New findings suggest fewer than one-third of patients in the Archway trial of the 

Port Delivery System (PDS) with ranibizumab

 experienced clinically meaningful central subfield thickness (CST) fluctuations over 96 weeks.

The data additionally show visual acuity was similar across treatment arms, but those with CST fluctuations were observed to have experienced worse visual acuity. 

American Society of Retina Specialists 40th Annual Scientific Meeting

, presenting author Veeral Sheth, MD, University Retina, discussed the findings of the post-hoc analysis and what may be next for PDS. 

He described the background of the study, particuarly highlighting the correlation between retinal thickness fluctuations and vision changes. 

"Part of why people don't do well in the real world is because their retina tends to fluctuate, they get OCT variability along the course of their treatment, and over time, their vision declines," Sheth said. "We know with newer agents, we want durability. Because I think that is really what keeps the anatomy stable."

ARCHWAY patients were implanted with PDS with a Q24 week refill and were compared to those who received monthly ranibizumab. The data show nearly 70% of patients in both groups had no retinal thickness fluctuations.

"In that small percentage where we did see some fluctuations, those patients did tend to do a little worse from a vision standpoint, which is exactly what you would expect," Sheth noted. "But, the magnitude of that change wasn't very large at all."

Most patients did well and on average, ended up at 20/30 vision at the end of the study. The more durable the agent, the better the patient will do in the long run, Sheth said. He added that newer agents are lasting longer, which clincians have been looking for for a long time,

"Now that we've got them, we're starting to put them in place in the real world and starting to see the benefits of that and more importantly, patients are seeing the benefits of that," Sheth said. 

He spoke on further safety signals of PDS itself, noting that higher rates of endophthalmitis was observed.

"I think that's why it's really important for people to be well educated on the surgical technique," Sheth said. "I think you see in the clinical trials that we learned a lot. As we modified our techniques, it looks like the procedure itself became safer over time."

Sheth noted that in a few years, clinicians will learn more about their patients and the vision outcomes. Historically, from a treatment standpoint, compliance and treatment burden issues tend to come up over time.

"With these new delivery devices, especially with PDS, if you're only having to refill it every six months, you're likely to see better outcomes in the long run," he added. 

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Overall 70% of the patients in both PDS with ranibizumab and ranibizumab alone had almost no retinal thickness fluctuations.

Veeral Sheth, MD: Insights Into CST Fluctuations, Vision Outcomes with PDS Treatment 

The Explorer7 study assessed the efficacy and safety of prophylactic treatment with concizumab in individuals living with 

 with inhibitors and found that the safety and tolerability of the drug was within the expected range and no thromboembolic events were reported. 

The anti-tissue factor pathway inhibitor (TFPI) antibody is in development and not yet approved by regulatory authorities to provide patients with once-daily prophylactic treatment. It's administered subcutaneously for all hemophilia types. 

Those with hemophilia can experience "bleeds" as a result of the body's inability to produce blood clots due to the bleeding disorder and need to be treated with medication, especially following a traumatic event. 

However, in some individuals, the immune system develops inhibitors that can block these replacement therapies that are used to allow proper clotting. It's estimated that 30% of those with hemophilia A and 1-3% of hemophilia B have inhibitors. 

According to the phase 3 data presented at the International Society of Thrombosis and Haemostasis Annual Congress (ISTH 2022) in London, UK, investigators observed an 86% reduction in treated spontaneous and traumatic bleeds when patients with inhibitors were on concizumab prophylaxis. 

“One of the most critical complications in the treatment of haemophilia is the development of inhibitors, as they render standard replacement therapy ineffective and severely limit treatment options for haemophilia B,” lead investigator Victor Jiménez-Yuste, MD, Haematology Department, La Paz University Hospital, said in a 

The estimated mean ABR of 1.7 in the treated population compared with 11.8 in those without prophylaxis demonstrated that the study fulfilled its primary objective. The overall median ABR of concizumab was 0 and 9.8 for no prophylaxis. No treated bleeds occurred in 21, or 63.6%, of individuals on concizumab while in the control group only 10.5%, or 2 people, had an absence of treated bleeds throughout the study. 

“Based on the results of the explorer7 study, there is a potential for concizumab to become a new treatment option for people living with haemophilia A or B with inhibitors," Jiménez-Yuste said. 

The Explorer7 study primary analysis compared the number of treated spontaneous and traumatic bleeding episodes, measured as ABR, between arms 1 and 2 of the ongoing clinical trial program for concizumab. For the evaluation, 133 males (aged 12 years and over) were randomised 1:2 to either a no prophylaxis (arm 1; ≥24 weeks) or concizumab prophylaxis (arm 2; ≥32 weeks) or assigned to concizumab prophylaxis (arm 3 and 4). 

A regulatory approval for the prophylactic treatment of hemophilia A or B with inhibitors is expected to be submitted by the developing company Novo Nordisk during the second half of 2022 in the US and Japan, and during 2023 in the EU and UK. 

“The treatment of haemophilia is complex and no one treatment fits all,” Martin Lange, executive vice president and head of Development at Novo Nordisk said. “Concizumab offers the potential for everyday protection for people living with haemophilia and provides an important potential addition to our haemophilia offering, especially in the haemophilia B with inhibitor population who currently have limited treatment options.”

Articles

The phase 3 data presented at the ISTH 2022 Annual Congress show an 86% reduction of treated bleeds in patients with hemophilia A or B with inhibitors.

Concizumab Reduces Treated Bleeds in Hemophilia A or B with Inhibitors

New findings suggest faricimab is showing efficacy in both difficult-to-treat and treatment-naive patients with 

neovascular age-related macular degeneration (nAMD)

Safety signals were additionally considered positive, as no cases of intraocular inflammation were reported in the 377 patients with 770 injections.

“In the future, we will hopefully be looking at durability, but for this study we were looking at the safety and efficacy after 1 injection,” said lead study author Carl Danzig, MD, Director of Vitreoretinal Services, Head of Retina Clinical Research, Rand Eye Institute.

The late-breaking findings were presented at the 

The TRUCKEE study evaluated both the efficacy and safety of faricimab in real-world patients with nAMD. The target population were treatment-naive patients, but an emphasis was put on high-need patients, such as those who require frequent injections due to persistent disease activity.

Ongoing data collection is being undertaken to encompass the demographics, prior treatment history, efficacy, and safety. Efficacy measurements include vision, central subfield thickness, retinal fluid, and pigment epithelial detachments.

In total, 377 patients or 421 eyes were treated with faricimab and considered the study population. Those patients were administered a total of 770 intravitreal injections. There was follow-up data after faricimab injection available for 236 eyes.

Investigators looked at follow-up of the population with 20/400 vision or better, based on the conversion from Snellen to ETDRS. The mean age of the patients was 79.6 years, with 173 male (45.9%) and 204 (54.1%) female patients.

STUDY AUTHOR noted that 28 (6.6%) of these patients were treatment-naive, with the majority being switch patients. He added that 156 (66.1%) received aflibercept as their last anti-VEGF injection.

In those 236 eyes of the follow-up group, the vision was considered stable. These patients received their faricimab injection and came back for a follow-up. Regarding efficacy, data show ETDRS increased from a mean of 62.8 letters at baseline to 63.3 letters at the follow-up (change, +0.5 letters).

Moreover, there was an observed improvement in anatomy in both central subfield thickness (CST) and pigment epithelial detachments (PED) height. The CST improved from a mean of 332.3 μM at baseline to 300.2 μM at follow-up (change, -32.1 μM) and PED height improved from 262.5 μM at baseline to 248.6 μM at follow-up (change, -13.9 μM).

When looking at switch patients from any anti-VEGF, investigators observed stable vision and encouraging anatomic improvements. Data show ETDRS letters improved from 62.9 letters at baseline to 63.6 letters at follow-up (change, +0.7 letters), while CST improved from 327.9 μM at baseline to 301.1 μM at follow-up (change, -26.8 μM). The PED height was 273.1 μM at baseline and 267.3 μM at follow-up (change, -5.8 μM).

Regarding safety outcomes, there were no observed cases of intraocular inflammation, retinal vasculitis, or retinal artery occlusions. A single case of culture positive endophthalmitis was reported, which was treated and the vision returned to baseline.

More data on the ongoing TRUCKEE study is expected to be presented at future meetings later this year and next year.

“Real World Efficacy, Durability and Safety of Faricimab in Neovascular Age-Related Macular Degeneration: The TRUCKEE Study,” was presented at ASRS 2022.

Real-world patients showed improvement in visual acuity and anatomic parameters, but are still at an early time point in TRUCKEE study. 

Faricimab Shows Efficacy in Treatment-Naive, Difficult-to-Treat Patients with nAMD 

New findings suggest pegcetacoplan shifts the distribution across lesion growth quartiles in assessment of the progression of 

Investigators observed data show a similar treatment effect observed in the primary analysis of these 2 trials.

“This analysis provides additional data on factors that may impact lesion growth; with further research, these findings may aid in identifying populations that may have a greater response to pegcetacoplan,” wrote lead study author Roger Goldberg MD, MBA, Vitreoretinal Surgeon, Bay Area Retina Associates.

The phase 3 randomized, double-masked OAKS and DERBY assessed the efficacy and safety of investigational intravitreal pegcetacoplan for GA treatment, secondary to age-related macular degeneration. A detailed analysis by category of change in GA lesion size was reported in eyes treated with pegcetacoplan or sham.

Both studies had the primary endpoint of change in GA lesion size via fundus autofluorescence imaging from baseline to month 12. The patients were pooled across study arms and assigned to quartiles defined by the amount of lesion growth (mm

) over 12 months. The quartiles were separated into:

Quartile (Q)1 (slow progressors; OAKS: <0.93, DERBY: <1.025)

Q2 (OAKS: ≥0.93 – <1.48, DERBY: ≥1.025 – <1.62)

Q3 (OAKS: ≥1.48 – <2.27, DERBY: ≥1.62 – <2.45)

Inclusion in the analysis was restricted to those with a month 12 lesion growth measurement. Data show OAKS and DERBY had 494 and 461 respective patients included in the analysis.

Investigators reported that in both OAKS and DERBY, evidence of a treatment effect of pegcetacoplan was seen in the distribution of the included patients across the quartiles. They found the slowest progression quartile (Q1) had a higher proportion of patients treated with pegcetacoplan monthly (39% and 36%) or every other month (36% and 35%), compared to those in the sham cohort (25% and 30%).

Moreover, data show relatively more sham patients (42% and 37%) in the fastest growing quartile (Q4) compared to patients treated with pegcetacoplan monthly (27% and 29%) or every other month (31% and 34%), in OAKS and DERBY, respectively.

Baseline study eye lesion size was larger in the fast progressor group compared to the slow progressor group (OAKS: 9.5 mm

Additionally, the fast progressor group had a higher proportion of individuals with extrafoveal study eye lesion location, multifocal study eye GA, bilateral GA, double-layer sign present in the study eye and pseudodrusen present in the study eye, according to investigators.

The fast progression group further had a lower proportion of patients with >20 SE intermediate or large drusen or choroidal neovascularization in the fellow eye, investigators noted.

“Assessment of Geographic Atrophy Lesion Progression in the Phase 3 OAKS and DERBY Trials,” was presented at 

Evidence of pegcetacoplan treatment effect observed in the distribution of patients across quartiles in both OAKS and DERBY. 


Pegcetacoplan Shifts Distribution Across Lesion Growth Quartiles In GA Treatment 

Intravitreal pegcetocoplan administered monthly or every other month was observed to be well-tolerated in patients with 

 at 12 months, according to new findings presented at the 

Led by Caroline Baumal MD, Professor, New England Eye Center, Tufts University, investigators reported additional details regarding safety outcomes in the OAKS and DERBY trials. Each evaluated investigational monthly or every-other-month intravitreal pegcetacoplan in eyes with GA secondary to age-related macular degeneration (AMD).

Both of the phase 3 trials evaluated efficacy and safety of pegcetacoplan treatment for GA. Although GA is considered a leading cause of worldwide irreversible vision loss, there is a lack of findings reported on detailed safety data for pegcetacoplan treatment.

Both OAKS and DERBY are randomized, double-masked, sham-controlled trials that enrolled patients ≥60 years old with best-corrected visual acuity (BCVA) ≥24 letters and GA area 2.5 - 17.5 mm

. Primary outcomes were considered the change from baseline to month 12 in GA lesion size measured via fundus autofluorescence in patients treated with pegcetacoplan. Safety outcomes were additionally evaluated, including the incidence of ocular and systemic treatment-emergent adverse events were evaluated.

A total of 6322 pecetacoplan injections were given across each trial at 12 months (safety set: OAKS, n = 636; DERBY, n = 620). The majority of adverse events were considered mild or moderate, according to investigators.

In the OAKS trial, 14 (6.6%), 16 (7.5%), and 8 (3.8%) patients in the monthly, every-other-month, and sham groups, respectively, had adverse events in the study eye related to treatment. In the DERBY trial, 19 (9.2%), 13 (6.3%), and 6 (2.9%) patents in the monthly, every-other-month, and sham groups, respectively have adverse events related to treatment.

Meanwhile, serious ocular adverse events in the study eye were reported for 3 (1.4%), 4 (1.9%), and 0 patients in OAKS and 1 (0.5), 0, and 2 (1.0%) patients in DERBY in the monthly, every-other-month, and sham groups, respectively.

Investigators noted a total of 4 patients discontinued treatment due to ocular adverse events in the study eye in OAKS, including 1 in the monthly group, followed up 2 in the every-other-month group and 1 in the sham group. In Derby, 3 patients discontinued treatment due to ocular adverse events, including 2 in the sham group and 1 in the every-other-month group.

In the combined trials, the investigator-reported events of new onset exudative AMD (eAMD) in the study eye were reported in 25 (6.0%), 17 (4.1%), and 10 (2.4%) patients in the monthly, every-other-month, and sham groups.

The team reported those study eyes that developed eAMD continued treatment with pegcetacoplan and received anti-VEGF therapy. They additionally reported a total of 13 study eyes across both studies receiving pegcetacoplan experienced intraocular inflammation (IOI), with the majority of cases considered mild.

From the 13 study eyes, 10 were able to resume pegcetacoplan without recurrence of IOI. The rate of IOI per injection was 0.22%, according to the data and no cases of vasculitis or occlusive vasculitis were reported.

Moreover, investigators reporting adverse events related to intraocular pressure in the study eye in 8 (3.8%), 10 (4.7%), and 1 (0.5%) patients in OAKS and in 7 (3.4%), 7 (3.4%), and 0 patients in DERBY in the monthly, every-other-month, and sham groups.

“Safety of Intravitreal Pegcetacoplan for Geographic Atrophy: 12-Month Results of the OAKS and DERBY Trials,” was presented at 

FDA Accepts NDA for Pegcetacoplan for Treatment of Geographic Atrophy

Pegcetacoplan Shifts Distribution Across Lesion Growth Quartiles In GA Treatment

The Impact of a Pegcetacoplan FDA Approval for Geographic Atrophy

Monthly or every other month intravitreal pegcetacoplan reported to be tolerated in DERBY and OAKS trials. 

Intravitreal Pegcetacoplan Well-Tolerated in Patients with Geographic Atrophy

New findings suggest ellipsoid zone integrity in eyes with 

 appeared to be a key driver for visual acuity outcomes in eyes without the presence of fluid.

Overall outcomes were best achieved in those eyes without fluid and ellipsoid zone integrity preservation, making it an important consideration for fluid tolerance in the management of the disease state.

“Achieving a dry retina with ellipsoid zone maintenance may provide the optimal outcome,” wrote lead study author Justis Ehlers MD, FASRS, Associate Professor, Cleveland Clinic Lerner College of Medicine.

The team of investigators, led by Ehlers, assessed the association of best corrected visual acuity (BCVA) with retinal fluid, exudative volatility, and ellipsoid zone integrity in eyes with nAMD, utilizing a machine learning-enhanced feature extraction system. They aimed to provide a next-generation, in-depth feature assessment to comprehensively characterize the relationship of fluid and visual acuity in patients with nAMD.

The reported data were from the treatment agnostic analysis of the Phase III HAWK nAMD clinical trial (n = 652). They measured fluidic compartment (intraretinal fluid [IRF] volume, subretinal fluid [SRF] volume) status and central subfield ellipsoid zone integrity (mean thickness from the ellipsoid zone to the retinal pigment epithelium [EZ-RPE]) using a machine learning-enhanced feature-extraction platform with manual verification.

Moreover, investigators defined ellipsoid zone integrity maintenance as EZ-RPE >20 µm and particular EZ attenuation as >0 µm to ≤20 µm. The total attenuation was defined as 0 µm.

Intraretinal fluid and subretinal fluid volatility were calculated as the volumetric standard deviation (SD) from Week 12 - 48 of the study. Using ETDRS letters, the BCVA was determined at Week 48 based on the presence or absence of fluid, underlying central subfield ellipsoid zone integrity, and retinal fluid volatility.

The results show the best BCVA outcomes were achieved in eyes without fluid and the maintenance of ellipsoid zone integrity (78 letters). Investigators noted this was significantly improved compared to eyes with subretinal fluid (68 letters; 

In eyes without fluid, those with partial ellipsoid zone attenuation had a BCVA of 67 letters. Eyes with intraretinal fluid (61 letters) had lower BCVA compared to eyes without fluid (70 letters; 

 <.0001).  The worst visual acuity outcomes were observed in eyes without fluid with total ellipsoid zone attenuation (56 letters).

Further, among eyes with subretinal fluid, low volatility (SD ≤Q1) had greater BCVA than eyes with high volatility ([SD ≥Q3] 72 versus 63 letters; 

 = .04). There was no difference found between eyes with low and high intraretinal fluid volatility among eyes with intraretinal fluid (60 vs 58 letters, 

Ehlers noted that if subretinal fluid is persistent, a better understanding of the volatility of the subretinal fluid may be important due to the negative impact of high fluctuation on patient outcomes.

“Treatment approaches that minimize volatility should be considered,” he added.

The paper, “Higher Order OCT Feature Assessment of the Impact of Fluid Dynamics on Visual Acuity in Neovascular AMD in a Phase III Clinical Trial: The Importance of Outer Retinal Integrity,” was presented at 

The best overall outcomes were attained in eyes without fluid and ellipsoid zone integrity preservation, investigators said. 

Ellipsoid Zone Integrity a Key Factor for VA in Eyes with nAMD Without Fluid

, Stevens-Johnson Syndrome (SJS) is an often under-recognized and under-addressed, potentially fatal rare skin condition. In fact, the severe cutaneous drug reaction often falls on the shoulders of dermatologists identifying signs and symptoms and initiating care as soon as possible.

But what is the full SJS care team, and what treatment options are available?

In the second segment of an interview with 

 during the Society of Dermatology Physician Assistants (SDPA) 2022 Annual Meeting, Travis Vandergriff, MD, associate professor in the department of dermatology at UT Southwestern Medical Center, discussed the value of swift progression from diagnosis to care in patients with suspected SJS.

“Days are definitely important,” Vandergriff said. “It can progress very quickly, and even just 1 or 2 days make a big difference.” Vandergriff advised clinicians always check back on uncertain patients within a day of initial symptoms, and to be sure to monitor for changes in appearance at the site of scarring.

Vandergriff additionally discussed the roles of the unique cross-specialty care team involved with SJS, including ophthalmologists, urologists, and gynecologists—teams that he stressed his team at UT Southwestern always utilize for follow-up evaluations at least.

“All SJS patients should be evaluated by an ophthalmologist, and that’s looking for eye involvement, and that could lead to scarring,” he explained. “It may not be clinically obvious that there’s inflammation in the eye, but they can detect that through an eye exam.”

Regarding urologists and gynecologists, Vandergriff stressed the risk of erosion in the mucosal parts of the genital and urinary systems. It could require topical treatments or post-recovery monitoring for strictures and scarring.

“Those 2 teams are really important to consult and involve, during the acute process and then to follow up with afterwards and ensure there is no long-term sequelae or scarring in the affected areas,” he said.

On the subject of long-term outpatient care, Vandergriff said the timeline depends on patient risk factors, comorbidities, and total surface area impacted by the disease. Some patients who survive may be following up with specialists for 6-plus months.

He also discussed the current state of research into potential value of immunotherapies versus standard care for patients with SJS, and the significance of clinicians contributing data toward necessary clinical trials.

“The 2 biggest points to make would be is to recognize the early presentation, and I think that’s an opportunity for education, and then no. 2 is to really pursue the clinical trials that are just beginning to find the best treatment protocols,” Vandergriff said.

Society of Dermatology Physician Assistants

Travis Vandergriff, MD, discusses the unique collaboration with ophthalmologists and urologists in the rare skin condition.

The Adequate Evaluation Teams, Treatment Plans for Stevens-Johnson Syndrome

Tapinarof cream 1% (VTAMA) provides consistent benefit for patients with 

 across a variety of baseline disease severity and demographic factors, according to a new assessment.

In data derived from a pair of pivotal phase 3 trials involving the Dermavant topical therapy, a team of US investigators reported the agent was associated with efficacy and tolerability for patients with differing physician global assessment (PGA) and percentage body surface area (BSA) scores at baseline.

Led by Leon Kircik, MD, founder and medical director of DermResearch and Physicians Skin Care, the team of investigators assessed data from the phase 3 PSOARING 1 and PSOARING 2 clinical trials—from the pivotal program supporting tapinarof cream’s application and acceptance for use in treating psoriasis from the US Food and Drug Administration (FDA).

The supporting findings from the PSOARING program were “unheard of in a topical medicine” prior to tapinarof, Dermavant chief executive officer Todd Zavodnick told 

“When you talk about remittance and staying clear for that time, you're always talking about injectable medicine,” 

. “And we're talking about a topical, that's going to allow cost control within a category and the ability to move from steroids to nonsteroidals.”

PSOARING 1 and 2 showed a once-daily regimen of the topical cream provided statistically significant benefit at 12 weeks versus vehicle in adults with mild to severe plaque psoriasis. Kircik and colleagues sought results for the trials’ primary efficacy endpoint of PGA response by scores of 0 or 1, or ≥2-grade improvement from baseline to week 12, based on baseline characteristics including PGA score, BSA, and duration of disease. They additionally sought efficacy data based on patient sex, age, race and country of enrollment—either US or Canada.

Patients with baseline PGA scores of ≥2 and BSA involvement ≥3 to ≥20% had been randomized 2:1 to tapinarof cream 1% or vehicle treatment for 12 weeks. The pooled analysis from Kircik and colleagues included 683 patients on therapy and 342 control patients.

A majority (82%) of patients had a PGA score of 3, indicating moderate disease, psoriasis for >10 years (57%), were male (57%), aged <65 years old (86%), White (85%), and enrolled in the US (76%). Just 26% had BSA ≥10% at baseline.

Investigators observed a PGA response outcome of 38.6% among treated patients versus 9.3% in vehicle among patients with baseline BSA <10%. PGA response outcome was observed in 35.6% of treated patients with baseline BSA ≥10% versus 9.3% of patients on vehicle.

PGA response was met by 34.8% of patients on tapinarof versus 7.8% on vehicle among those with <5 year disease duration. Such outcomes were 36.9% and 4.1%, respectively, among patients with baseline disease duration of 5-10 years, and 39.3% and 6.5%, respectively, among patients with baseline duration of >10 years.

Kircik and colleagues additionally observed a consistent PGA response among patients treated with tapinarof cream versus vehicle across sex, age, race and their country of enrollment.

“Tapinarof cream 1% once-daily was consistently efficacious and well tolerated irrespective of baseline PGA score, BSA affected, duration of psoriasis, sex, age, race and country of enrollment,” investigators concluded, “supporting its use across a broad spectrum of disease severity and patient populations.”

The study, “Tapinarof Cream 1% Once Daily for Plaque Psoriasis: Efficacy by Baseline Disease Characteristics and Demographics in Two Pivotal Phase 3 Trials,” was published online in 

An analysis of PSOARING 1 and 2 data show the topical therapy is efficacious across a wide spectrum of psoriatic disease and patient demographics.

Tapinarof Cream Benefits Psoriasis Regardless of Baseline Disease Severity, Duration

Guselkumab was associated with longer treatment adherence and greater proxy remission rates among treated patients with 

 versus those treated with other biologic therapies in a new study.

Findings from a new descriptive analysis show differences in time to discontinuation and remission rates among patients with psoriasis treated with either adalimumab, secukinumab, ixekizumab or guselkumab. The data highlight the need for more consistent treatment plans for patients with the chronic skin condition.

A team led by Timothy Fitzgerald, an investigator with Janssen Scientific Affairs, conducted a database-sourced analysis of long-term psoriasis treatment with either of the 4 identified biologics.

“Given the chronic nature of plaque psoriasis, medication persistence is essential to long-term disease control and, potentially, remission,” investigators wrote. “This analysis described persistence of patients with psoriasis initiated on 4 current biologics as well as rates of remission using a treatment patterns-derived proxy.”

They identified adults with psoriasis initiated on adalimumab, ixekizumab, guselkumab or secukinumab in relevant databases between July 13, 2017 and July 31, 2020.

Index dates were defined as the date of the first claim for an included biologic, while discontinuation was defined as gaps between days of index biologic supply based on ≥1-fold and ≥2-fold increases in frequency of administration per label for each therapy—meaning >60 days for guselkumab or <30 days for adalimumab, ixekizumab, or secukinumab.

Investigators described time to discontinuation through Kaplan-Meier models, and reported the both proportion of patients who re-initiated index therapy after discontinuation and proportion who achieved proxy disease remission after discontinuation. They defined remission as patients having no claims for any psoriasis treatment after the index biologic discontinuation date among those with ≥6 months follow-up.

Their analysis included the following cohorts:

3408 patients on guselkumab (mean age, 47.9 years; 47.1% female)

8017 patients on adalimumab (mean age, 47.4 years; 54.1% female)

6123 patients on secukinumab (mean age, 49.4 years; 54.2% female)

3728 patients on ixekizumab (mean age, 49.1 years; 50.3%).

In the 1-fold gap of administration, median time to discontinuation was as follows in the cohorts:

Fitzgerald and colleagues observed 43.1% of patients re-initiate guselkumab following discontinuation; other rates were 37.2% for adalimumab, 50.8% for secukinumab, and 52.3% for ixekizumab. A greater rate of patients achieved proxy psoriasis remission on guselkumab (11.8%) than adalimumab (9.5%), secukinumab (7.2%), and ixekizumab (6.1%).

In the 2-fold gap, median time to discontinuation was as follows:

Investigators observed 22.9%, 21.1%, 31.9%, and 32.0% treatment re-initiation rates after discontinuation among guselkumab, adalimumab, secukinumab, and ixekizumab cohorts, respectively. Proxy remission was again most significant among patients treated with guselkumab (17.2%) versus adalimumab (12.4%), secukinumab (10.5%), and ixekizumab (9.0%).

“In this descriptive analysis, median time to discontinuation trended longer and proxy remission rate trended higher in patients with psoriasis initiated on guselkumab relative to other biologics,” investigators concluded.

The study, “Long-term Psoriasis Control with Guselkumab, Adalimumab, Secukinumab, or Ixekizumab in the United States,” was published online in 

An analysis suggests patients on the biologic fared better with adherence and outcomes than those on competitors including adalimumab.

Guselkumab Linked to Improved Psoriasis Treatment Continuation, Remission

Although men are known to have higher rates of diabetes and cardiovascular disease (CVD), women with diabetes often have a greater risk profile regarding adverse events. 

A recent presentation given at the 6th Annual Heart in Diabetes meeting, accumulated the known data on these sex differences, from observations on less controlled LDL-C and blood pressure in women to the potential for achieve greater benefit from GLP-1 receptor agonist treatment in women. 

, the presenting author, Erin Michos MD, Division of Cardiology, Johns Hopkins School of Medicine, discussed what these data may mean for women with diabetes and what can be done to address these sex-specific issues.   

This transcription has been edited for clarity.

: Can you provide a summary of your discussion on the sex differences in diabetes impact on atherosclerotic cardiovascular disease (ASCVD) and heart failure and note any key highlights?

At this meeting, I'm talking about sex differences in the risk that diabetes confers in heart failure and ASCVD. While there's a greater prevalence of diabetes in men, diabetes confers a greater relative risk of cardiovascular outcomes in women.

In the risk for myocardial infarction, diabetes confers a fourfold increased risk in women compared to a twofold increase in men. Women at the time of diabetes diagnosis have a higher body mass index (BMI) and they tend to have more cardio metabolic risk factors. They have dyslipidemia, and elevated blood pressure at the time of diabetes diagnosis, which may be why they are at greater risk for cardiovascular complications.

But, the good news is that these novel agents that we have, SGLT2 inhibitors and GLP-1 receptor agonists seem to have equal efficacy in both men and women. Similar glucose control, but also similar reduction in major adverse cardiovascular outcomes. Women benefit equally as men do for these important therapies, so we need to prescribe them for appropriate patients irregardless of sex.

Actually, there's even real world data, not from the trials, but real world data suggesting that GLP-1 receptor agonists may even benefit women even more than men. They can seem to confer greater weight loss in women than in men. With a similar glycemic control, women do tend to have a few more side effects, gastrointestinal side effects with GLP-1’s than men do. But again, most of the time, the side effects can be managed with appropriate counseling and with the GLP-1’s, starting slow and working your way up.

: What is the larger importance of including more women in clinical trials?

It's really, really important because we've shown this and demonstrated this over and over again, that women are underrepresented in cardiovascular clinical trials relative to the disease burden in the population. We examine this for both lipid lowering studies and cardiometabolic studies. And it is true for certain conditions like acute coronary syndrome, the prevalence is less in women than in men.

But if you benchmark enrollment and trials to the burden of disease in the population, women are underrepresented. Historically, only like 25% of trial participants are female. So, you can look for interactions by sex, but if there's not enough women in the trial, you're not going to have enough statistical power to see if there's an effect modification, not only for efficacy, but for safety.

Clinical trials serve as the backbone of how we get FDA approvals and implement these into our guidelines. If we're going to disseminate this in our clinical population, we want to make sure that trial results are representative of the patients we see every day in clinic, so not only women, but we also need to make sure we have adequate enrollment of older adults and adults that come from underrepresented minority, racial ethnic groups.

: How does gestational diabetes play into this conversation?

Unfortunately, gestational diabetes is on the rise both in the United States and globally. It’s kind of mirroring the trends and rise in obesity. Obviously, obesity pre pregnancy is a big risk factor for these adverse pregnancy outcomes, including gestational diabetes.

We have an oral presentation here at Heart in Diabetes being presented by one of my mentees, Dr. Sam Anza. He's a medicine resident at Rochester General. And what we showed in a national sample of over 15 years of delivery hospitalizations was that women with GDM compared to controls had increased risk of acute cardiovascular complications, so they were nearly twofold more likely to have preeclampsia. And they were also at increased risk for having stroke, peripartum cardiomyopathy, and acute kidney injury.

This is really, really important and why we need to try to prevent gestational diabetes in the first place, but also make sure that they're closely followed. But even if we get women through the pregnancy and delivery, that we know that gestational diabetes is associated with a tenfold increased risk of developing type 2 diabetes, and there's a lot of emerging area whether this some of these agents like GLP-1 receptor agonists may potentially be useful in this group.

But not only that, it's associated with a twofold increased risk of developing cardiovascular events and this could be even more 10 years out from their index pregnancy. Even if you look at women who had GDM, but didn't develop interim type 2 diabetes, they still have an elevated risk of developing coronary artery calcium that was shown in the CARDIA study and about a 60% increased risk of a clinical cardiovascular event, even if they're euglycemia after delivery, it'll still have long term complications.

: As a multidisciplinary issue, how does a care team need to be shaped to be able to address these issues?

For women who have had adverse pregnancy outcomes like gestational diabetes, it's really important that they're taken care of by a multidisciplinary team, and postpartum in the fourth trimester, you know that there's this appropriate handoff between OB/GYN to primary care.

Outside of this, one of the conversations we've been having at this meeting is around obesity management. Obviously, obesity is one of the big drivers of diabetes and other comorbidities such as heart failure, particularly heart failure with preserved ejection fraction, atrial fibrillation.

One of the big messages, I think, is that cardiologists need to be in this space of managing diabetes. There’s just not enough obesity medicine specialists, and there's more than double cardiologists and endocrinologists. Because obesity can lead to so many downstream cardiovascular complications cardiologists need to get involved in this space.

We have new agents now, because many patients still struggle with their weight, even after counseling them about diet and lifestyle. You know, obesity is skyrocketing. 42% of US adults are obese and 70% are overweight and obese. Now we have agents like semaglutide, that can confer a 28 pound weight loss at the maximum dose.

Just released was the results from SURMOUNT-1, a trial of tirzepatide. I mean, it's unbelievable, they showed at the highest dose of 50 milligrams, there was a 22% relative weight loss, which translates to 52 pounds. 52 pounds of weight loss with a pharmacological agent is bariatric surgery levels of weight loss, and this should have substantial impact on our patients, preventing these long term comorbidities that we see from obesity.

I think cardiologists really need to get involved in obesity medicine management, or at least know how to appropriately refer and counsel their patients about these new therapeutic options.

Erin Michos, MD: Sex Specific Differences in Risk Factor Profiles in Diabetes Care

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