Samara Rosenfeld

Filgotinib has a similar safety profile for 

, according to the findings of new research presented at the

Congress of Clinical Rheumatology East 2020

No new or unexpected safety signals were discovered, while filgotinib was generally well-tolerated and sustained efficacy up to open-label extension at 52 weeks.

Laura Coates, MBChB, MRCP, PhD, and investigators evaluated the interim safety and efficacy of filgotinib 200 mg in patients participating in EQUATOR2 at 52 weeks’ treatment. Phase 2 of the EQUATOR study, a 16-week, double-blind, randomized controlled trials demonstrated filgotinib significantly improved multiple disease domains versus placebo and was well-tolerated among patients with psoriatic arthritis. EQUATOR2 is ongoing and assessing the long-term safety and efficacy of the therapy for up to an additional 148 weeks of treatment.

Patients with active psoriatic arthritis were randomized 1:1 to receive either oral filgotinib 200 mg or placebo once daily for 16 weeks in EQUATOR. Those included were at least 18 years old with psoriatic arthritis defined by Classification for Psoriatic Arthritis criteria, were diagnosed at least 12 weeks before screening, had moderate-to-severe psoriatic arthritis (at least 5 swollen joints and at least 5 tender joints), active or history of plaque psoriasis, and insufficient response to at least 1 conventional synthetic disease-modifying antirheumatic drug (csDMARD).

Those who completed EQUATOR were eligible for EQUATOR2. In EQUATOR2, patients received open-label oral filgotinib 200 mg once daily for up to 148 weeks. Of those enrolled in EQUATOR, 87% enrolled in the open-label extension.

Overall, half of patients were female, the mean age was 50 years old, and the mean duration of psoriatic arthritis was 7 years. Some patients (15%) received prior anti-tumor necrosis factor therapy and 74% received concurrent csDMARD therapy at baseline and during the study. In the filgotinib and placebo groups, median Psoriasis Area and Severity Index score was 6.5 (IQR, 2.6-15) and 6.9 (IQR, 3.8-18.6), respectively. The mean Psoriatic Disease Activity score was 6.1 for filgotinib and 6.2 for placebo, and the mean Disease Activity Index for psoriatic arthritis score was 44 and 47.8 for filgotinib and placebo, respectively.

Total filgotinib exposure was 160 patient-years with a median time on the therapy as 66 weeks. Total placebo exposure during the core EQUATOR study was 20 patient-years with a median time on placebo as 16 weeks.

Treatment-emergent adverse events were mostly mild or moderate. There was 1 patient who reported a serious, non-fatal, drug-related treatment-emergent adverse event with filgotinib during the EQUATOR2 open-label extension study. One patient treated with filgotinib died on day 106 of the core EQUATOR study due to a serious drug-related treatment-emergent adverse event of pneumonia. There was a low incidence of treatment-emergent adverse events, except for respiratory tract infection which occurred at a rate of 46.2 per 100 patient-years of exposure. Decreased lymphocyte and neutrophil counts were the most notable abnormal changes in laboratory parameters with filgotinib treatment.

At week 52 of the open-label extension, 81%, 55%, and 33% of patients achieved ACR20/50/70 responses. Response rates were maintained over time from open-label extension week 16 to week 52. At week 52, 34% of patients fulfilled criteria for minimal disease activity. Such rates were maintained over time from week 16 to week 52.

The investigators noted the safety profile of filgotinib in patients with psoriatic arthritis was consistent with findings from rheumatoid arthritis studies with no new or unexpected safety signals. In EQUATOR2, the therapy was well-tolerated and showed sustained efficacy up to open-label extension week 52.

EDITOR's NOTE:  This article originally appeared on our sister site HCPLive.com.

Long-Term Safety of Filgotinib in Patients with Psoriatic Arthritis: Week 52 Safety Data from a Phase 2 Open-Label Extension Study

,” was published as part of the Congress of Clinical Rheumatology East 2020 meeting.

Articles

The investigational JAK inhibitor filgotinib―which is under study as a treatment for a number of rheumatic diseases―has been shown to be safe and well tolerated in psoriatic arthritis patients.


JAK1 Inhibitor Filgotinib Meets PsA Safety Profile

A new study shows that biomechanical footwear improved osteoarthritis knee pain at 24 weeks as compared to patients in a control group who wore traditional footwear. The results, although statistically significant, need to be replicated to prove clinical importance, according to Peter Juni, M.D., FESC and a team of investigators writing in 

Juni, from the Applied Health Research Center at Li Ka Shing Knowledge Institute in Toronto, Canada, and colleagues assessed the effect of a biomechanical footwear therapy versus control footwear over 24 weeks of follow-up. The team hypothesized that individually calibrated biomechanical footwear therapy could improve pain and physical function in people with symptomatic knee osteoarthritis.

The investigators enrolled men and nonpregnant women >40 years old who had symptomatic, radiologically confirmed knee osteoarthritis according to criteria from the American College of Rheumatology. The participants had knee pain last >6 months and a score of >3 on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale. If a patient had a history of inflammatory rheumatic disease, had undergone knee surgery during the prior 6 months, or had a planned hip or knee surgery within 24 weeks of baseline, they were excluded from the study.

Each participant was randomized 1:1 to either the biomechanical footwear group or to the control footwear group. The biomechanical footwear consisted of 2 shoes with 2 convex adjustable rubber pods screwed to the outsole at the heel and forefoot. The control footwear was designed to have a similar appearance but with pods embedded in the transparent outsole, so they were visible but did not create a convex walking surface.

In both groups, participants underwent an initial fitting of their footwear at baseline and during recalibration at 4, 8, 12, and 16 weeks of follow-up. The participants were told to use the footwear during indoor activities for 30 minutes each day during the first week, with increases of 10 minutes per week on average.

At 6 weeks, participants used the footwear to walk outdoors. Participants also discontinued their regular pain medication and were told to avoid other interventions like physical therapy.

The primary outcome was knee pain at 24 weeks of follow-up assessed with the WOMAC (0=no symptoms to 10=extreme symptoms). Additional outcomes included WOMAC physical function and stiffness subscores and the WOMAC global score at 24 weeks of follow-up.

Overall, there were 220 participants randomized with a mean age of 65.2 years old and 47.3% women. Of the participants, 219 received the treatment and 96.8% completed follow-up.

At follow-up, the mean standardized WOMAC pain score improved from 4.3 to 1.3 in the biomechanical footwear group. In the control group, the score improved from 4 to 2.6 (between-group difference in scores at 24 weeks follow-up, -1.3 [95% CI, -1.8 to -.9]; P<.001).

The results were similar for WOMAC physical function subscore (between-group difference, −1.1 [95% CI, −1.5 to −0.7]), WOMAC stiffness subscore (between-group difference, −1.4 [95% CI, −1.9 to −0.9]), and WOMAC global score (between-group difference, −1.2 [95% CI, −1.6 to −0.8]) at 24 weeks of follow-up. There were 3 serious adverse events in the biomechanical footwear group compared with 9 in the control group (2.7% vs 8.3%), but none were related to treatment.

Additional research is needed to assess the long-term efficacy and safety, along with replication, before the results are deemed clinically valuable.

“Effect of Biomechanical Footwear on Knee Pain in People With Knee Osteoarthritis,” 

NOTE:  Samara Rosenfeld is a writer with our sister publication, 

A new study shows that biomechanical footwear improved osteoarthritis knee pain at 24 weeks as compared to patients in a control group who wore traditional footwear. The results, although statistically significant, need to be replicated to prove clinical importance, researchers reported in JAMA.

Study Shows Footwear Relieves Osteoarthritic Knee Pain

Pregnant women who took fluconazole orally had a higher risk of giving birth to a baby with muscle and bone malformation, shows a new study published in

Using oral fluconazole in the first trimester was not associated with oral clefts or conotruncal malformations but was associated with musculoskeletal malformations.

“Oral fluconazole during the first trimester, especially prolonged treatment at higher than commonly used doses, should be prescribed with caution, and topical azoles should be considered as an alternative treatment,” Yanmin Zhu, MS, PhD, and study authors said in a statement.

Zhu and the team of Boston-based colleagues used a cohort of pregnancies publicly insured in the US and data from the nationwide Medicaid Analytic eXtract 2000-14. The investigators examined the risk of congenital malformations associated with exposure to oral fluconazole at commonly used doses in the first trimester for the treatment of vulvovaginal candidiasis.

The database contained information on a patient’s Medicaid enrollment, demographics, diagnoses, and all procedures at all outpatient and inpatient settings, and dispensed records for outpatient prescription drugs for reimbursement. In the database, a pregnancy cohort was established to study the safety of drug treatment during pregnancy.

The investigators identified pregnant women aged 12-55 years old who were continuously enrolled in Medicaid from >3 months before the last menstrual period to >1 month after delivery. Also included were those with liveborn infants enrolled from birth to >3 months afterward.

Zhu and the team excluded pregnancies with a chromosomal abnormality or exposure to a teratogenic drug during trimester 1. Among diagnoses of oropharyngeal or esophageal candidiasis, women were also excluded if they had an inpatient diagnosis of fungal infection between 90 days before the last menstrual period and the end of the first trimester.

Pregnant women were identified as taking fluconazole if they filled >1 prescription during the first trimester and had no dispensing for other oral antifungal agents between 90 days before the last period and the end of the first trimester. There was an initial reference group of pregnant women who filled >1 prescription for topical azoles during their first trimester and did not dispense for oral antifungal agents during baseline and the first trimester.

The investigators chose topical azoles including butoconazole, clotrimazole, miconazole, terconazole, tioconazole, and nystatin in the primary reference group to reduce the risk of confounding by indication. The second reference included women with no oral antifungal agent prescriptions during baseline and the first trimester. What’s more, the team classified women exposed to fluconazole into 3 dose groups: 150 mg, >150 mg to <450 mg, and >450 mg.

The primary outcomes of the study were musculoskeletal malformations, oral clefts, and conotruncal malformations. Additional measures included subgroups of such malformations and cardiac malformations overall.

Nearly 2 million pregnancies were included in the cohort, or which, 1.9% were exposed to oral fluconazole and 4.2% were exposed to topical azoles during the first trimester. Those in the fluconazole group were more likely to be black, have a vulvovaginal candidiasis diagnosis or other infections, be overweight or obese and have hypertension and diabetes, use other drugs, and use healthcare facilities more often than women with pregnancies not exposed to fluconazole.

Per 10,000 pregnancies exposed to fluconazole, the risk of musculoskeletal malformations was 52.1 (95% CI, 44.8-59.3) versus 3.8 (95% CI, 37.1-38.9) per 10,000 pregnancies not exposed to fluconazole. There was an unadjusted relative risk of 1.37 (95% CI, 1.19-1.58). For pregnancies exposed to topical azoles, the risk was 37.3 (95% CI, 33.1-41.4).

After comparing oral fluconazole to topical azoles, there was an unadjusted relative risk of 1.4 (95% CI, 1.17-1.67). Overall, after adjusting for all confounding variables, compared with topical azoles, the relative risk was the relative risk compared with topical azoles was 1.3 (95% CI, 1.09-1.56) and the risk difference was 12.15 (95% CI, 3.69-20.6) per 10,000 pregnancies.

For conotruncal malformations, the risk was 9.6 (95% CI, 6.4-12.7) per 10,000 pregnancies exposed to fluconazole, 7.5 (95% CI, 7.1-7.9) per 10,000 pregnancies not exposed to fluconazole, and 8.3 (95% CI, 6.3-10.3) per 10,000 pregnancies exposed to topical azoles. The risk of musculoskeletal malformations was 52.1 (95% CI, 44.8-59.3) per 10,000 pregnancies exposed to fluconazole versus 37.3 (95% CI, 33.1-41.4) per 10,000 pregnancies exposed to topical azoles.
	Oral clefts risks were 9.3 (95% CI, 6.2-12.4) for those exposed to fluconazole versus 10.6 (95% CI, 8.4-12.8) for topical azoles. After fine stratification, there was an adjusted relative risk of 1.3 (95% CI, 1.09-1.56) for musculoskeletal malformations, 1.04 (95% CI, .7-1.55) for conotruncal malformations, and .91 (95% CI, .61-1.35) for oral clefts.

“Our study confirmed an increase in the risk of musculoskeletal malformations if fluconazole is used during the first trimester, and refuted large increased risks of conotruncal malformations, oral clefts, and other specific types of malformations,” Zhu and the investigators concluded.

The study, “Oral fluconazole use in the first trimester and risk of congenital malformations: population-based study cohort,” was published online in 

Pregnant women who took fluconazole orally had a higher risk of giving birth to a baby with muscle and bone malformation, shows a new study published in The BMJ.

Author | Samara Rosenfeld

Articles

JAK1 Inhibitor Filgotinib Meets PsA Safety Profile

Study Shows Footwear Relieves Osteoarthritic Knee Pain

Oral Fluconazole Use in the First Trimester Linked to Musculoskeletal Malformations