Long-term therapeutic options providing durable response and tolerability are needed for psoriatic arthritis (PsA). The ongoing KEEPsAKE 2 trial is evaluating risankizumab treatment in patients with active PsA who previously had inadequate response/intolerance to ≥ 1 conventional synthetic disease-modifying antirheumatic drug (csDMARD-IR) and/or 1–2 biologic DMARDs (bDMARD-IR). Herein, we report results through 100 weeks of treatment. KEEPsAKE 2 is a global phase 3 trial. Patients with active PsA were randomized 1:1 to double-blind subcutaneous risankizumab 150 mg or placebo (weeks 0, 4, and 16). At week 24, all patients received open-label risankizumab every 12 weeks until end of study. Efficacy endpoints included achieving ≥ 20% improvement in PsA symptoms using American College of Rheumatology criteria (ACR20), attaining minimal disease activity (MDA; meeting ≥ 5/7 criteria of low disease activity and extent), and improving in other measures. At the cutoff date, 345/443 (77.9%) patients were ongoing in the study. ACR20 was achieved in 57.1% and 52.5% of the continuous risankizumab and placebo/risankizumab cohorts, respectively, at week 100 and in 60.0% and 55.8%, respectively, at week 52. In week 52 responders, maintenance of ACR20 at week 100 was achieved in 74.8% (continuous risankizumab) and 78.7% (placebo/risankizumab) of patients. In the continuous risankizumab and placebo/risankizumab cohorts, respectively, MDA was achieved by 33.0% and 33.3% of patients at week 100 and by 27.2% and 33.8% at week 52. Among MDA responders at week 52, maintenance of MDA response was achieved by 83.6% and 73.0% of the continuous risankizumab and placebo/risankizumab cohorts, respectively. Risankizumab was well tolerated through week 100. Risankizumab demonstrated durable efficacy and tolerability through 100 weeks; most patients who achieved ACR20 and MDA responses at week 52 maintained this achievement through week 100. There were no new safety signals in patients who had csDMARD-IR and bDMARD-IR. ClinicalTrials.gov NCT03671148. Risankizumab, a biologic disease-modifying antirheumatic drug, helps control the body's immune system to reduce symptoms of psoriatic arthritis (a disease that inflames the joints of people who have the skin condition psoriasis). The ongoing KEEPsAKE 2 study is evaluating how well risankizumab works and how safe it is for treating adult patients with active psoriatic arthritis who previously experienced inadequate response to one or more specific types of disease-modifying anti-arthritis drugs. Patients were randomly assigned to receive either risankizumab or an inactive drug; after 24 weeks, all patients received risankizumab. At study week 100, 57% of patients who were assigned to receive continuous risankizumab since the start of the study experienced a 20% or more improvement in a measure of psoriatic arthritis symptoms using criteria established by the American College of Rheumatology (ACR20); a similar proportion of patients achieved a 20% improvement at both weeks 24 and 52. Similarly, 56% and 53% of patients who switched from inactive drug to risankizumab achieved ACR20 at weeks 52 and 100 (more than before switching to risankizumab at week 24). Minimal disease activity (MDA) was evaluated by assessing joint and skin symptoms, affected body surface area, pain, and physical function. At week 100, 33% of patients achieved MDA (both groups), which was similar to week 52. Most patients who achieved ACR20 or MDA at week 52 maintained responses at week 100. Improvements with risankizumab were seen in several other measures of treatment outcomes through week 100. Risankizumab was generally safe through 100 weeks.
Introduction: We evaluate safety and efficacy of risankizumab (RZB) vs. placebo (PBO) in adult patients with moderate-to-severe non-pustular palmoplantar psoriasis (PPPsO).
Method: IMMprint, a Ph3b study evaluated safety and efficacy of RZB vs. PBO in moderate-to-severe PPPsO patients with a static physician’s global assessment(sPGA) of moderate or severe ≥3, palmoplantar psoriasis area and severity index(PPASI) ≥8 and at least 1 additional PsO plaque. The 52-week treatment was split into period A, patients randomized (1:1) to RZB 150-mg or PBO, and period B, patients continuing RZB or switching from PBO to RZB (PBO/RZB). Primary endpoint was achievement of palmoplantar investigator’s global assessment (ppIGA) 0/1 with at least 2-point reduction from baseline at Wk16. Ranked secondary endpoints include ≥75% & 90% improvement in PPASI (PPASI75, PPASI90), sPGA 0/1 and 100% improvement in PPASI(PPASI100) at Wk16.
Results: Of 174 enrolled, 87(mean age[SD]: 56.9[12.9] years) were randomized to RZB and 87(mean age[SD]: 53.9[14.3] years) were randomized to PBO. Baseline characteristics were similar except for numerical difference in PsA (RZB vs. PBO: 11.5% vs 4.6%, respectively). At Wk16, a significantly higher proportion receiving RZB achieved ppIGA 0/1 than PBO(33.3% vs. 16.1%, p = 0.006). Patients receiving RZB also demonstrated significantly higher responses than patients receiving PBO in all ranked secondary endpoints: PPASI75 (42.5% vs 14.9%, P < 0.001); PPASI90 (27.6% vs 5.7%, p<0.001); sPGA 0/1 (32.2% vs 11.5%, p < 0.001); and PPASI100 (17.2% vs. 1.1%, p < 0.001). Four patients (3 RZB: 1 PBO) discontinued drug in period A. At Wk52, ppIGA 0/1 was achieved by 50.6% of RZB patients and 61.7% of PBO/RZB group. Proportion of patients achieving PPASI75 at Wk52 was 57.5%(RZB) vs. 65.4% (PBO/RZB). Achievement of sPGA 0/1 (%RZB vs. %PBO/RZB) was 43.7% vs. 66.7%; PPASI100 was achieved by 26.4% (RZB) and 37.0% (PBO/RZB) patients at Wk52. Proportion of patients with adverse events were 29.1%(RZB) and 23.0%(PBO) in period A, and 49.4%(RZB) and 35.8% (PBO/RZB) in period B. One RZB patient with prior cardiovascular risk factors had an adjudicated myocardial infarction and subsequently died after 140-day follow-up period. The number of patients with COVID-19 were 3 (RZB; 1 serious infection) and 2(PBO) in period A and 11 (RZB) and 7 (PBO/RZB) in period B.
Conclusion: This study demonstrates RZB can provide effective improvement compared to PBO by Wk16 with continuous improvement until Wk52 with no new safety signals in patients with moderate-to-severe PPPsO.
Introduction
The IMMpulse study (NCT04908475) demonstrated superior efficacy of risankizumab (RZB) compared to apremilast (APR) in systemic-eligible patients with moderate plaque psoriasis (PsO).
Material and Methods
This phase 4, multi-center, randomized, open-label, assessor-blinded, active comparator study compared RZB to APR in adult systemic-eligible patients with moderate plaque PsO. In period A, patients were randomized 1:2 to receive RZB (150 mg) or APR (30 mg twice daily) for 16 weeks. In period B, all APR-treated patients were re-randomized 1:1 to RZB or APR stratified by their ≥ 75% improvement in psoriasis area and severity index (PASI75) response. All RZB patients in period A continued treatment till week 52. Pre-specified efficacy endpoints included change in PASI and body surface area (BSA) from baseline. Continuous endpoints were assessed using mixed-effect model repeat measures to handle missing data.
Results
Baseline characteristics were similar between the treatment arms. At week 16, PASI75 was achieved by 84.7% (RZB-treated) and 18.8% (APR-treated) patients. Mean PASI improved from 14.6 at baseline to 1.7 (RZB-treated), and from 14.5 at baseline to 8.8 (APR-treated) patients. Mean BSA improved from 13.1% to 2.6% with RZB, and from 13.1% to 10.6% for APR-treated patients. APR-treated patients not achieving PASI75 at week 16 who switched to RZB achieved a mean PASI of 0.7 at week 52, compared to 3.1 at week 52 in patients who continued with APR. In these same patients, those that switched to RZB achieved a mean BSA of 1.4% at week 52 compared to 6.3% for patients who continued APR. Most frequently observed treatment emergent adverse events were COVID-19 and nasopharyngitis for RZB, and diarrhea, nausea, and headache for APR.
Conclusions
These results demonstrate minimal residual disease observed with continuous RZB treatment and support the opportunity to elevate treatment outcomes with RZB in systemic-eligible patients with moderate plaque PsO.
e23580 Background: Pexidartinib, a kinase inhibitor, is approved for treatment of adult patients with symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations and not amenable to improvement with surgery. Due to risk of serious and potentially fatal liver injury, pexidartinib is available via a Risk Evaluation and Mitigation Strategy (REMS) Program. A requirement of the REMS is to conduct a qualitative evaluation of stakeholder Knowledge, Attitudes, and Behavior (KAB) of risks via surveys. The objective of the qualitative evaluation is to review key risk message questions with respect to understanding, relevance, clarity and provide recommendations on alternative language, phrasing, and structure. Methods: Anonymized, one-on-one 45–60-min phone interviews with patients and HCPs were conducted by UBC. Patients ≥18 y, diagnosed with TGCT (prioritized) or metastasis/sarcoma of the connective tissue, with different levels of education and fluent reading/speaking English were included. To participate, HCPs were required to treat patients with TGCT (prioritized) or metastasis/sarcoma of the connective tissue, treat patients ≥75% of their time, and clearly read/speak English. Participants were required to complete an Interview Release Form (IRF) and confirm access to a computer/tablet. Participants had little/no familiarity with pexidartinib materials. All interviews followed a standard process, used a pre-scripted guide on general instructions, confidentiality, safety event reporting, rapport building and assessment of health literacy (patients only). Feedback regarding understanding, relevance, and clarity were used to recommend potential alternate language/phrasing. To receive compensation participants were required to execute/return the IRF. Results: Twelve patients were interviewed, majority 67% had TGCT; mean age 52 y; 58% female; 42% reported some college/associates degree. 12 HCPs were interviewed, 67% treated patients with TGCT; 100% male; mean years practicing 22; all spent 75% or more time seeing patients; primary specialty Orthopedics. Areas of confusion/misunderstanding were reported, and questions were then revised. Patient findings: complexity and wordiness; HCP findings: repetition/difficulty reading, and some terminology was not self-explanatory. Conclusions: Feedback from HCPs and patients was received to improve the key risk messages of the KAB. Qualitative research is recommended to improve comprehension and data quality collected.
Risankizumab has demonstrated superior efficacy compared to other psoriasis treatments, including secukinumab, adalimumab, and ustekinumab; switching to risankizumab from other psoriasis treatments has shown superior clinical and quality of life (QoL) outcomes. We evaluated the efficacy and safety of directly switching patients with moderate-to-severe plaque psoriasis and a suboptimal response to interleukin (IL)-17 inhibitors (secukinumab or ixekizumab) to risankizumab. This 52-week, phase 3b study enrolled patients (≥ 18 years) with moderate-to-severe plaque psoriasis who had previously been treated with the recommended dose of secukinumab or ixekizumab for ≥ 6 months but did not achieve an optimal response (static Physician's Global Assessment [sPGA] 2/3; body surface are [BSA] 3– < 10%). Patients received subcutaneous risankizumab (150 mg) without washout. The primary endpoint was the proportion of patients achieving sPGA of 0/1 at week 16. Secondary endpoints included sPGA 0/1 at week 52, sPGA 0, Dermatology Life Quality Index (DLQI) 0/1, and Psoriasis Symptoms Scale (PSS) 0 at weeks 16 and 52. Safety was monitored throughout the study. The study included 244 patients. sPGA 0/1 was achieved by 57.4% and 62.3% at week 16 and 52. At week 16, sPGA 0, DLQI 0/1, and PSS 0 were achieved by 20.5%, 40.2%, and 20.9%, respectively. At week 52, these proportions increased to 27.1% for sPGA 0, 47.2% for DLQI 0/1, and 27.5% for PSS 0. Most frequently reported adverse events (reported in ≥ 5% of patients) in risankizumab-treated patients were COVID-19 infection (8.6%) and nasopharyngitis (5.7%). No new safety signals were observed. Directly switching to risankizumab improved outcomes and QoL in patients with moderate-to-severe psoriasis who had suboptimal responses to anti-IL-17 inhibitors (secukinumab or ixekizumab). The safety results are consistent with previously reported safety of risankizumab. This study supports the efficacy of risankizumab in patients previously treated with biologics, including IL-17 inhibitors, and suggests a direct switch to risankizumab for improved clinical outcomes and QoL. ClinicalTrials.gov identifier: NCT04102007.
Patients with psoriatic arthritis (PsA) require treatment providing durable long-term efficacy in different disease domains as well as safety. We present 100-week efficacy and safety results of risankizumab in patients with active PsA and previous inadequate response/intolerance to ≥ 1 conventional synthetic disease-modifying antirheumatic drug (csDMARD-IR). KEEPsAKE 1 (NCT03675308) is a global phase 3 study, including a 24-week, double-blind, placebo-controlled and ongoing open-label extension periods. Patients were randomized 1:1 to receive risankizumab 150 mg or placebo at baseline and weeks 4 and 16. After week 24, all patients received open-label risankizumab every 12 weeks thereafter. Patients were evaluated through 100 weeks. Endpoints included achieving ≥ 20% reduction in American College of Rheumatology criteria for symptoms of rheumatoid arthritis (ACR20), minimal disease activity (MDA; defined as ≥ 5/7 criteria of low disease activity and extent), and other measures. Overall, 828/964 (85.9%) patients completed week 100. For patients receiving continuous risankizumab, 57.3%, 70.6%, and 64.3% achieved ACR20 at weeks 24, 52, and 100, respectively. For the placebo/risankizumab cohort, 33.5% achieved ACR20 at week 24 but increased after switching to active treatment at weeks 52 (63.7%) and 100 (62.1%). In ACR20 responders at week 52, 81.2% of both treatment cohorts maintained response at week 100. MDA was achieved by 25.0%, 38.3%, and 38.2% of the continuous risankizumab cohort at weeks 24, 52, and 100. In the placebo/risankizumab cohort, 10.2% achieved MDA at week 24, increasing at weeks 52 (28.0%) and 100 (35.2%). MDA response was maintained at week 100 in week 52 responders in the continuous risankizumab (75.5%) and placebo/risankizumab cohorts (78.2%). Similar trends were observed for other efficacy measures. Risankizumab was generally well tolerated through 100 weeks. For patients with active PsA who are csDMARD-IR, risankizumab demonstrated durable long-term efficacy and was generally well tolerated, with a consistent long-term safety profile. ClinicalTrials.gov identifier, NCT03675308. Psoriatic arthritis (PsA) often affects individuals with the skin condition psoriasis. A biologic disease-modifying antirheumatic drug can help control inflammation and regulate the immune system to ease symptoms and slow progression of PsA. The ongoing KEEPsAKE 1 study is evaluating the efficacy and safety of risankizumab in patients with active PsA who previously have not had success with ≥ 1 conventional disease-modifying antirheumatic drug. Patients were initially treated with risankizumab 150 mg (continuous risankizumab group) or inactive drug (inactive drug/risankizumab group). After 24 weeks, all received risankizumab for the rest of the study. At week 100, 64% (continuous risankizumab group) and 62% (inactive drug/risankizumab group) of patients had ≥ 20% improvement in PsA symptoms (measured using American College of Rheumatology [ACR20] criteria). Both groups showed similar percentages at week 52 and improvement from week 24. In patients who achieved ACR20 at week 52, 81% maintained their ACR20 response at week 100. Minimal disease activity was defined as a combination of joint and skin symptoms, affected body surface area, pain, and physical functioning. At week 100, 38% of the continuous risankizumab group and 35% of the inactive drug/risankizumab group achieved minimal disease activity. Percentages were similar at week 52 and higher than week 24 in both groups. In patients who achieved minimal disease activity at week 52, 81% maintained response at week 100. All other measures of treatment responses showed similar patterns from the start of risankizumab through week 100. Risankizumab was considered generally safe by the treating physicians.
Hidradenitis suppurativa (HS) is a chronic, immune-mediated skin condition characterized by inflammatory lesions that can cause pain, impaired physical activity, and reduced quality of life. This study evaluated the efficacy and safety of risankizumab, a humanized immunoglobulin G1 monoclonal antibody that specifically inhibits interleukin 23 by binding to its p19 subunit, for the treatment of HS.This phase II multicenter, randomized, placebo-controlled, double-blind study investigated the efficacy and safety of risankizumab in patients with moderate-to-severe HS. Patients were randomized 1:1:1 to receive subcutaneous risankizumab 180 mg; risankizumab 360 mg; or placebo at weeks 0, 1, 2, 4, and 12. Patients initially randomized to placebo received blinded risankizumab 360 mg at weeks 16, 17, and 18; patients initially randomized to risankizumab received blinded matching placebo at the same time points. From weeks 20-60, all patients received open-label risankizumab 360 mg every 8 weeks. The primary endpoint was the achievement of HS Clinical Response (HiSCR) at week 16. Safety was assessed by monitoring of treatment-emergent adverse events (TEAEs).A total of 243 patients were randomized (risankizumab 180 mg, n = 80; risankizumab 360 mg, n = 81; placebo, n = 82). HiSCR was achieved by 46.8% of patients with risankizumab 180 mg, 43.4% with risankizumab 360 mg, and 41.5% with placebo at week 16. The primary endpoint was not met, and the study was terminated early. Incidence of TEAEs, severe TEAEs, TEAEs considered possibly related to study drug, and TEAEs leading to discontinuation of study drug were generally low and comparable across treatment groups.Risankizumab does not appear to be an efficacious treatment for moderate-to-severe HS. Future studies to understand the complex molecular mechanisms underlying HS pathogenesis and develop improved therapies are warranted.ClinicalTrials.gov identifier: NCT03926169.
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