Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised, double-blind, phase 3 KEEPsAKE 1 trial

ObjectiveTo evaluate risankizumab, a biological therapy that inhibits interleukin 23, in patients with active psoriatic arthritis (PsA) who have responded inadequately or are intolerant to ≥1 conventional synthetic disease-modifying antirheumatic drug (csDMARD).MethodsIn the randomised, placebo-controlled, double-blind KEEPsAKE 1 trial, 964 patients with active PsA were randomised (1:1) to receive risankizumab 150 mg or placebo at weeks 0, 4 and 16. The primary endpoint was the proportion of patients achieving ≥20% improvement in American College of Rheumatology criteria (ACR20) at week 24. Here, we report the results from the 24-week double-blind period; the open-label period with all patients receiving risankizumab is ongoing.ResultsAt week 24, a significantly greater proportion of patients receiving risankizumab achieved the primary endpoint of ACR20 (57.3% vs placebo, 33.5%; p<0.001). Significant differences were also observed for risankizumab versus placebo for the first eight ranked secondary endpoints, including skin and nail psoriasis endpoints, minimal disease activity and resolution of enthesitis and dactylitis (p<0.001). Adverse events and serious adverse events were reported at similar rates in the risankizumab and placebo groups. Serious infections were reported for 1.0% and 1.2% of patients receiving risankizumab and placebo, respectively. There was one death in the risankizumab group (urosepsis deemed unrelated to the study drug).ConclusionsRisankizumab treatment results in significantly greater improvement of signs and symptoms of PsA compared with placebo and is well tolerated in patients with active PsA who have responded inadequately or are intolerant to ≥1 csDMARD.Trial registration numberNCT03675308.

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Longterm Safety and Efficacy of Subcutaneous Tocilizumab Monotherapy: Results from the 2-year Open-label Extension of the MUSASHI Study

The Journal of Rheumatology ◽

10.3899/jrheum.140665 ◽

2015 ◽

Vol 42 (5) ◽

pp. 799-809 ◽

Cited By ~ 27

Author(s):

Atsushi Ogata ◽

Koichi Amano ◽

Hiroaki Dobashi ◽

Masayuki Inoo ◽

Tomonori Ishii ◽

...

Keyword(s):

Adverse Events ◽

Disease Activity ◽

Additional Treatment ◽

Joint Disease ◽

Open Label ◽

Serious Adverse Events ◽

Double Blind ◽

Safety And Efficacy ◽

American College Of Rheumatology ◽

Open Label Extension

Objective.To evaluate the longterm safety and efficacy of subcutaneous tocilizumab (TCZ-SC) as monotherapy in patients with rheumatoid arthritis (RA).Methods.Of 346 patients who received 24 weeks of double-blind treatment with either TCZ-SC monotherapy, 162 mg every 2 weeks (q2w); or intravenous TCZ (TCZ-IV) monotherapy, 8 mg/kg every 4 weeks; 319 patients continued to receive TCZ-SC q2w in the 84-week open-label extension (OLE) of the MUSASHI study (JAPICCTI-101117). Efficacy, safety, and immunogenicity were evaluated for all patients treated with TCZ during 108 weeks.Results.The proportions of patients who achieved American College of Rheumatology 20/50/70 responses, low disease activity [28-joint Disease Activity Score (DAS28) ≤ 3.2], or remission (DAS28 < 2.6) at Week 24 were maintained until Week 108. The incidences of adverse events and serious adverse events were 498.3 and 16.9 per 100 patient-years (PY), respectively. The overall safety of TCZ-SC monotherapy was similar to that of TCZ-IV monotherapy. Rates of injection site reactions (ISR) through 108 weeks remained similar to rates through 24 weeks. ISR were mild and did not cause any patient withdrawals. No serious hypersensitivity events (including anaphylactic reactions) occurred. Anti-TCZ antibodies were present in 2.1% of patients treated with TCZ-SC monotherapy.Conclusion.TCZ-SC monotherapy maintained a favorable safety profile and consistent efficacy throughout the 108-week study. Like TCZ-IV, TCZ-SC could provide an additional treatment option for patients with RA.

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Upadacitinib for psoriatic arthritis refractory to biologics: SELECT-PsA 2

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-218870 ◽

2020 ◽

pp. annrheumdis-2020-218870

Author(s):

Philip J Mease ◽

Apinya Lertratanakul ◽

Jaclyn K Anderson ◽

Kim Papp ◽

Filip Van den Bosch ◽

...

Keyword(s):

Psoriatic Arthritis ◽

Adverse Events ◽

Kinase Inhibitor ◽

Signs And Symptoms ◽

Janus Kinase ◽

Inadequate Response ◽

Double Blind ◽

Clinical Trial Registration ◽

American College Of Rheumatology ◽

Trial Drug

BackgroundUpadacitinib is a Janus kinase inhibitor under evaluation for the treatment of psoriatic arthritis (PsA). We evaluated upadacitinib in patients with PsA and prior inadequate response or intolerance to at least one biologic disease-modifying antirheumatic drug (DMARD).MethodsIn this 24-week randomised, placebo-controlled, double-blind, phase 3 trial, 642 patients were randomised (2:2:1:1) to once per day upadacitinib 15 mg or 30 mg, placebo followed by upadacitinib 15 mg or placebo followed by upadacitinib 30 mg at week 24. The primary endpoint was the proportion of patients achieving American College of Rheumatology (ACR) 20 response at week 12. Achievement of minimal disease activity (MDA) was assessed at week 24. Treatment-emergent adverse events are reported for all patients who received at least one dose of trial drug.ResultsAt week 12, significantly more patients receiving upadacitinib 15 mg and 30 mg versus placebo achieved ACR20 (56.9% and 63.8% vs 24.1%; p<0.001 for both comparisons). At week 24, MDA was achieved by more upadacitinib 15 mg-treated (25.1%) and 30 mg-treated patients (28.9%) versus placebo (2.8%; p<0.001 for both comparisons). Generally, the rates of treatment-emergent adverse events were similar with placebo and upadacitinib 15 mg and higher with upadacitinib 30 mg at week 24. Rates of serious infections were 0.5%, 0.5% and 2.8% with placebo, upadacitinib 15 mg and upadacitinib 30 mg, respectively.ConclusionIn this trial of patients with active PsA who had inadequate response or intolerance to at least one biologic DMARD, upadacitinib 15 mg and 30 mg was more effective than placebo over 24 weeks in improving signs and symptoms of PsA.Clinical trial registration numberNCT03104374

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Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised, double-blind, phase 3 KEEPsAKE 2 trial

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-221048 ◽

2021 ◽

pp. annrheumdis-2021-221048

Author(s):

Andrew Östör ◽

Filip Van den Bosch ◽

Kim Papp ◽

Cecilia Asnal ◽

Ricardo Blanco ◽

...

Keyword(s):

Psoriatic Arthritis ◽

Primary Endpoint ◽

Inadequate Response ◽

Efficacy And Safety ◽

Phase 3 ◽

Serious Adverse Events ◽

Double Blind ◽

American College Of Rheumatology ◽

Patient Reported ◽

Secondary Endpoints

ObjectivesRisankizumab is an interleukin-23 inhibitor under study for the treatment of patients with psoriatic arthritis (PsA). The phase 3 KEEPsAKE 2 trial investigated the efficacy and safety of risankizumab versus placebo in patients with active PsA who had previous inadequate response or intolerance to ≤2 biological therapies (Bio-IR) and/or ≥1 conventional synthetic disease-modifying antirheumatic drug (csDMARD-IR). Results through week 24 are reported here.MethodsAdults with PsA who were Bio-IR and/or csDMARD-IR were randomised to receive subcutaneously administered risankizumab 150 mg or placebo at weeks 0, 4 and 16 during a 24-week, double-blind treatment period. The primary endpoint was the proportion of patients who achieved ≥20% improvement in American College of Rheumatology score (ACR20) at week 24. Secondary endpoints assessed key domains of PsA and patient-reported outcomes.ResultsA total of 444 patients (median age 53 years, range 23–84 years) were randomised to risankizumab (n=224) or placebo (n=220); 206 patients (46.5%) were Bio-IR. At week 24, a significantly greater proportion of patients receiving risankizumab achieved the primary endpoint of ACR20 (51.3% vs 26.5%, p<0.001) and all secondary endpoints (p<0.05) compared with placebo. Serious adverse events were reported for 4.0% and 5.5% of risankizumab-treated and placebo-treated patients, respectively; serious infections were reported for 0.9% and 2.3%, respectively.ConclusionTreatment with risankizumab resulted in significant improvements versus placebo in key disease outcomes and was well tolerated in patients with PsA who were Bio-IR and/or csDMARD-IR.Trial registration numberNCT03671148.

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Upadacitinib in patients with psoriatic arthritis and an inadequate response to non-biological therapy: 56-week data from the phase 3 SELECT-PsA 1 study

RMD Open ◽

10.1136/rmdopen-2021-001838 ◽

2021 ◽

Vol 7 (3) ◽

pp. e001838

Author(s):

Iain B McInnes ◽

Koji Kato ◽

Marina Magrey ◽

Joseph F Merola ◽

Mitsumasa Kishimoto ◽

...

Keyword(s):

Psoriatic Arthritis ◽

Adverse Events ◽

Severity Index ◽

Inadequate Response ◽

Phase 3 ◽

Serious Adverse Events ◽

Double Blind ◽

American College Of Rheumatology ◽

Acr Criteria ◽

Minimal Disease

BackgroundIn SELECT-PsA 1, a randomised double-blind phase 3 study, upadacitinib 15 mg and 30 mg were superior to placebo and non-inferior to adalimumab in ≥20% improvement in American College of Rheumatology (ACR) criteria at 12 weeks in patients with psoriatic arthritis (PsA). Here, we report 56-week efficacy and safety in patients from SELECT-PsA 1.MethodsPatients received upadacitinib 15 mg or 30 mg once daily, adalimumab 40 mg every other week for 56 weeks or placebo through week 24 switched thereafter to upadacitinib 15 mg or 30 mg until week 56. Efficacy endpoints included the proportion of patients achieving ≥20%/50%/70% improvement in ACR criteria (ACR20/50/70), ≥75%/90%/100% improvement in Psoriasis Area and Severity Index (PASI75/90/100), minimal disease activity (MDA) and change from baseline in modified total Sharp/van der Heijde Score. Treatment-emergent adverse events per 100 patient years (PY) were summarised.ResultsConsistent with results through week 24, ACR20/50/70, PASI75/90/100 and MDA responses were maintained with upadacitinib through week 56 and were generally numerically higher than with adalimumab; inhibition of radiographic progression was also maintained. Patients who switched from placebo to upadacitinib exhibited comparable improvements at week 56 as patients originally randomised to upadacitinib. The rates of serious adverse events were 9.1 events/100 PY with upadacitinib 15 mg and 12.3 events/100 PY with upadacitinib 30 mg. Two deaths were reported in each of the upadacitinib groups.ConclusionEfficacy across various domains of PsA were maintained with upadacitinib 15 mg and 30 mg through week 56 with no new safety signals observed.

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Effects of BI 655064, an antagonistic anti-CD40 antibody, on clinical and biomarker variables in patients with active rheumatoid arthritis: a randomised, double-blind, placebo-controlled, phase IIa study

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2018-214729 ◽

2019 ◽

Vol 78 (6) ◽

pp. 754-760 ◽

Cited By ~ 14

Author(s):

Sudha Visvanathan ◽

Stefan Daniluk ◽

Rafał Ptaszyński ◽

Ulf Müller-Ladner ◽

Meera Ramanujam ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Bone Resorption ◽

Primary Endpoint ◽

Study Drug ◽

Nuclear Factor Κb ◽

Inadequate Response ◽

Serious Adverse Events ◽

Double Blind ◽

Autoantibody Production ◽

Bone Resorption Markers

ObjectiveTo evaluate the safety, efficacy and therapeutic mechanism of BI 655064, an antagonistic anti-CD40 monoclonal antibody, in patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX-IR).MethodsIn total, 67 patients were randomised to receive weekly subcutaneous doses of 120 mg BI 655064 (n=44) or placebo (n=23) for 12 weeks. The primary endpoint was the proportion of patients who achieved 20% improvement in American College of Rheumatology criteria (ACR20) at week 12. Safety was assessed in patients who received at least one dose of study drug.ResultsAt week 12, the primary endpoint was not met, with 68.2% of patients treated with BI 655064 achieving an ACR20 vs 45.5% with placebo (p=0.064); using Bayesian analysis, the posterior probability of seeing a difference greater than 35% was 42.9%. BI 655064 was associated with greater changes in CD40–CD40L pathway-related markers, including reductions in inflammatory and bone resorption markers (interleukin-6, matrix metalloproteinase-3, receptor activator of nuclear factor-κB ligand), concentration of autoantibodies (immunoglobulin [Ig]G rheumatoid factor [RF], IgM RF, IgA RF) and CD95+ activated B-cell subsets. No serious adverse events (AEs) related to BI 655064 treatment or thromboembolic events occurred; reported AEs were mainly of mild intensity.ConclusionAlthough blockade of the CD40–CD40L pathway with BI 655064 in MTX-IR patients with RA resulted in marked changes in clinical and biological parameters, including reductions in activated B-cells, autoantibody production and inflammatory and bone resorption markers, with a favourable safety profile, clinical efficacy was not demonstrated in this small phase IIa study.Trial registration numberNCT01751776

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Effectiveness and Safety of Rizatriptan Benzoate 10 mg in the Treatment of Migraine Headaches

Clinical Medicine Insights Therapeutics ◽

10.4137/cmt.s4670 ◽

2010 ◽

Vol 2 ◽

pp. CMT.S4670

Author(s):

Michel Aubé ◽

Fridon Chouha ◽

Julie Vaillancourt ◽

John Sampalis

Keyword(s):

Adverse Events ◽

Real Life ◽

Study Drug ◽

Pain Severity ◽

Open Label ◽

Serious Adverse Events ◽

Over The Counter ◽

Rizatriptan Benzoate ◽

Migraine Headaches ◽

Real Life Setting

Background Patients that do not achieve therapeutic response with over the counter non-triptan medications may benefit from triptan-based treatments. Objective Phase I V, open-label, multi-center, prospective cohort study assessing the effectiveness of rizatriptan in the management of migraines for patients that have not responded to non-triptan treatment. Methods Patients were treated with one rizatriptan (MAXALT RPD®) 10 mg wafer at the onset of each migraine attack and were assessed after a minimum of one and a maximum of two consecutive headache episodes. Outcome measures included self-reported assessments (severity and duration of migraine headache) and the Migraine ACT questionnaire. Results A total of 369 patients were enrolled, of which 291 and 215 reported one and two attacks, respectively. For the first and second attacks, 47.2% and 53.9% of patients reported complete resolution of pain while 73.6% and 77.0% reported pain severity reduction within two hours of onset. Mean (SD) pain severity score (four-point Likert scale) during the 488 migraine episodes was reduced significantly ( P < 0.001) from 2.56 (0.49) at onset to 1.91 (0.85) at 30, 1.31 (1.00) at 60 and 0.84 (1.00) at 120 minutes. Similar improvements were observed for changes in Migraine ACT questionnaire scores. No treatment-related serious adverse events were reported. The most frequently reported non-serious adverse events that were attributed to the study drug were dizziness (2.2%), chest discomfort (1.1%), nausea (1.1%), and somnolence (0.8%). Conclusion In a real-life setting, rizatriptan benzoate 10 mg is effective and safe in the treatment of acute migraine headaches in patients who do not respond to non-triptan treatment.

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Overall Tolerance and Safety of Quinapril in Clinical Trials

Angiology ◽

10.1177/000331978904000410 ◽

1989 ◽

Vol 40 (4_part_2) ◽

pp. 405-415 ◽

Cited By ~ 25

Author(s):

G.J. Frank ◽

L.E. Knapp ◽

R.W. McLain ◽

Graham J. Frank

Keyword(s):

Heart Failure ◽

Adverse Events ◽

Ace Inhibitor ◽

Comprehensive Analysis ◽

Open Label ◽

Serious Adverse Events ◽

Double Blind ◽

Hypertensive Patients ◽

High Incidence ◽

Treatment Of Hypertension

A comprehensive analysis of the reporting of adverse events, with drawals due to adverse events, and serious adverse events has been con ducted on 2,010 patients treated with quinapril hydrochloride. An analysis of all events (from both double-blind and open label studies combined) showed no increase in the incidence of events reported in congestive heart failure (CHF) patients compared to hypertensive patients. When the data for all studies were combined, an age analysis showed no increase in the total reporting of ad verse events in the 379 elderly pa tients studied. The incidence of events was lower in those patients who did not take concomitant di uretic therapy. A comparison of the double-blind phases showed quinapril to have a lower incidence of adverse events than captopril, enalapril, or chlor thalidone. An analysis of the onset of events, or withrawals, did not show an increase with time on quinapril therapy, and no dose-relationship. A review of serious adverse events did not reveal an unexpected occurrence or a high incidence of serious events considered to be related to quinapril therapy. The proportion of patients who experienced "first-dose" hypo tension, or symptomatic hypotension was similar to captopril or enalapril. Quinapril, a nonsulfhydryl ACE inhibitor, has been extensively stud ied and is equally well tolerated in the young and elderly for the treatment of hypertension and CHF.

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Long-term safety, efficacy and inhibition of radiographic progression with abatacept treatment in patients with rheumatoid arthritis and an inadequate response to methotrexate: 3-year results from the AIM trial

Annals of the Rheumatic Diseases ◽

10.1136/ard.2010.139345 ◽

2011 ◽

Vol 70 (10) ◽

pp. 1826-1830 ◽

Cited By ~ 99

Author(s):

Joel M Kremer ◽

Anthony S Russell ◽

Paul Emery ◽

Carlos Abud-Mendoza ◽

Jacek Szechinski ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Radiographic Progression ◽

Incidence Rates ◽

Inadequate Response ◽

Open Label ◽

Serious Adverse Events ◽

Double Blind ◽

American College Of Rheumatology ◽

Inadequate Responders

ObjectiveTo evaluate abatacept treatment over 3 years in patients with rheumatoid arthritis (RA) refractory to methotrexate (MTX).MethodsPatients randomised to abatacept or placebo (+MTX) during the 1-year double-blind period of the Abatacept in Inadequate responders to Methotrexate (AIM) trial received open-label abatacept (+MTX) in the long-term extension (LTE). Safety was assessed for patients who received ≥1 dose of abatacept, regardless of randomisation group. Efficacy was assessed for patients randomised to abatacept who entered the LTE.Results433 and 219 patients were randomised and treated with abatacept or placebo, respectively; 378 and 161 entered the LTE. At year 3, 440/539 patients were ongoing. No unexpected safety events were observed in the LTE. By year 3, incidence rates of adverse event and serious adverse events were 249.8/100 and 15.1/100 patient-years, respectively. Incidence rates were generally stable over time. At year 3, 84.8%, 63.4% and 37.5% of patients achieved American College of Rheumatology (ACR) criteria of 20, 50 and 70, respectively, compared with 82.3%, 54.3% and 32.4% of patients at year 1. Mean changes in Genant-modified Sharp scores were reduced progressively over 3 years, with significantly greater inhibition during year 3 compared with year 2 (p=0.022 for total score).ConclusionIn MTX-inadequate responders with RA, abatacept provided consistent safety and sustained efficacy over 3 years. The data suggest an increasing inhibitory disease-modifying effect on radiographic progression.

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Safety findings from CENTURION, a phase 3 consistency study of lasmiditan for the acute treatment of migraine

The Journal of Headache and Pain ◽

10.1186/s10194-021-01343-2 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

C Tassorelli ◽

S Bragg ◽

JH Krege ◽

EG Doty ◽

PA Ardayfio ◽

...

Keyword(s):

Adverse Events ◽

Acute Treatment ◽

Motor Vehicle ◽

Specific Treatment ◽

Study Drug ◽

Control Group ◽

Phase 3 ◽

Serious Adverse Events ◽

Double Blind ◽

Vehicle Accidents

Abstract Background Lasmiditan (LTN) is a selective 5-HT1F receptor agonist for the acute treatment of migraine in adults. We present detailed safety findings from the placebo-controlled, double-blind Phase 3 study, of LTN treatment across 4 attacks (CENTURION). Methods Patients were randomized 1:1:1 to LTN 200 mg (LTN200), LTN100, or a control group that received placebo for 3 attacks and LTN50 for either the 3rd or 4th attack (1:1). Safety analyses were conducted for patients who took ≥1 dose of study drug and, in some cases, those who took all 4 doses. Results Overall, 1471 patients treated 4494 attacks. The incidences of treatment-emergent serious adverse events (SAEs) were - placebo, n=2 (0.4 %); LTN100, n=1 (0.2 %); LTN200, n=2 (0.4 %); no specific treatment-emergent SAE was reported in more than one patient. The most common treatment emergent adverse events (TEAEs) with lasmiditan were dizziness, paresthesia, fatigue, nausea, vertigo, and somnolence; the vast majority were mild or moderate in severity. The incidences of these TEAEs were highest during the first attack and decreased during subsequent attacks. For patients who experienced a common TEAE with the first attack, less than 45 % experienced the same event in subsequent attacks. Patients who did not experience an event in the 1st attack infrequently experienced the same event in subsequent attacks. The time of onset of the common TEAE ranged from ~40 min to 1 h (dependent upon TEAE) and, for individual TEAE, the onset was similar across attacks. Duration was dependent upon TEAE and attack. It was shortest for paresthesia (< 2 h for all attacks); it ranged from 1.8 to 5.5 h for other common TEAEs and was generally similar across attacks. Serotonin syndrome was reported for 2 patients post LTN dosing; there were no meaningful differences across treatment groups in suicidality; there was no evidence of an increase in motor vehicle accidents. Conclusion In this blinded, controlled, multiple-attack study, LTN was associated with generally mild or moderate CNS-related TEAEs of short duration. TEAEs tended to decrease in frequency across the 4 attacks. Trial registration NCT03670810

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The Safety and Efficacy of Oral Magnesium Pidolate in Children with Hemoglobin SC Disease.

Blood ◽

10.1182/blood.v106.11.3777.3777 ◽

2005 ◽

Vol 106 (11) ◽

pp. 3777-3777

Author(s):

Brigitta Ursula Mueller ◽

Marlen Dinu ◽

Susan Kurth ◽

Roz Bryant ◽

Elizabeth Mullen ◽

...

Keyword(s):

Adverse Events ◽

Sickle Cell ◽

Serum Magnesium ◽

Study Drug ◽

Laboratory Evaluation ◽

Controlled Study ◽

Serious Adverse Events ◽

Double Blind ◽

Efficacy Analysis ◽

Cellular Dehydration

Abstract An important characteristic of the Hb SC erythrocyte is its high intracellular Hb concentration, which is due to cell K+ loss and dehydration mediated by an abnormally active K-Cl co-transport. This pathologic state of cellular dehydration raises the intracellular concentration of Hb S, thereby increasing its tendency to polymerize. Previous studies in patients with sickle cell disease have shown that oral Mg supplements can increase erythrocyte Mg content, reduce the activity of K-Cl co-transport and diminish erythrocyte dehydration. We performed a randomized, double blind, placebo-controlled study with crossover design on oral Mg supplementation in children with HbSC disease. Methods: Two major pediatric sickle cell centers participated in this IRB-approved study: Texas Children’s Sickle Cell Center and The Children’s Hospital in Boston. Over 100 eligible patients were contacted and invited to participate. The enrolled patients or their parents/guardians gave informed consent. Patients were randomized to either receive oral Mg pidolate or placebo for 6 months followed by a wash-out period of 2 months, then followed by a 6 month period of the other agent (placebo/Mg pidolate) and 2 months wash-out. Patients were initially followed every 2 weeks, then every 4 weeks. Safety was assessed both by clinical assessment as well as laboratory evaluation, including serum magnesium levels. Results: Between January 2002 and December 2004 we enrolled 12 patients (7 males, 5 female, age range 3.9 to 16.8 years) with HbSC disease and at least one pain crisis within the last year. Only 5 patients are fully evaluable for efficacy assessment. Seven patients came off study for the following reasons: 3 for non-compliance, 2 for study violation (pharmacy dispensed wrong formulation), and 2 withdrew for personal reasons (no longer interested), but all of them were included in the safety assessment. There were 3 events that were considered probably related to study drug (or placebo): diarrhea, grade 2 once and headaches, grade 3, in 2 instances. There were 6 events possibly related to drug (or placebo): diarrhea in three patients (all grade 1) and headaches of grade 2 or 3 in three patients. All adverse events resolved without stopping the drug/placebo. The results of the intracellular Mg concentrations and thus efficacy analysis will be available after unblinding the study in September 2005. Conclusion: Mg pidolate appears to be safe and well-tolerated when used in children with HbSC disease. No serious adverse events occurred that were considered definitively related to the study drug(s). Efficacy results will be available at the time of the meeting. However, despite the fact that study was open at 2 major sickle cell centers and had relatively non-restrictive enrollment criteria, accrual was extremely slow, presumably due to the sporadic and rather low disease intensity of Hb SC disease, and several patients did not complete the study. This should be taken into consideration when designing larger studies for patients with HbSC disease exclusively.

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