ABSTRACT
Introduction: Guselkumab (GUS), an IL-23p19 antagonist, had greater efficacy than placebo (PBO) in achieving clinical response and clinical remission atWeek (Wk) 12 in the randomized, controlled Phase 2b QUASAR Induction Study 1 (NCT04033445) in patients with moderately to severely active ulcerative colitis (UC).1 Patients who were not in clinical response at Wk 12 received GUS treatment through Wk 24. Here, we report GUS cumulative efficacy and safety results for Induction Study 1. Method(s): Eligible patients had moderately to severely active UC (modified Mayo score of 5 to 9 with a Mayo endoscopy subscore >=2) at baseline. Patients were randomized 1:1:1 to IV GUS 200mg, 400mg, or PBO at Wks 0, 4, and 8. Patients who were not in clinical response to IV induction at Wk 12 received GUS treatment (PBO IV->GUS 200mg IV;GUS 200mg IV->GUS 200mg SC;GUS 400mg IV->GUS 200mg SC) at Wks 12, 16, and 20 and were evaluated at Wk 24 (Figure). Matching IV or SC PBO was administered to maintain the blind. Result(s): Three hundred thirteen patients were randomized and treated at baseline. Demographic and disease characteristics at baseline were similar among the treatment groups, and approximately 50% had a prior inadequate response or intolerance to advanced UC therapy. AtWk 12, clinical response was achieved by 61.4% (62/101) and 60.7% (65/107) of patients randomized to GUS 200mg and GUS 400mg IV vs 27.6 % (29/105) of patients randomized to PBO IV (both p< 0.001). Of the patients in the GUS groups who were not in clinical response at Wk 12, 54.3% (19/35) in the GUS 200mg IV->200mg SC group and 50.0% (19/38) in the GUS 400mg IV->200mg SC group achieved clinical response at Wk 24. Clinical response atWk 12 or 24 was achieved by 80.2% of patients who were randomized to GUS 200mg IV and 78.5% of patients who were randomized to GUS 400mg IV. For patients who received PBO IV->GUS 200mg IV, clinical response at Wk 24 (65.2%) was similar toWk 12 clinical response following GUS 200mg IV induction (61.4%). The most frequent adverse events among all GUS-treated pts (n=274) were anemia (7.7%), headache (5.1%), worsening UC (4.4%), COVID-19 (3.6%), arthralgia (2.9%) and abdominal pain (2.6%) which are consistent with Wk 12 results. Conclusion(s): Overall, approximately 80% of patients randomized to receive GUS achieved clinical response at Wk 12 or 24. Continued treatment with SC GUS allowed 50-54.3% of IV GUS Wk 12 clinical nonresponders to achieve clinical response at Wk 24. No new safety concerns for GUS were identified. (Figure Presented).
ABSTRACT
Background: Guselkumab (GUS), an IL-23p19 antagonist, had greater efficacy than placebo (PBO) in achieving clinical response and clinical remission at Week (Wk) 12 in the randomized, controlled Phase 2b QUASAR Induction Study 1 (NCT04033445) in patients with moderately to severely active ulcerative colitis (UC).1 Patients who were not in clinical response at Wk 12 received GUS treatment through Wk 24. Here, we report GUS cumulative efficacy and safety results for Induction Study 1. Method(s): Eligible patients had moderately to severely active UC (modified Mayo score of 5 to 9 with a Mayo endoscopy subscore >=2) at baseline. Patients were randomized 1:1:1 to IV GUS 200mg, 400mg, or PBO at Wks 0, 4, and 8. Patients who were not in clinical response to IV induction at Wk 12 received GUS treatment (PBO IVGUS 200mg IV;GUS 200mg IV->GUS 200mg SC;GUS 400mg IV->GUS 200mg SC) at Wks 12, 16, and 20 and were evaluated at Wk 24 (Figure 1). Matching IV or SC PBO was administered to maintain the blind. Result(s): Three hundred thirteen patients were randomized and treated at baseline. Demographic and disease characteristics at baseline were similar among the treatment groups, and approximately 50% had a prior inadequate response or intolerance to advanced UC therapy. At Wk 12, clinical response was achieved by 61.4% (62/101) and 60.7% (65/107) of patients randomized to GUS 200mg and GUS 400mg IV vs 27.6% (29/105) of patients randomized to PBO IV (both p<0.001). Of the patients in the GUS groups who were not in clinical response at Wk 12, 54.3% (19/35) in the GUS 200mg IV->200mg SC group and 50.0% (19/38) in the GUS 400mg IV->200mg SC group achieved clinical response at Wk 24. Clinical response at Wk 12 or 24 was achieved by 80.2% of patients who were randomized to GUS 200mg IV and 78.5% of patients who were randomized to GUS 400mg IV. For patients who received PBO IV->GUS 200mg IV, clinical response at Wk 24 (65.2%) was similar to Wk 12 clinical response following GUS 200mg IV induction (61.4%). The most frequent adverse events among all GUS-treated pts (n=274) were anemia (7.7%), headache (5.1%), worsening UC (4.4%), COVID-19 (3.6%), arthralgia (2.9%) and abdominal pain (2.6%) which are consistent with Wk 12 results. Conclusion(s): Overall, approximately 80% of patients randomized to receive GUS achieved clinical response at Wk 12 or 24. Continued treatment with SC GUS allowed 50-54.3% of IV GUS Wk 12 clinical nonresponders to achieve clinical response at Wk 24. No new safety concerns for GUS were identified.
ABSTRACT
Background: To our knowledge, no published work has described precisely the severity and evolution of SARS-CoV-2 infection in patients with spondyloarthritis (SpA). Data on COVID-19 from cohorts of patients with immune-mediated infam-matory diseases concern small samples of SpA. Objectives: Our objective was to describe the severity and course of COVID-19 in a large cohort of patients with SpA, including axial SpA (axSpA) and psoriatic arthritis (PsA), and to identify factors associated with severe forms. Methods: Patients: individuals with Spondyloarthritis (SpA) from the French RMD COVID-19 cohort (observational, national, multicenter cohort) with a diagnosis of COVID-19 (clinical, PCR, CT or serology) were included. Data collected: demographics, type of SpA, comorbidities, treatments, severity of COVID-19. Severity of COVID-19 was graded according to care needed: mild = outpatient care;moderate = non-intensive hospital treatment;severe = intensive care unit admission or death;severe = moderate or severe. Statistical analyses: Logistic regression models were used to identify factors associated with these severe forms. All variables with p <0.20 in the univariate analysis were proposed in the multivariate model. Treatment variables (non-ste-roidal anti-infammatory drugs (NSAIDs), methotrexate (MTX), sulfasalazine (SLZ), TNF inhibitors (TNFi), IL-17 inhibitors (IL-17i) and IL-23p19/p40 inhibitors (IL-23p19/p40i)) were included in the models, even if p≥0.20. Results: Between March 2020 and April 2021, 626 SpAs reported COVID-19 with a mild course in 508 cases (81.1%), moderate in 93 cases (14.8%), and severe in 25 cases (3.9%), including 6 deaths. The cohort analyzed included 349 women (55.8%), mean age 49.3 ± 14.1 years, mean BMI 27.1 ± 5.4 with 403 axSpA (64.4%), 187 PsA (29.9%) and 36 other SpA, duration of disease 11.3 ± 9.8 years;352 (56.2%) had at least one comorbidity, of which obesity (23.6%), hypertension (15.5%), and smoking (10.4%) were the most frequent. Among them, 104 were treated with NSAIDs (16.6%), 186 with conventional synthetic disease-modifying antirheumatic drugs (DMARDs) including 156 MTX, and 460 (73.5%) with biological DMARDs (379 TNFi, 57 IL-17i, 15 IL-23p19/p40i, 9 others). The following variables were associated with severe COVID-19 outcomes: age, body mass index, chronic obstructive lung disease, cardiovascular disease, diabetes, hypertension, interstitial lung disease, renal failure, and corticosteroids intake. The factors independently associated with severe COVID-19 outcomes were cor-ticosteroid intake (3.15 [CI95%: 1.46-6.76], p 0.004), and age (OR=1.06 [CI95%: 1.04-1.08], p <0.001] while anti-TNF (OR=0.26 [CI95%: 0.09-0.78], p=0.01]) was protective. NSAIDs intake (OR=0.97 [CI95%: 0.48-1.98]), SLZ (OR=7.9 [CI95%: 0.60-103]), or anti-IL17 (OR=0.37 [CI95%: 0.10-1.31]) was not associated with infection severity. Conclusion: The course of COVID-19 was mild for the majority of SpA patients (81.1%). Corticosteroid intake was associated with more severe COVID-19 outcomes, whereas TNFi were found to be protective.