Normalization Of C-reactive Protein Research Articles

Accuracy and Clinical Outcomes of Fluoroscopy-Guided and Robotic-Assisted Percutaneous Pedicle Screw Fixation Performed by a Single Surgeon at a Single Center

Objective: Fluoroscopy-guided percutaneous pedicle screw fixation (FGPSF) and its further development, robot-assisted percutaneous pedicle screw fixation (RAPSF), are minimally invasive spinal surgery (MISS) techniques. FGPSF is a standard technique at our hospital, and RAPSF incorporating artificial intelligence has been performed at our hospital since October 2021. This study compared these 2 techniques and analyzed their differences, accuracy, and clinical outcomes based on our experiences.Methods: This study conducted a detailed analysis of screw accuracy and the clinical outcomes of 2 MISS techniques, FGPSF, and RAPSF. Screw accuracy was evaluated using the Gertzbein and Robbins scale, categorizing placements into grades A–E, with grades A and B considered clinically acceptable. Accuracy was assessed using postoperative computed tomography images for FGPSF and intraoperative O-arm scan images for RAPSF. Clinical outcomes were compared by examining parameters, such as hospitalization duration, C-reactive protein (CRP) normalization period, estimated blood loss (EBL), and preoperative/postoperative visual analogue scale (VAS) scores. Screw-related complications were reviewed. Independent image evaluations by nonparticipating spine specialists ensured objective and reliable assessments.Results: Both FGPSF and RAPSF demonstrated high rates of clinically acceptable screw placement, with minimal breaches that required no repositioning. The clinically acceptable rates of FGPSF and RAPSF were similar (99.17% and 99.19%, respectively). Both groups also demonstrated similar clinical outcomes. The CRP normalization period, EBL, and ΔVAS (preoperative—postoperative) scores revealed no statistically significant differences between FGPSF and RAPSF. Neither group experienced screw-related complications; however, the RAPSF group exhibited a statistically significant shorter hospital stay than the FGPSF group.Conclusion: This study compared the accuracy and clinical outcomes of FGPSF and RAPSF. Both methods demonstrated no significant differences in accuracy or clinical outcomes. Spine surgeons selected between the 2 methods based on individual patient needs, and additional research is required to fully understand the practical advantages of each technique in the clinical field.

Ustekinumab Drug Levels and Outcomes in Inflammatory Bowel Disease.

Data regarding the utility of therapeutic drug monitoring with ustekinumab (UST) are sparse. Our aim was to determine the correlation of UST levels with outcomes in a cohort of patients with inflammatory bowel disease (IBD). This was a multicenter, retrospective study of all patients with IBD who received UST from January 1, 2014 to March 1, 2022. The primary outcomes were the correlation of UST level with clinical remission (per physician global assessment), endoscopic healing [the absence of ulcers/erosions in Crohn's disease (CD) and Mayo endoscopic score ≤1 for ulcerative colitis (UC)], and normal serum C-reactive protein (CRP) (≤5mg/L). Secondary outcomes included defining optimal UST trough levels associated with favorable outcomes. A total of 71 patients (74.6% with CD; 57.7% female) were included. The median age was 39.5 years [interquartile range (IQR): 26 to 52] and 12.6% were on combination therapy with immunomodulators. Median UST trough levels were significantly higher in patients who achieved endoscopic healing at 5.4µg/mL versus 3.5µg/mL (P=0.035) and normal CRP at 5.5µg/mL versus. 3.1µg/mL (P=0.002). A cutoff UST level of 4.8µg/mL yielded the highest area under the curve (AUC) of 0.73 (95% CI: 0.61-0.80) to predict a normal CRP followed by a cutoff of 3.5µg/mL which yielded an AUC of 0.66 (95% CI: 0.52-0.81) to predict endoscopic healing. UST trough levels were significantly higher in patients who achieved a normal CRP and endoscopic healing. A cutoff UST level of 4.8µg/mL reliably predicted CRP normalization.

P890 Usefulness of subcutaneous Infliximab in patients with Inflammatory Bowel Disease in clinical practice: are increased levels associated with clinical benefit?

Abstract Background Switch from intravenous Infliximab (IFXiv) to subcutaneous Infliximab (IFXsc) in Inflammatory Bowel Disease (IBD) has been associated with an increase in trough levels. However, whether this increase is correlated with additional clinical benefit has not thus far been evaluated in clinical practice. Methods Single-center retrospective study of IBD patients who switched from IFXiv to IFXsc (for at least 3 months), between July 2021 and August 2023, due to unfavorable pharmacokinetics (IFX serum levels <3 +/- anti-IFX antibodies). Disease activity was defined as clinically: Simple Clinical Colitis Activity Index (SCCAI) ≥2 for Ulcerative Colitis (UC), Harvey Bradshaw Index (HBI) ≥5 for Crohn´s Disease (CD) or perianal fistulae with active drainage; and biochemical: C-reactive protein (CRP) >5 mg/L and/or fecal calprotectin (FC) >250 µg/g in UC and >150 µg/g in CD. Primary endpoint was to evaluate the effectiveness of IFXsc switch: achieving clinical response (decrease of SCCAI ≥2, IHB ≥3 or ≥50% in fistula drainage) or remission (SCCAI ≤1, IHB ≤4 or absence of active fistula drainage) with biomarkers normalization, or maintenance of remission, in patients with and without previous activity, respectively. Secondary endpoints were to assess IFX levels change and safety of IFXsc switch. Results Twenty-five patients (23 CD, 2 UC) were included (Table 1). Previous IFXiv therapy lasted for a median of 55 (20.6-74.1) months (100% with intensified dose and 48% with combined therapy). Median baseline IFX level was 1.7 (0.4-3) μg/mL, with anti-IFX antibodies in two cases. At baseline, 7 patients were in remission and 18 had active disease: 15/18 clinical or both clinical and biochemical (3/15 luminal, 11/15 perianal or 1/15 both), and 3/18 biochemical only. Median follow-up was 15.2 (10.2-19.2) months. After IFXsc switch, an increase of IFX level was achieved in 96% of cases, with a median final level of 12.4 μg/mL (9.2-18) (Figure 1). None of the patients in remission at the beginning relapsed during follow-up. Of patients with previous clinical activity, 66.6% achieved clinical remission (53.3%) or response (13.3%), which was seen in 50% of patients with luminal and 66.7% with perianal activity, after a median of 79 (75-210) days. CRP and FC normalization was reported in 53.3% of patients with previous biochemical activity. Treatment was discontinued only in one patient due to inefficacy. IFXsc was intensified in 8% and concomitant treatment could be withdrawn in four patients. No adverse events we reported. Conclusion Switching to IFXsc in patients with previous therapy with intensified IFXiv is not only associated with a more favorable pharmacokinetic profile but also with a greater effectiveness.

Single-center Experience With Upadacitinib for Adolescents With Refractory Inflammatory Bowel Disease.

Upadacitinib (UPA) is a novel selective JAK inhibitor approved for adults with ulcerative colitis (UC) and with positive phase 3 data for Crohn's disease (CD). Pediatric off-label use is common due to delays in pediatric approvals; real-world data on UPA are needed to understand the safety and effectiveness in pediatric IBD. This is a single-center retrospective case series study of adolescents (12-17 years) with inflammatory bowel disease IBD on UPA. The primary outcome was postinduction steroid-free clinical remission (SF-CR) defined as Pediatric UC Activity Index (PUCAI) or Pediatric CD Activity Index (PCDAI) ≤10. Secondary outcomes include postinduction clinical response (decrease ≥12.5 in PUCAI/PCDAI), postinduction C-reactive protein (CRP) normalization, 6-month SF-CR, and intestinal ultrasound response and remission. Adverse events were recorded through last follow-up. Twenty patients (9 CD, 10 UC, 1 IBD-U; 55% female; median age 15 years, 90% ≥2 biologics) were treated with UPA for ≥12 weeks (median 51 [43-63] weeks). Upadacitinib was used as monotherapy in 55% and as combination with ustekinumab and vedolizumab in 35% and 10%, respectively. Week 12 SF-CR was achieved in 75% (15/20) and 80% (16/20) with CRP normalization. About 3/4 (14/19) achieved SF-CR at 6 months. Adverse event occurred in 2 patients (10%): Cytomegaloviruscolitis requiring hospitalization and hyperlipidemia requiring no treatment. In the 75% with ultrasound monitoring, response and remission were achieved in 77% and 60%, respectively. While awaiting pediatric registration trials, our data suggest that UPA is effective in inducing and maintaining SF-CR in adolescents with highly-refractory IBD with an acceptable safety profile.

Phase 2 Study of Anakinra to Prevent CRS and Neurotoxicity after Treatment with Lisocabtagene Maraleucel: Planned Interim Analysis

BACKGROUND CD19 chimeric antigen receptor (CAR) T-cell therapies have transformed the treatment landscape for patients (pts) with relapsed/refractory B-cell malignancies, but they remain limited by significant toxicities: cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). While a more favorable toxicity profile had been reported with lisocabtagene maraleucel (liso-cel), based on our real-world experience CRS and ICANS are still observed in 70% and 30% of pts, respectively (Portuguese et al., ASH abstract #172978). Data from our group (Gazeau, TCT, 2023) and others (Strati, Blood, 2023; Park, Nat Med, 2023) suggested the recombinant interleukin-1 receptor antagonist anakinra may successfully prevent and treat CRS and ICANS. Thus, we conducted a phase 2 investigator-initiated clinical trial of anakinra to prevent CRS and ICANS after liso-cel (NCT04359784). We report here our planned interim analysis (n = 15). METHODS Adults ≥18 years of age with Karnofsky performance status ≥60% and B-cell non-Hodgkin lymphoma receiving liso-cel per the FDA label were eligible for this study. Anakinra was administered at 200 mg/day SC from day 0 through day +13 after liso-cel infusion, with the first dose administered approximately 2-4 hours prior to liso-cel infusion. CRS and ICANS severity were assessed per 2019 ASTCT criteria. The primary endpoint was the absence of any grade CRS assessed using the Bayesian optimal phase 2 design.The primary endpoint was not met if ≥6 of the first 15 pts developed any grade CRS. RESULTS Nineteen pts were screened for the study and 15 pts were enrolled. All 15 pts received liso-cel and all doses of SC anakinra. All pts were evaluable for toxicity assessment; 12 pts were evaluable for disease response assessment at day +28 (n = 3, no measurable disease prior to lymphodepletion [LD]). Pt and disease characteristics are shown in Table 1. Eleven pts (73%) had diffuse large B-cell lymphoma, 3 (20%) had active CNS involvement, and 5 (33%) had bulky disease (≥5 cm). Median pre-LD serum ferritin and C-reactive protein (CRP) were 153 ng/mL (IQR, 129-231) and 6.8 (IQR, 1.5-17.2), respectively. All 15 pts received anakinra as planned without dose adjustment or interruption. There were no injection-site reactions or AEs attributed to anakinra. Two pts developed infections during anakinra treatment and were both due to mild Clostridium difficile colitis requiring oral antibiotics. Eight pts (53%) developed any grade CRS, including 1 (7%) case of grade 3 CRS. Four pts (27%) developed any grade ICANS, including 3 (20%) with grade 3 (Figure 1). Median CRS onset and duration were 2 and 2.5 days, respectively, and median ICANS onset and duration were 6 and 9 days, respectively. Three pts (20%) required tocilizumab (range, 0-1 doses), 4 (50%) required dexamethasone (median total dose, 5 mg; range, 0-200 mg), and 1 (12%) required high-dose methylprednisolone. The best overall response rate (ORR) by Lugano criteria was 67% (complete response, n = 5 [42%]). Study pts were retrospectively compared to pts who received liso-cel per standard of care off trial without prophylactic anakinra at our center (n = 42). Despite higher median pre-LD CRP and IL-6 levels, the incidence of CRS was lower in anakinra-treated compared to anakinra-untreated pts (53% vs. 69%, respectively) with comparable median duration of CRS (2.5 vs. 3 days, respectively). The incidence and duration of ICANS were similar (27% vs. 28%; median 9 vs. 8 days, respectively), as was the incidence and duration of hospitalization (67% vs. 74%, median 9.5 vs. 10 days, respectively). Based on Locally Estimated Scatterplot Smoothing (LOESS) estimates, time from liso-cel infusion to CRP normalization was faster in patients receiving anakinra (9 days) compared to those receiving liso-cel alone (14 days). CONCLUSION Low-dose SC anakinra prophylaxis during liso-cel treatment was very well tolerated with preserved anti-tumor efficacy. While our primary endpoint was not reached at our planned interim analysis, we observed lower CRS rates and faster resolution of CRS in comparison to a real-world cohort of pts receiving liso-cel without prophylactic anakinra. To further enhance the preventative effects of anakinra, we plan to change the administration route from SC to intravenous, and to allow anakinra dose uptitration for the last 10 participants in the study.

Real-world long-term effectiveness of ustekinumab in ulcerative colitis: results from a spanish open-label cohort

Objective Ustekinumab was recently approved for the treatment of moderate-to-severe ulcerative colitis (UC). Although data from the UNIFI clinical trial are encouraging, real-world data assessing effectiveness and safety are scarce. The aim of this study was to assess the effectiveness, safety and pharmacokinetics of ustekinumab in a large cohort of refractory UC patients. Methods Multicenter observational study of UC patients who received ustekinumab for active disease. The Partial Mayo Score (PMS), endoscopic activity, C-reactive protein (CRP) and faecal calprotectin (FC) were recorded at baseline and at different time points. Demographic and clinical data, adverse events (AEs) and surgeries were documented. Results A total of 108 patients were analyzed from 4 referral Spanish hospitals. The clinical remission rates were 59%, 56.5%, 57% and 69% of patients at weeks 8, 16, 24 and 52, respectively. Normalization of FC was achieved in 39.6%, 41% and 51% at weeks 8, 24 and 52, respectively. CRP normalization was observed in 79%, 75% and 76.5% of patients at weeks 8, 24 and 52, respectively. Fewer previous anti-TNF agents and loss of response to anti-TNF were associated with clinical response and normalization of FC, respectively. AEs were observed in 5 patients, and 9 underwent colectomy. Ustekinumab persistence rates were 91%, 83% and 81% at 24, 48 and 96 weeks, respectively. Conclusions Ustekinumab demonstrated, in the real-world setting, long-term effectiveness and a favorable safety profile in a cohort of refractory UC patients.

Systemic-onset Juvenile Idiopathic Arthritis in a young child

We present a 31-month-old female child who was referred by the pediatricians with 1-year history of recurrent high-grade fever associated with polyarthritis and recurrent skin rash, which disappears within 24 hours of resolution of fever. She had lost the ability to walk unsupported because of persistent arthritis. Her Full Blood Count (FBC) was remarkable for marked leucocytosis, thrombocytosis, and a mild normocytic normochromic anemia; Erythrocyte Sedimentation Rate (ESR) and C-reactive Protein (CRP) were both elevated at 110mm/hour and 200mg/L (<7) respectively while serial blood cultures were negative for septicemia and blood films were negative for acute leukemia; HIV, hepatitis B and C virus, tuberculosis, rheumatic fever, rheumatoid arthritis, and connective tissue disease screenings were all negative. Her hemoglobin genotype is AA. She had repeatedly received treatments for malaria and ‘sepsis’ with parenteral and oral antimalarials and antibiotics with no permanent relief, hence the reason for referral to the rheumatologist. An assessment of Systemic-onset Juvenile Idiopathic Arthritis (SoJIA) was made when her serum ferritin came back elevated at 670ng/mL (4.63 – 204) and she was commenced on oral ibuprofen with remarkable improvement evidenced by resolution of fever, joint pain and rash and normalization of ESR, CRP and serum ferritin within 8 weeks of treatment. Although SoJIA is rare, it would be worthwhile to include this disease in the differential diagnoses and subsequent evaluation in any child presenting with unexplained recurrent fever associated with body rash and polyarthritis.

Vedolizumab is superior to infliximab in biologic naïve patients with ulcerative colitis

There are no prospective, head-to-head, controlled trials comparing the efficacy and safety of Infliximab (IFX) and Vedolizumab (VDZ) for the treatment of moderate-to-severe ulcerative colitis (UC), while only a few real-life retrospective studies have been published so far. We assessed the efficacy of IFX vs. VDZ in two cohorts of biologic-naïve outpatients with moderate-to-severe UC or mild, but refractory, disease. Data were extracted from patients’ files and reviewed. The duration of follow-up (FU) was 52 weeks. The primary endpoint was the clinical remission (CR) at the end of FU. Secondary endpoints were: drug persistency, time to obtain CR, clinical response at the end of the induction phase (IP), steroid-free CR (compared to patients who used steroids at baseline) at the end of FU, need for drug optimization, adverse events (AEs), and normalization of C-reactive protein (CRP). We also analyzed the causes of dropping out (primary non-response), or secondary loss of response (immunogenic or not), for each group. We enrolled 82 patients (50 IFX and 32 VDZ) who met the inclusion criteria. At the end of FU, CR was obtained in 32% of the patients on IFX and 75% on VDZ (p = 0.0003). Drug persistency was superior for VDZ compared to IFX (78% vs. 52%, p = 0.033). Clinical response at the end of induction was reached in 54% and in 81% in the IFX and VDZ group, respectively (p = 0.014). Steroid-free clinical remission at the end of FU was 62% and 94% in the IFX vs. VDZ group, respectively (p = 0.036). The need for drug optimization was higher for VDZ than for IFX (28% vs. 57%, p = 0.009), while the time to obtain CR, the incidence of AEs, mean duration of FU, and rate of CRP normalization at the end of IP were comparable between the two groups. There was a prevalence of patients dropping out because of primary non-response in IFX group (p = 0.027), while the incidence of secondary loss of response was similar in the two groups. At the multivariate analysis, CRP and Partial Mayo Score (PMS) at T0 did not correlate with CR at the end of FU in both groups. In this retrospective, real world data study in biologic-naïve patients, VDZ was superior to IFX in CR, clinical response rate at the end of IP, drug persistency, steroid-free remission, and need for optimization at the end of FU.

P570 Safety and Effectiveness of Tofacitinib in Ulcerative Colitis: Real-world Data from TOFA-UC, a SN-IBD Study

Abstract Background Real-world evidence is necessary to determine the safety and effectiveness of tofacitinib (TOFA) for the treatment of ulcerative colitis (UC) in clinical practice. Methods TOFA-UC is a multicenter observational study performed among the Sicilian Network for Inflammatory Bowel Disease (SN-IBD) on a prospectively maintained database. All consecutive patients with UC starting TOFA from its introduction in Sicily (June 2021) to June 2022 (12 months) were enrolled. The primary outcome was the assessment of safety, in terms of rate of adverse events (AEs). Secondary outcomes included the rates of clinical response, steroid-free clinical remission (based on partial Mayo score) and C-Reactive Protein (CRP) normalization after 8 weeks and at the end of follow-up, the rate of loss of response, and treatment persistence. Results 111 patients were included (mean follow-up: 31.5 ± 15.2 weeks). Only 8 patients (7.2%) were naïve to biologics, while most had previous failures to one (27.0%), two (26.1%), three (32.4%), or four (7.2%) biologics. Nineteen adverse events were reported (17.1%; incidence rate: 28.6 per 100 patient-year), including 11 cases of hypercholesterolemia, 3 infections (no cases of herpes zoster reactivation), nausea in two patients, paresthesia in one case, one colorectal cancer and one pulmonary embolism. At week 8, the rates of clinical response, steroid free clinical remission, and CRP normalization were 74.8%, 45.0%, and 56.9%, respectively, and 68.5%, 51.4%, and 65.2%, respectively, at the end of follow-up. Eighteen patients experienced a loss of response after successful induction (21.7%; incidence rate: 33.2 per 100 patient-year). The dose was increased to 10 mg bid in 15 patients, and 7 of them recaptured the response. A total of 26 patients (23.4%) discontinued TOFA over time, of whom 3 due to AEs. At multiple model regression analysis, being former smoker (hazard ratio=4.03; 95% CI=1.36-10.25; p=0.015) was the only variable associated with higher risk of treatment discontinuation. No significant differences in all outcomes of effectiveness were detected when the subgroup of patients naïve to biologics or with only one previous line of biologic therapy was compared with those with at least two previous lines of biologics. Conclusion TOFA is safe and effective in patients with UC, including those with multiple previous failures to biological therapies.

P810 Association between Ustekinumab Trough Levels, Serum IL-22 and Oncostatin M Levels with Clinical and Biochemical Outcomes in Patients With Crohn’s Disease

Abstract Background Ustekinumab is an effective treatment for patients with Crohn’s disease (CD). Strategies to monitor response to therapy may improve clinical control of the disease and reduce economical costs. Therefore, we aimed to evaluate if trough levels (TL) of ustekinumab, serum IL22 and oncostatin M levels could be considered early markers of non-response assessing their correlation with clinical and biochemical outcomes in CD. Methods We consecutively recruited patients with CD treated with ustekinumab from October 2018 to September 2020. Clinical and biochemical data were collected at baseline, at weeks 12 and 24. TL were dosed at week 12 and week 24, IL22 levels and oncostatin M serum levels were dosed at baseline and at week 12. A primary analysis determined if TL, IL22 levels and Oncostatin M serum levels were associated with clinical response (reduction in Harvey Bradshaw Index score of at least 3 points), clinical remission (Harvey Bradshaw Index score <5) and biochemical remission (negative C-reactive protein (CRP) or fecal calprotectin levels (FC) <250 μg/g). A Shapiro-Wilk test was conducted to test for normality for all variables and a Mann Whitney test was used to evaluate correlation of TL, IL22 and Oncostatin M serum levels with HBI index variation and biochemical remission. Results Among 84 patients enrolled, 10 were excluded because they were lost to follow up or had incomplete data. At week 24, 59.4% of patients had a clinical response and 47.9% were in clinical remission. TL dosed at week 12 significantly correlated with clinical response at week 12 (p=0.047) and at week 24 (p=0.019) and with clinical remission at week 12 (p=0.02) and at week 24 (p=0.02). TL at week 12 also correlated with biochemical remission both at week 12 (CRP and FC normalization, p<0.001 and p=0.04, respectively) and at week 24 (CRP and FC normalization, both p=0.01). At week 24, patients with positive FC had higher median trough concentrations of ustekinumab than those with negative FC (p=0.01). Oncostatin M levels at baseline significantly correlated with FC levels at week 12 (p<0.001) and at week 24 (p=0.04), but did not correlate with clinical remission. IL22 levels at baseline were lower in patients in clinical and biochemical remission at week 24, although these trends did not reach statistical significance (p=0.43 and p=0.86). Conclusion Ustekinumab was an effective therapy in patients with CD. TL at week 12 were predictive of both clinical and biochemical remission at week 12 and 24. Oncostatin M levels at baseline significantly correlated with FC levels at week 12 and 24.

P800 Upadacitinib is effective and safe for Crohn’s Disease: prospective real-world experience

Abstract Background Upadacitinib (upa) is a novel selective JAK-1 inhibitor that has demonstrated efficacy in the treatment of moderate to severe ulcerative colitis (UC) and Crohn’s disease (CD) and has received regulatory approval for UC. We report our prospective real-world experience with upadacitinib in patients with CD. Methods We performed a prospective analysis of clinical outcomes during upa therapy in patients with CD using pre-determined follow-up intervals at weeks 0, 2, 4, and 8 as part of a formalized treatment evaluation protocol at our institution. We used the Harvey Bradshaw Index (HBI), C-reactive protein (CRP) and fecal calprotectin (FCP). Clinically active disease was defined as HBI ≥5. Clinical response was defined as a decrease of ≥ 3 points from baseline HBI. Clinical remission was defined as HBI <5. Corticosteroid free clinical remission (CSFR) was defined as those in clinical remission, not taking any form of systemic corticosteroid at the specific time point. CRP normalization was defined as baseline elevated and then within the normal range for the lab used (Quest Diagnostics (Secaucus, NewJersey) ≤8 mg/L or University of Chicago Medicine ≤5 mg/L). FCP response and remission was assessed at three different cutoffs: less than 250 μg/g, 150 μg/g, and 50μg/g. Adverse events were recorded as treatment-related adverse events (AE) and serious adverse events (SAE). Results 47 patients with CD received ≥4 weeks of upa (Table 1). 100% had previously received anti-TNF therapy and 93.6% had received ≥2 advanced therapies (biologic, small molecule, calcineurin-inhibitor). At weeks 4 and 8, 16/21 (76.2%) and 12/16 (75.0%) achieved clinical response and 14/21 (66.7%) and 11/16 (68.8%) achieved clinical remission by 8 weeks, respectively (Table 2). Of those who were on steroids at baseline, 100% (5/5) achieved CSFR. Results were seen as early as week 2 with clinical remission rates of 52.6%. Mean HBI decreased from 6.7 (SD 4.6) at week 0 to 3.5 (3.7) at week 8 (Figure 1). Mean FCP decreased by 707.0 (SD 1026.0) μg/g at week 0 to 74.6 (SD 56.2) μg/g at week 8. Of those with FCP >150 μg/g at baseline, 100% (4/4) achieved FCP <150 μg/g by week 8 (Table 2). Mean CRP decreased by 12.8 (SD 19.1) mg/L to 4.9 (SD 8.0) mg/L at week 8. Of those with CRP >5 mg/L at week 0, 80% (4/5) achieved CRP <5 mg/L by week 8 (Table 2). 23.4% of patients had an AE after starting upa (Table 3). The most common of these was acne (14.9%). Two AEs led to discontinuation and there was a single possible SAE (anemia which was also multifactorial from severely active Crohn’s ileitis and vitamin B12 deficiency). Conclusion In this large, prospective real-world experience in medically-resistant patients with CD, we describe that upadacitinib is rapidly effective and safe.

P580 Upadacitinib is effective and safe for Ulcerative Colitis: prospective real-world experience

Abstract Background Upadacitinib (upa) is a novel selective JAK-1 inhibitor that has demonstrated efficacy in the treatment of moderate to severe ulcerative colitis (UC) and Crohn’s disease (CD) and has received regulatory approval for UC. We report a large prospective real-world experience with upa in patients with UC. Methods We performed a prospective analysis of clinical outcomes during upa therapy in patients with UC using pre-determined follow-up intervals at weeks 0, 2, 4, and 8 as part of a formalized treatment protocol. We used the Simplified Clinical Colitis Activity Index (SCCAI), C-reactive protein (CRP) and fecal calprotectin (FCP). Clinically active disease was defined as SCCAI ≥ 3. Clinical response was defined as a decrease of ≥ 3 points from baseline SCCAI. Clinical remission was defined as SCAAI < 3. Corticosteroid free clinical remission (CSFR) was defined as those in clinical remission, not taking systemic corticosteroid at the specific time point. CRP normalization was defined as baseline elevated and then within the normal range for the lab used (Quest Diagnostics (Secaucus, New Jersey) ≤8 mg/L or UChicago Medicine ≤5 mg/L). FCP response and remission was assessed at three different cutoffs: less than 250 μg/g, 150 μg/g, and 50μg/g. Adverse events were recorded as treatment-related adverse events (AE) and serious adverse events (SAE). Results 55 patients with UC received ≥4 weeks of upa (Table 1). 100% had previously received anti-TNF therapy and 81.8% had received ≥2 advanced therapies (biologic, small molecule, calcineurin-inhibitor). At 4 and 8 weeks of treatment, 18/22 (81.8%) and 19/21 (90.5%) achieved clinical response and 17/22 (77.3%) and 17/21 (81.0%) achieved clinical remission, respectively (Table 2). Of those who were on steroids at baseline, 100% (7 of 7) achieved CSFR. Results were seen as early as week 2 with clinical remission rates of 36.0%. Mean SCCAI decreased from 5.3 (SD 3.6) at week 0 to 1.71 (SD 3.96) at week 8 (p = <0.0001, Figure 1). Mean FCP decreased from 1028.5 (SD 1291) μg/g at week 0 to 530.2 (SD 715.1) μg/g (p = 0.0881). Of those with FCP >150 μg/g at baseline, 33.3% (2/6) achieved FCP <150 μg/g by week 8 (Table 2). Mean CRP (mg/L) decreased from 5.1 (SD 5.0) mg/L at week 0 to 2.5 (SD 3.3) mg/L at week 8. Of those with CRP >5 at week 0, 60% (3/5) achieved CRP <5 by week 8 (Table 2). 30.9% of patients had an AE after starting upa (Table 3). The most common of these was acne (23.6%). Two AEs led to discontinuation. There were no SAEs. Conclusion In this large prospective real-world experience in medically-resistant patients with UC, we describe that upadacitinib is rapidly effective and safe, with remission rates that exceed those seen in the pivotal trial.

P671 Ustekinumab in paediatric patients with moderately to severely active Crohn's disease: Results from the UniStar study long-term extension

Abstract Background Ustekinumab (UST) is an approved biologic for the treatment of adults with Crohn’s disease (CD). Through 16 weeks (wks), UST demonstrated high rates of efficacy, low rates of immunogenicity, and safety in paediatric patients (pts) similar to that observed in adults.1 Here, we evaluated UST in paediatric CD pts through 268 wks. Methods UniStar was a phase 1, multicentre, double-blind study in paediatric pts (2-18 years old; body weight ≥10kg) with moderately to severely active CD. Pts (n=45) were randomised 1:1 and stratified by body weight (<40kg or ≥40kg) to low (3 mg/kg [<40kg]; 130 mg [≥40kg]) or high (9 mg/kg [<40kg]; 390 mg [≥40kg]) dose intravenous UST. At wk 8, pts received 1 subcutaneous maintenance dose (2 mg/kg [<40kg]; 90 mg [≥40kg]). Pts responding to UST at wk 16 were eligible to enter the long-term extension (LTE) and continued UST maintenance dosing every 8 wks up to wk 268. This study reports efficacy, safety, pharmacokinetics (PK), and immunogenicity evaluated at wks 16, 24, 48, 224, and through 240 wks, as applicable. The primary visit was wk 48, representing outcomes after ~1 year of UST treatment. Results Of the 44 pts treated with UST, 34 (77%) responded and entered the LTE; the number of pts receiving treatment at wks 48, 104, 152, and 208 was 26 (77%), 16 (47%), 12 (35%), and 8 (24%), respectively. Among pts in the LTE (n=34), baseline median age (range) was 13.0 (6.0-17.0) years, 62% were female, 47% weighed <40kg, 18% weighed <30kg, and 94% previously failed anti-tumor necrosis factor therapy. At wk 48, 41% (14/34) of pts achieved clinical remission, and 59% (20/34) achieved clinical response. The proportion of pts with abnormal C-reactive protein (CRP) levels at baseline was 71% (24/34), and 59% (16/27) of pts achieved normalization of CRP (<3mg/L) at wk 48. By the final safety visit at wk 240, 91% of pts reported ≥1 adverse event (AE), and 15% discontinued due to AEs, with CD worsening as the most frequent reason. Infections occurred in 74% of pts, and 32% had serious AEs. The majority of serious AEs were gastrointestinal disorders associated with CD. No injection-site reactions, serious infections, malignancies, or deaths were reported. Median serum UST concentrations tended to be lower in pts weighing <40kg compared with pts weighing ≥40kg, but were generally consistent from wks 16 to 268 and remained detectable through wk 200 (Figure). Incidence of UST antibodies was low (1/34; 3%). Conclusion In the UniStar LTE, the efficacy, safety, PK, and immunogenicity of UST in paediatric pts with CD was generally consistent with adult pts for as long as 4 years of treatment. Reference: 1. Rosh JR et al. J Crohns Colitis. 2021;15(11):1931.

EFFICACY OF UPADACITINIB IN PATIENTS PREVIOUSLY TREATED WITH TOFACITINIB FOR THE MANAGEMENT OF ULCERATIVE COLITIS

Abstract BACKGROUND Tofactinib is a JAK inhibitor that targets mainly JAK 1 and JAK3 approved to treat Ulcerative Colitis (UC) in 2018. The JAK inhibitor Upadacitinib (upa) was recently approved to treat UC in March 2022 and has increased selectivity for JAK1. The relative efficacy and safety of these two JAK inhibitors is not presently clear. An important clinical question is whether patients who have not responded or lost response to tofacitinib will have a reasonable likelihood of response with upadacitinib. AIM To determine whether patients previously exposed to tofacitinib would benefit from treatment with upa. METHODS We identified adult patients at our center with active UC who had previously been treated with tofacitinib who were started on upa in the spring of 2022. Pre- and post- upa characteristics were recorded including demographic information, prior treatments, hemoglobin (hgb), albumin (alb), C-reactive protein (CRP), and partial Mayo score (pMS). Primary end points evaluated were clinical response (decrease in pMS >2), and clinical remission (pMS < 2). Secondary endpoints included serious adverse events, steroid use at time of follow up, and normalization of CRP, hgb and alb. IRB approval was obtained for the study. RESULTS A total of 3 patients were identified. All patients were given upa 45 mg daily for 8 weeks followed by 30 mg daily for maintenance. Median follow up time was 10 weeks (range 10-11 weeks). All three patients achieved the primary endpoints of clinical response and remission with pMS values of 0 at time of follow up. Patients 1 and 2 were concurrently started on a prednisone taper when initiating upa and were no longer on prednisone at time of follow up. Patients 1 and 2 had normalization of their CRP values, patient 3 only had a pre-upa CRP value available and that was 0. See table 1 for data on hgb and alb levels. Patient 1 had a pre-upa endoscopic mayo score of 3, while patients 2 and 3 had pre-upa endoscopic mayo scores of 2. No patient had post-upa endoscopic evaluation at time of follow up. No patient had any serious adverse events. CONCLUSIONS In this small case-series, use of upadacitinib in patients previously treated with tofacitinib was safe and effective in achieving clinical remission.

Efficacy of Lavage by Tube under Local Anesthesia versus Arthroscopic Treatment of Acute Septic Arthritis of Native Knee.

Although arthroscopic treatment is a minimally invasive surgery that effectively treats septic arthritis of the knee joint, it requires general or regional anesthesia. This study aimed to compare the clinical results of lavage after tube insertion versus arthroscopic treatment. Patients treated with arthroscopic treatment were included in group I (n = 76), while those treated with lavage by tube were included in group II (n = 34). We investigated the following in all patients: demographics, underlying disorders, initial serum white blood cell (WBC) count, C-reactive protein (CRP) level, synovial fluid WBC and polymorphonuclear cell counts, causative organism, initial Kellgren-Lawrence grade, lavage number, interventional delay, hospitalization days, CRP normalization time, and Western Ontario McMaster Universities Osteoarthritis index scores for clinical outcomes at 3 months postoperative. The mean interventional delay was significantly greater in group I (23.6 ± 15.6 h vs. 8.7 ± 9.3 h, p < 0.001). The lavage by tube featured a significantly shorter interventional delay time than arthroscopy, while the CRP decrease rate did not differ between groups. Moreover, lavage by tube showed no significant differences in outcomes, including laboratory results and functional outcomes at 3 months postoperative.

Adalimumab Versus Ustekinumab in Egyptian Patients with Moderate to Severe Inflammatory Bowel Disease: A Cohort Study

Inflammatory bowel disease (IBD) is a progressive, relapsing disorder. Biologics for patients with moderate-to-severe IBD have shown promising therapeutic outcomes. This research aims to compare the efficacy, safety and cost of adalimumab versus ustekinumab in a group of patients with IBD who failed treatment with infliximab. A prospective cohort study was performed on 108 patients, 53 of whom received adalimumab (Gp A) and 55 received ustekinumab (Gp U), followed up for 24 weeks. Clinical response, clinical remission and C-reactive protein (CRP) normalisation were assessed for efficacy; a cost-effectiveness analysis was conducted, and safety was evaluated. The clinical response was achieved by 86.8% of the patients in the Gp A and 92.7% of those in the Gp U group, respectively, without a significant statistical difference. The patients in the Gp A group experienced clinical remission and CRP normalisation in proportions of 47.1% and 37.3%, respectively. In contrast, the patients in the Gp U group experienced 69.8% and 58.5%, respectively, with significant statistical differences between the two groups. Adverse events were fewer in the Gp U than in the Gp A group, with a significant statistical difference. Ustekinumab was more costly than adalimumab, with a significant statistical difference between both groups. In conclusion, ustekinumab is considered more effective and safer than adalimumab in infliximab-experienced patients but with a higher cost in patients with moderate to severe IBD.

Effect of Molnupiravir on Biomarkers, Respiratory Interventions, and Medical Services in COVID-19 : A Randomized, Placebo-Controlled Trial.

In the MOVe-OUT trial, molnupiravir showed a clinically meaningful reduction in the risk for hospitalization or death in adults with mild to moderate COVID-19 and risk factors for progression to severe disease. To identify other potential clinical benefits of molnupiravir versus placebo. Secondary analysis of the randomized, double-blind, placebo-controlled phase 3 component of MOVe-OUT. (ClinicalTrials.gov: NCT04575597). 107 sites globally. 1433 nonhospitalized adults aged 18 years or older with mild to moderate COVID-19. Molnupiravir, 800 mg, or placebo every 12 hours for 5 days. Changes from baseline in C-reactive protein (CRP) concentration and oxygen saturation (Spo 2), need for respiratory interventions (including invasive mechanical ventilation), and need for medical services in all randomly assigned participants through day 29, and need for respiratory interventions and time to discharge in the subgroup of participants who were hospitalized after randomization. Participants receiving molnupiravir showed faster normalization of CRP and Spo 2, with improvements observed on day 3 of therapy, compared with placebo. Molnupiravir-treated participants had a decreased need for respiratory interventions versus placebo-treated participants (relative risk reduction [RRR], 34.3% [95% CI, 4.3% to 54.9%]), with similar findings in participants who were hospitalized after randomization (RRR, 21.3% [CI, 0.2% to 38.0%]). Hospitalized participants who received molnupiravir were discharged a median of 3 days before those who received placebo. Acute care visits (7.2% vs. 10.6%; RRR, 32.1% [CI, 4.4% to 51.7%]) and COVID-19-related acute care visits (6.6% vs. 10.0%; RRR, 33.8% [CI, 5.6% to 53.6%]) were less frequent in molnupiravir- versus placebo-treated participants. Some analyses were performed post hoc. Longer-term benefits of molnupiravir therapy were not evaluated. Participants were not immunized against SARS-CoV-2. The findings suggest there are additional important clinical benefits of molnupiravir beyond reduction in hospitalization or death. Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc.

Serial evaluation of thoracic radiographs and acute phase proteins in dogs with pneumonia.

BackgroundAcute phase proteins (APP) may guide treatment of pneumonia in dogs but correlations with radiographic abnormalities are poorly characterized.ObjectivesDevelop a thoracic radiographic severity scoring system (TRSS), assess correlation of radiographic changes with APP concentrations, and compare time to APP and radiograph normalization with duration of antimicrobials treatment.AnimalsSixteen client‐owned dogs, 12 with aspiration pneumonia, and 4 with community‐acquired pneumonia.MethodsConcentrations of C‐reactive protein (CRP), serum amyloid A (SAA), and haptoglobin were measured on days 1, 3, 7, 14, 28, and 60 and orthogonal 2‐view thoracic radiographs were obtained on days 1, 7, 14, 28, and 60. Treatment was clinician‐guided and blinded to APP concentrations. Radiographic severity scores were assigned by blinded, randomized retrospective review by 2 board‐certified radiologists with arbitration by a third radiologist.ResultsMedian (interquartile range [IQR]) time to normalization of CRP (7 days [7‐14]) and SAA concentrations (7 days [7‐14]) were shorter than antimicrobial treatment duration (17.5 days [14.5‐33.5]; P = .001 and .002, respectively) and TRSS normalization (14 days [8.8‐52], P = .02 and .02, respectively). The CRP and SAA concentrations were positively correlated with TRSS (CRP r s , 0.643; SAA r s , 0.634; both P < .0001). Both CRP and SAA identified normal thoracic radiographs area under the curve (AUC) 0.873 and 0.817, respectively, both P < .0001. Interobserver agreement for TRSS assignment was moderate (κ, .499; P < .0001).Conclusion and Clinical ImportanceConcentrations of CRP and SAA normalized before radiographic resolution and before clinicians discontinued antimicrobial treatment. The CRP and SAA concentrations may guide duration of antimicrobial treatment for dogs with pneumonia.

Antimicrobial discontinuation in dogs with acute aspiration pneumonia based on clinical improvement and normalization of C-reactive protein concentration.

BackgroundEvidence regarding optimal treatment duration in dogs with aspiration pneumonia (AP) and the role of thoracic radiographs (TXR) and lung ultrasonography (LUS) in the long‐term follow‐up of affected dogs is lacking. C‐reactive protein (CRP) is a reliable acute phase protein to monitor bacterial pneumonia in dogs.HypothesisInvestigate the safety of antimicrobial discontinuation based on clinical improvement and serum CRP normalization, as well as the usefulness of TXR and LUS for follow‐up.AnimalsDogs diagnosed with AP and treated with antimicrobials.MethodsProspective observational study. Antimicrobials were discontinued based on clinical improvement and serum CRP normalization after 1, 3, or 5 weeks. At each consultation, a quality‐of‐life questionnaire, physical examination, serum CRP, TXR, and LUS were assessed. Short‐ (2 weeks) and long‐term (>1 month) follow‐ups after treatment discontinuation were performed to monitor for possible relapses.ResultsSeventeen dogs were included. Antimicrobials were discontinued after 1 week in 12 dogs (70.6%) and 3 weeks in the remaining 5 dogs (29.4%). Short‐term relapse was not observed in any dog and long‐term relapse was diagnosed in 3 dogs. Thoracic radiographs and LUS were useful for diagnosis, but did not add additional information during follow‐up, because image normalization lagged behind clinical improvement and serum CRP normalization.Conclusion and Clinical ImportanceDogs with AP can be safely and effectively treated using a short‐term antimicrobial regimen discontinued after clinical improvement and serum CRP normalization. Imaging might still be useful for complicated cases with a less favorable response to treatment.

Comparison of lung ultrasound, chest radiographs, C-reactive protein, and clinical findings in dogs treated for aspiration pneumonia.

BackgroundComparison of clinical findings, chest radiographs (CXR), lung ultrasound (LUS) findings, and C‐reactive protein (CRP) concentrations at admission and serial follow‐up in dogs with aspiration pneumonia (AP) is lacking.HypothesisLung ultrasound lesions in dogs with AP are similar to those described in humans with community‐acquired pneumonia (comAP); the severity of CXR and LUS lesions are similar; normalization of CRP concentration precedes resolution of imaging abnormalities and more closely reflects the clinical improvement of dogs.AnimalsSeventeen dogs with AP.MethodsProspective observational study. Clinical examination, CXR, LUS, and CRP measurements performed at admission (n = 17), 2 weeks (n = 13), and 1 month after diagnosis (n = 6). All dogs received antimicrobial therapy. Lung ultrasound and CXR canine aspiration scoring systems used to compare abnormalities.ResultsB‐lines and shred signs with or without bronchograms were identified on LUS in 14 of 17 and 16 of 17, at admission. Chest radiographs and LUS scores differed significantly using both canine AP scoring systems at each time point (18 regions per dog, P < .001). Clinical and CRP normalization occurred in all dogs during follow up. Shred signs disappeared on LUS in all but 1 of 6 dogs at 1 month follow‐up, while B‐lines and CXR abnormalities persisted in 4 of 6 and all dogs, respectively.Conclusion and Clinical ImportanceLung ultrasound findings resemble those of humans with comAP and differ from CXR findings. Shred signs and high CRP concentrations better reflect clinical findings during serial evaluation of dogs.