44.3% vs. 17.2%, p=0.017]); symptomatic remission (W52: [63.9% vs. 34.5%, p=0.005]) (Table 2). Among the extended induction population, 45.7% achieved clinical response at W24; 75% achieved clinical response, 30% achieved clinical remission and CS-free remission at W52 (Table 2). Conclusion Mirikizumab is efficacious for induction and maintenance therapy in patients with moderately to severely active UC who have failed one prior anti-TNF.

P1074 Impact of body mass index (BMI) on clinical outcomes and drug levels in patients with Crohn’s disease receiving maintenance treatment with subcutaneous infliximab: A post hoc analysis of the LIBERTY-CD study

Abstract Background Obesity and high levels of visceral adipose tissue are associated with lower response rates to intravenous (IV) infliximab (IFX).1 Subcutaneous (SC) IFX is a novel formulation that demonstrated superiority to placebo as maintenance therapy in patients (pts) with moderate-to-severe active Crohn’s disease (CD) in the Phase 3 LIBERTY-CD study. Assessing efficacy of SC IFX by BMI is important as, unlike the IV formulation, pts receive a fixed dose. This post hoc analysis aimed to assess the association between BMI and the efficacy of SC IFX therapy. Methods Data from LIBERTY-CD (NCT03945019) were analysed; 231 pts from the SC IFX arm were divided into four subsets by their BMI: underweight (BMI &amp;lt;18.5 kg/m2, n=27); normal (18.5–24.9 kg/m2, n=133); overweight (25–29.9 kg/m2, n=53); obese (≥30 kg/m2, n=18). Co-primary endpoints at Week (W) 54 (clinical remission [CD Activity Index (CDAI) score &amp;lt;150]; endoscopic response [≥50% decrease in Simple Endoscopic Score for CD (SES-CD) from baseline (BL)]) and W54 change from BL in CDAI score were assessed by BMI subset. Correlations between BMI and CDAI score, SES-CD or median trough level of infliximab (TLI), and the impact of BMI on W54 TLI, were evaluated. Analyses were conducted in a descriptive manner. Results At W54, there were no statistically significant differences in co-primary endpoints or change from BL in CDAI score across BMI subsets, despite descending trends in rates of achieving co-primary endpoints, change in CDAI score and TLI with increasing BMI (Table). From the underweight to obese subsets, clinical remission rates were 63.0%, 66.2%, 58.5% and 44.4% (p=0.125), endoscopic response rates were 55.6%, 36.1%, 41.5% and 27.8% (p=0.207) and median changes from BL in CDAI score were −227.3, −212.9, −196.2 and −204.5 (p=0.358). No significant correlations were observed between BMI and CDAI score (Pearson r=0.0972/p=0.141; Spearman rank r=0.0619/p=0.349) or BMI and SES-CD (Pearson r=0.0446/p=0.507; Spearman rank r=0.0375/p=0.577), while there was a weak, but significant, negative correlation between BMI and TLI (Pearson r=−0.2808/p&amp;lt;0.001; Spearman rank r=−0.2829/p&amp;lt;0.001) (Figure). Additionally, there was a significant difference in median W54 TLI across BMI subsets from underweight to obese (17.0, 13.6, 9.3 and 6.6 µg/mL; p=0.007) (Table). Conclusion While there was a significant difference in TLI across BMI subsets, there was no statistically significant impact of BMI on W54 clinical or endoscopic outcomes. These results could be explained by the relatively high TLI achieved with the SC formulation. Further larger and longer-term studies including pts with morbid obesity and utilising body composition assessment are warranted. 1Yarur A et al. Gastroenterology 2023;165:963–75.

Initial efficacy evaluation of fruquintinib plus capecitabine versus capecitabine as maintenance treatment for metastatic colorectal cancer (mCRC): A randomized, controlled, phase Ib/II study.

119 Background: The standard first-line therapy followed by maintenance treatment is an optional approach to balance the efficacy and toxicity for mCRC. Fruquintinib (Fru), a highly specific inhibitor of VEGFR1/2/3, has demonstrated favorable safety and efficacy outcomes in the treatment of mCRC. In this study, we present findings from an investigation into the comparative efficacy and safety of Fru in combination with capecitabine (Cap) versus Cap as a maintenance therapy for patients (pts) with mCRC. Methods: Pts with histologically confirmed mCRC who achieved disease control (including CR/PR and SD) after at least six cycles of first-line standard chemotherapy were included in the study. During phase Ib, pts received Fru (4 mg p.o. qd, 3 weeks on/1 week off, q4w]) plus Cap (850 mg/m2, p.o. bid, d1-7 and d15-21, q4w). In phase II, pts were randomized in a 1:1 ratio to receive either Fru (RP2D, 3mg, 3 weeks on/1 week off) plus Cap or Cap alone. The primary outcome was progression-free survival (PFS). Results: By Sep 10, 2023, a total of 34 pts were enrolled in the study, and 26 pts were considered evaluable for efficacy. During Fru plus Cap (n=14) and Cap (n=12), the median age was 61.5 (39-78) and 57.5 (32-75) years. The main primary tumor side was left (64.3% / 66.7%) and approximately half of the pts harbored a RAS mutation (50.0% / 58.3%). Most pts had previously received bevacizumab therapy (57.1% /58.3%) or cetuximab (35.7% /25.0%), respectively. The mPFS was significantly improved in Fru plus Cap vs Cap (9.1 vs 3.8 months, HR: 0.289, 95% CI 0.083 to 1.01, p=0.039). Consistently, ORR (21.4% vs 0%) and DCR (92.9% vs 66.7%) were improved with Fru plus Cap. Grades 3 and 4 treatment-emergent adverse events (TEAEs) were hypertension (11.1%), oral mucositis (5.6%), voice alteration (5.6%), small intestinal obstruction (5.6%), acrodynia (5.6%) and blood bilirubin increased (5.6%) in Fru plus Cap, and diarrhea (6.3%), oral mucositis (6.3%) and acrodynia (6.3%) in Cap therapy. Conclusions: The findings suggest that Fruquintinib plus Capecitabine can be considered as a first-line maintenance therapy for metastatic colorectal cancer, as it demonstrated a promising improvement in mPFS by 5.3 months while maintaining a controlled level of safety. Clinical trial information: NCT05451719 .

The analysis of low-dose glucocorticoid maintenance therapy in patients with primary nephrotic syndrome suffering from COVID-19.

Objectives: This study aimed to describe the effects of low-dose (prednisolone acetate 2.5-7.5mg/day) glucocorticoids (GCs) maintenance therapy in patients with primary nephrotic syndrome (NS) suffering from coronavirus disease 2019 (COVID-19). Methods: A single-center retrospective study of NS patients with COVID-19 infection in Zhongda Hospital Affiliated to Southeast University from 1 February 2022 to 31 March 2023 was conducted. All enrolled patients underwent renal biopsy for the pathological diagnosis and reached complete remission (CR) or near-CR before COVID-19 infection. According to the maintained therapy regimen, patients were divided into low-dose GCs group and non-GCs group. Results: A total of 125 patients were enrolled in the study. Their median age was 46.0 ± 15.6years, and the median value of 24-h urine protein was 0.77g. The majority of these patients received treatment for more than 6months, with a significant portion achieving CR (29.6%) or near-CR (43.2%). The leading cause of NS was membranous nephropathy (52%). There were no significant differences in the baseline characteristics between low-dose GCs and non-GCs group. As compared to those in the non-GCs group, patients receiving low-dose GCs treatment showed less fatigue or muscle weakness, smell disorder, palpitations, decreased appetite, taste disorder, dizziness, sore throat or difficult to swallow and fever (p < 0.05). Moreover, patients in the low-dose GCs group were with higher median quality of life scores (85.0) than in the non-GCs group (p = 0.001). Further serum inflammatory factor analysis indicated that interleukin-6 (IL-6) levels in the non-GCs group were significantly higher than that in the low-dose GCs group (p < 0.05). Conclusion: Patients with NS in low-dose GCs maintenance therapy stage showed milder symptom, higher quality of life and decreased serum IL-6 levels compared to those, who were not on GCs maintenance therapy. These results suggest the beneficial effect of low-dose GCs therapy in NS patients with CR/near-CR suffering from COVID-19 infection.

Secondary cytoreductive surgery followed by olaparib tablets as maintenance therapy in patients with BRCA mutated recurrent ovarian cancer: A multi-center retrospective study

ObjectiveTo evaluate the effect of secondary cytoreductive surgery (SeCRS) followed by platinum-based chemotherapy (PBC) and olaparib tablets as maintenance therapy in patients with BRCA mutated recurrent epithelial ovarian cancer. MethodsThis was a retrospective study of a prospective database. We collected information on 623 patients diagnosed with BRCA mutated recurrent epithelial ovarian cancer, all of whom underwent SeCRS followed by PBC in combination with or without olaparib. Overall survival and progression-free survival were measured to evaluate treatment effectiveness. ResultsOf the 623 patients recruited, 240 underwent SeCRS plus hyperthermic intraperitoneal chemotherapy followed by PBC and olaparib maintenance therapy (Group A), 248 underwent SeCRS followed by PBC and olaparib maintenance therapy (Group B), and 135 underwent SeCRS followed by PBC only upon recurrence (Group C). The median progression-free survival for Group A was significantly longer than that for Group B (32.5 vs. 24.2 months, P<0.001), and Group B was significantly longer than Group C (24.2 vs. 15.1 months, P<0.001). The median overall survival for Groups A was significantly longer than that for Group B (71.4 vs. 63.5 months, P<0.001), and Group B was significantly longer than Group C (63.5 vs. 47.5 months, P<0.001). ConclusionsThis study suggested that SeCRS followed by PBC and olaparib maintenance therapy resulted in longer overall survival and progression-free survival than SeCRS followed by PBC only in patients with BRCA mutated recurrent ovarian cancer, especially in patients treated with SeCRS plus hyperthermic intraperitoneal chemotherapy.

Long-acting injectable antipsychotics as maintenance therapy for schizophrenia during the COVID-19 pandemic: A micro-narrative review.

The coronavirus disease pandemic has presented healthcare systems with unprecedented challenges globally and substantially impacted the management of chronic diseases such as schizophrenia. This narrative review highlights the usefulness of long-acting injectable antipsychotics (LAIs) as maintenance therapy for patients with schizophrenia during the pandemic. The analysis of relevant literature and psychiatric survey data revealed diverse trends in LAIs prescription and patient adherence with oral antipsychotics. Although some studies have reported a decrease in LAIs prescriptions owing to pandemic-related disruptions, others have suggested stable patient adherence with oral antipsychotics. Approximately 70% of Japanese psychiatrists reported an increase in schizophrenia relapse rates in a survey, underscoring the critical role of LAIs in maintaining therapeutic stability. The potential benefits of LAIs with extended dosing intervals have been highlighted, including improving oral medication adherence and reducing the frequency of hospital visits. In conclusion, this review emphasizes the continued need for uninterrupted LAIs therapy in conjunction with community and home-based care despite the disruptions caused by the coronavirus disease pandemic. Further development of LAIs maintenance therapy strategies considering the ongoing pandemic and potential future public health emergencies are required.

Batoclimab as induction and maintenance therapy in patients with myasthenia gravis: rationale and study design of a phase 3 clinical trial

IntroductionBatoclimab, a fully human monoclonal antibody that inhibits the neonatal fragment crystallisable receptor, has shown promising phase 2 clinical trial results in patients with generalised myasthenia gravis (gMG).Methods and analysisIn...

Clinical Long-Term Outcomes of Patient-Reported Outcomes in the Prospective Real-World Tofacitinib Response in Ulcerative Colitis Registry.

We previously reported the results of tofacitinib induction therapy in the prospective multisite US real-world Tofacitinib Response in Ulcerative Colitis registry. We now assessed patient-reported outcomes (PROs) and predictors of success during tofacitinib maintenance therapy. Tofacitinib Response in Ulcerative Colitis included 103 patients with refractory ulcerative colitis (UC); 67% had failed ≥ 2 biologics. Patients reported the Simple Clinical Colitis Activity Index (SCCAI), Patient-Reported Outcome Measurement Information System measures for anxiety, depression, social satisfaction, and adverse events between weeks 8 and 52 using a web-based system. Paired t test and P for trend were used to compare changes in PRO measures over time. Bivariate analyses and logistic regression models were used to determine factors associated with response (SCCAI <5) or remission (SCCAI <2) at week 52. Of 103 patients, 82.5% entered the maintenance phase and 43.7% remained on tofacitinib at week 52. Tofacitinib de-escalation to 5 mg BID occurred in 15% of patients. At week 52, 42.7% and 31.1% of all patients reported an SCCAI <5 and SCCAI ≤2, respectively. Normalization of bowel frequency, rectal bleeding, and urgency occurred in 79%, 61%, and 48% of patients remaining on maintenance therapy. Social satisfaction improved significantly ( P < 0.001), while anxiety and depression scores only numerically improved. No consistent predictors for tofacitinib long-term treatment efficacy were identified, and safety findings were consistent with the known safety profile of tofacitinib. Tofacitinib is an effective maintenance therapy in patients with refractory UC. Dose reductions infrequently occurred during maintenance. Unmet needs in UC maintenance include improvement of urgency and psychosocial factors (NCT03772145).

Efficacy and Safety of the Anti-mucosal Addressin Cell Adhesion Molecule-1 Antibody Ontamalimab in Patients with Moderate-to-Severe Ulcerative Colitis or Crohn’s Disease

Abstract Background and Aims Ontamalimab is a fully human immunoglobulin G2 monoclonal antibody against mucosal addressin cell adhesion molecule-1, developed as treatment for inflammatory bowel disease. Methods Six phase 3, multicentre, randomised, double-blind, placebo-controlled clinical trials compared efficacy and safety of ontamalimab [25 mg and 75 mg once every 4 weeks] with placebo in patients with moderate-to-severe ulcerative colitis or Crohn’s disease [two induction studies and one re-randomised maintenance study per condition]. This clinical trial programme was discontinued in 2020 for reasons unrelated to drug safety/efficacy; Crohn’s disease studies are described in the Supplementary data. Results The induction [12-week] and maintenance [52-week] studies included 659 and 366 randomised patients, respectively. More patients who received ontamalimab induction than placebo achieved the primary endpoint of clinical remission at Week 12 [25 mg, 18.5% vs 15.8%, p = 0.617, 27.0% vs 12.5%, p = 0.027; 75 mg, 29.8% vs 15.8%, p = 0.018, 29.5% vs 12.5% p = 0.014]; significantly more patients who received ontamalimab maintenance therapy than placebo achieved Week 52 clinical remission [25 mg, 53.5% vs 8.2%, p &amp;lt;0.001; 75 mg, 40.2% vs 12.8%, p &amp;lt;0.001]. Endoscopic improvement was generally significantly different vs placebo [induction: 25 mg, 27.8% vs 21.1%, p = 0.253, 35.1% vs 12.5%, p = 0.001; 75 mg, 41.1% vs 21.1%, p = 0.002, 33.9% vs 12.5%, p = 0.003; maintenance: 25 mg, 56.3% vs 9.6%, p &amp;lt;0.001; 75 mg, 48.8% vs 15.1%, p &amp;lt;0.001]. Adverse event rates were similar between ontamalimab and placebo groups. Conclusions Ontamalimab 75 mg was effective, with no safety concerns, as induction and maintenance therapy for patients with moderate-to-severe ulcerative colitis. [NCT03259334; NCT03259308; NCT03290781; NCT03559517; NCT03566823; NCT03627091]

Case report: pomalidomide as maintenance after salvage autologous stem cell transplantation in a patient with relapsed multiple myeloma

Currently, lenalidomide is the only immunomodulatory drug (IMiD) approved for maintenance therapy in patients with newly diagnosed multiple myeloma who have received high-dose chemotherapy and autologous stem cell transplantation (ASCT). The maintenance with lenalidomide showed an advantage over placebo or observation for both progression-free and overall survival in a series of phase 3 randomized trials. Salvage ASCT can be performed after disease relapse in case of a long-term response after the first transplantation or if this option has not been performed before. Pomalidomide is a third-generation IMiD approved for the treatment of relapsed and refractory multiple myeloma, which is efficient in patients with resistance to lenalidomide and proteasome inhibitors. Structurally, lenalidomide and pomalidomide are similar, and therefore the latter can also be considered as a drug for maintenance, however, there are no relevant phase 3 randomized trials. In this article, we present a clinical case of a 60-year-old patient with newly diagnosed multiple myeloma who progressed after 2 lines of induction therapy, which included lenalidomide and two proteasome inhibitors (bortezomib, ixazomib). The use of Pd combination (pomalidomide, dexamethasone) made it possible to achieve a repeated response and implement of salvage ASCT. The second ASCT was carried out only 12 months later after the first due to the COVID-19 pandemic. Subsequent long-term maintenance therapy with pomalidomide resulted in a complete response and minimal residual disease negativity. The resulting response has persisted at the time of this writing for over 2 years. To discuss the presented clinical case, the data of the French phase 2 IFM 2013-01 study were used, in which patients with failed first-line transplantation in case of relapse received PCd (pomalidomide, cyclophosphamide, dexamethasone) induction, salvage ASCT, and maintenance by Pd until disease progression. Pomalidomide may be an acceptable substitute for lenalidomide in patients with prior intolerance or refractory to this IMiD.

Rituximab as add-on therapy in patients with resistant lupus nephritis who have failed induction or maintenance therapy with other agents: A real-world experience from a single center in Mumbai.

Lupus nephritis (LN) is associated with poor outcomes and a significant risk of progression to end-stage renal disease (ESRD). Some patients with resistant LN do not respond adequately to current treatment options and need alternative strategies or therapies. The objective is to evaluate the efficacy and safety of rituximab as a re-induction therapy (Re-RTX) followed by maintenance therapy for patients with resistant LN. Twenty-four patients with resistant LN (failed initial induction therapy or severe relapse after remission) were analyzed. Re-RTX was co-administered with other immunosuppressants. The primary KDIGO criteria outcomes included renal response (complete and partial), disease progression, relapses, and infections. The median age was 28years (IQR 24.5-42), and the female-to-male ratio was 11:1. All patients had active LN, and 91.3% had proliferative LN. Baseline creatinine was 1.075mg% (IQR 0.7-1.38), and mean urine protein-to-creatinine ratio (UPCR) was 4.9 (IQR 2.8-6.65). Of the patients receiving RTX as re-induction therapy, 66.6% (16/24) had failed initial induction therapy with other immunosuppressants, whereas 33.3% (8/24) had severe relapse during maintenance therapy.Re-RTX had a favorable renal response at 6months, with 91.7% of the patients responding (20.8% complete response and 70.8% partial response). At 12months, 58.3% of the patients maintained a renal response (25% complete response and 33.3% partial response). Approximately one-third of patients relapsed within a year.Fourteen patients (58.3%) continued RTX maintenance therapy with two different treatment regimens. At 6months, Regimen-1 (500mg every 6months) resulted in a partial response in 43% (3/7) and relapse in 57% (4/7) of patients. Regimen 2 (1g dose per year) achieved a complete response in 28.5% (2/7) and a partial response in 71.5% (5/7) with no relapses at 6months.At a median follow-up of 29months, adverse renal outcomes were observed in 29.16% of the patients with progression to advanced chronic kidney disease (CKD) or end-stage renal disease (ESRD). The overall use of Re-RTX was considered safe, with a reported infection prevalence of 16%, which is comparable to the existing data. Re-RTX demonstrated efficacy and safety as an induction therapy for resistant LN. However, the response waned after 1year, underscoring the need for optimized maintenance therapy.