Jared Kaltwasser

A new study suggests secukinumab (Cosenytx) has a high retention rate among biologic-experienced patients with psoriatic arthritis (PsA) in real-world settings, and also produces minimal serious side effects.

The research is important because previous data on the real-world usage of the recombinant human monoclonal antibody has been scarce. The drug, which targets interleukin-17A, has been approved for the treatment of PsA since 2015 in Europe and 2016 in the United States.

A team of Greek investigators wanted to know specifically how patients with PsA fared on secukinumab if they had already taken a biologic. The investigators enrolled 75 biologic-experienced patients who were treated with secukinumab at 2 university rheumatology clinics between 2016 and 2018. Their findings were 

Most of the patients (76%) were female. The patients had a mean age of 53.9 years, a median disease duration of 6.7 years, and a median treatment duration of 11.1 months with secukinumab.

Forty-eight (64%) patients had previously been exposed to anti-tumor necrosis factor (TNF) agents only. Five patients (7%) had been exposed only to ustekinumab, an IL-12/23 inhibitor. The remaining 22 patients had been exposed to both therapies.

Fifty-three percent of patients in the study received secukinumab in combination with non-biologics; 35% received the biologic along with glucocorticoids.

At baseline, 97% of patients had peripheral arthritis; 42% had axial involvement; 22% had enthesitis; and 12% had dactylitis, the authors reported.

At the end of the study’s follow-up period, peripheral arthritis scores improved, as did patients’ function scores, which were assessed by questionnaire. All patients with dactylitis at baseline saw the symptom resolve, as did 56% of patients with enthesitis at baseline.

Overall, the secukinumab survival rate was 64%, a rate that was not significantly affected by whether the patients were previously exposed to anti-TNFs only, or anti-TNFs and ustekinumab. The serious adverse event rate during follow-up was 4.8/100 patient-years, and the serious infection rate was 1.2/100 patient years.

Corresponding author Dimitrios Vassilopoulos, MD, of Hippokration General Hospital, in Athens, and colleagues said while the drug had performed well in randomized controlled trials (RCTs), a number of important factors made it important to attempt to gather real-world data.

“Our real life patient population had some unique characteristics compared to the RCTs,” Vassilopoulos and colleagues wrote. “This was a biologic-experienced, treatment-resistant population since almost all patients had been previously exposed to anti-TNFs (93%) and ~29% both to anti-TNF and anti-IL12/23 agents. Furthermore, these patients had long-standing, established disease (median: 6.7 years) and were recruited from university referral hospitals.”

One limitation of the study was that it was retrospective, and the authors said it is possible that their data are missing unreported adverse events. The follow-up period was also relatively short, they said.

Still, the overall findings lend evidence to support the idea that secukinumab can be a meaningful solution for this patient population.

“Our findings suggest that SEC [secukinumab] is an efficacious and well-tolerated biologic agent in this multi-resistant, difficult to treat patient group,” they said.

Klavdianou K, Lazarini A, Grivas A, et al. Real Life Efficacy and Safety of Secukinumab in Biologic-Experienced Patients With Psoriatic Arthritis. 

(Lausanne). Published online June 19, 2020. doi:10.3389/fmed.2020.00288

Articles

New real-world data shows 64% of patients with psoriatic arthritis who had previously been on a biologic stayed on secukinumab for the duration of the study.

Secukinumab Has High Retention Rate in Real-World Psoriatic Arthritis Study

A multi-faceted reorganization of sickle cell disease (SCD) treatment at Yale New Haven Hospital led to dramatic drops in inpatient care, emergency department visits, and costs, and led to nearly two-thirds of patients reporting feeling better off as a result of the new treatment paradigm.

The reorganization is outlined in an article in 

The report suggests that one drawback of the program was that even when patients felt more cared for, they were frustrated by what some saw as a lack of shared decision-making.

Corresponding author John D. Roberts, MD, the medical director of Yale’s SCD program, and colleagues wrote that in 2010, despite the hospital’s long-term focus on SCD care and research, the hospital’s SCD program had the highest average length of stay for adults with SCD among Connecticut’s 6 highest-SCD-volume hospitals. Patient complaints were common, and patient advocacy groups had reached out to hospital leadership with concerns.

Against that backdrop, the hospital sought in 2011 decided to redesign its approach. The hospital appointed new leadership and expanded its use of advanced practice professionals (APPs). They also added psychiatry support to the program.

The SCD program was given its own centralized unit in the hospital (previously SCD services were located on different floors). New nursing leadership and staff were recruited to focus specifically on care of adults with SCD, and the inpatient care of these patients was transferred from general medicine attendings to 

Aside from the logistical reorganization, the program’s other emphasis was on rethinking 

. While the program’s leadership said many or most patients would be best able to manage their pain with opioids, they were also aware that a certain percentage of those patients would be susceptible to addiction or the use of opioids for reasons other than pain. That meant providers would need to be vigilant, Roberts and colleagues said, not only about monitoring patients for signs of dependency, but also for monitoring potential biases on the part of staff. The authors noted that most patients with SCD are African-American or Latino.

“Decisions by those in power and patients’ assessments of those decisions may be affected by racial bias and perceptions of racism,” Roberts and colleagues wrote.

One of the most important facets of the program’s pain management strategy was that care would be provided at home whenever possible. Unscheduled acute care visits were to be converted to scheduled visits with providers invested in the patient’s long-term care whenever possible.

When patients required hospitalization, the program called for their care to be directed by their outpatient providers as much as possible.

“When patients remain in the hospital for more than a few days, it is best if an outpatient clinician is consulted and largely permitted to direct inpatient management; the alternative is inconsistent care, which fosters conflict and a tendency to allow patients to lapse into dysfunctional behaviors,” Roberts and colleagues wrote.

The program achieved important milestones. Inpatient days among program participants dropped by 79%. Emergency department visits dropped by 63%, and hospitalizations fell by 53%. At the same time, inpatient visits increased by 31%. In the end, total costs were down by 49%.

Staff at the hospital reported positive reactions to the changes, and a majority of patients said they were better off as a result of the changes. However, Roberts said the patients’ responses were complicated.

“I was a bit surprised that even when patient’s reported that they were better off, they still thought that the process was unfair,” he told 

Roberts and colleagues wrote that the perception of unfairness was likely due to some patients’ desire for more of a shared decision-making model, which Roberts and colleagues said was unlikely to achieve the same results.

“Evidently, even in retrospect, many do not share my perspective that a doctor-directed approach was the only way to get from where we were to where we are now,” he said.

In sharing their story with other hospitals, Roberts and colleagues said a few key components were critical to their success. Those include at-home management when possible, and an outpatient facility specifically devoted to longitudinal care of patients with SCD. It is ideal if the program’s providers all share a similar approach to opioids and pain management, which they said likely requires a small team of outpatient providers. Those outpatient providers should file personalized care plans for patients, so that if the patient ends up in the emergency room, the hospitalists attending to the patient can provide concordant care. If the patient ends up being admitted, the outpatient physician should guide care.

Finally, due to the likelihood that such shifts will require major changes in organization and day-to-day practice, Roberts and colleagues said strong leadership is key to such a reorganization.

“Given the centrality of pain and pain management with opioids to the care of adults living with SCD and the intrinsically subjective nature of that management, creation of an integrated outpatient and inpatient program requires leadership with the authority or persuasiveness to implement change,” they said.

Rousseau R, Weisberg DF, Gorero J, et al. Utilization, financial outcomes and stakeholder perspectives of a re-organized adult sickle cell program. 

. 2020;15(7):e0236360. doi:10.1371/journal.pone.0236360

Yale New Haven Hospital’s reorganization of its sickle cell disease program led patients to report feeling better off and needing fewer hospitalizations. However, the change left some with the disease still feeling unsatisfied.

Reorganization of Sickle Cell Care Leads to Dramatic Drop in Hospitalizations

Ozanimod reduces B and T cells in patients with relapsing 

 (RMS) at levels dependent on dosing, and has differential effects on naive and memory CD4+ and CD8+ T cells and CD19+ B cells, according to a new investigation of the drug’s mechanism of action.

Ozanimod is a sphingosine-1-phosphate (S1P) receptor 1 and 5 modulator and is FDA-approved for the treatment of relapsing forms of MS. In Europe, it is approved for relapsing-remitting MS (RRMS).

Neurology Neuroimmunology & Neuroinflammation

, corresponding author Sarah Harris, PhD, of Bristol Myers Squibb, and colleagues explained their findings from an exploratory analysis of a phase 1 trial of ozanimod. Their goal was to better understand how the drug affects circulating leukocyte subsets in patients with RMS. Bristol Myers Squibb markets ozanimod under the trade name Ziposia.

The phase 1 study referenced in the new report randomized patients to ozanimod hydrochloride in 2 dosage groups, 0.5 mg/d (13 patients) or 1 mg/d (11 patients). All patients were treated for 12 weeks, including a 7-day dosing escalation. The investigators counted circulating leukocyte subsets using flow cytometry on days 28, 56, and 85 and epigenetic cell counting on days 2, 5, 28, 56, and 85.

The authors found that absolute lymphocyte counts dropped in correlation with dosage. At day 85, CD19+ B-cell counts and CD3+ T-cell counts were reduced by >50% in patients receiving the lower dose and >75% in patients with the higher dose. The flow cytometry analysis also showed the higher dosage had the following effects:

Reductions in CD4+ were greater than reductions in CD8+ T cells

Reductions in CD4+ and CD8+ central memory T cells were greater than the reductions in effector memory T cells

Reductions in mean CD4+ and CD8+ naive T cells were ≥90%

Changes in monocytes, natural killer, and natural killer T cells were minimal

Epigenetic cell counting further showed that Th17 cells were reduced at a greater rate than T regulatory cells.

Harris and colleagues said their findings were largely in line with earlier research. As for the lack of an impact on natural killer and natural killer T cells, the authors said the findings could raise the concern that the therapy increases the risk of infection and malignancy in patients taking the therapy.

“However, phase 3 clinical trials of ozanimod showed infection rates that were comparable with patients treated with IM interferon beta-1a, and infrequent serious infections, no serious opportunistic infections, and low (<1%) rates of malignancy among patients with RMS receiving ozanimod,” the authors wrote.

Another important finding of the study was simply that the higher dosage led to meaningful increased effects.

The authors cautioned, however, that their primary goal was to describe the mechanism of action of ozanimod, and thus the study should be seen as exploratory. They said the novel approach of using epigenetic cell-counting in addition to flow cytometry helped to bolster their overall analysis, but said a cross-validation study of epigenetic cell-counting and flow cytometry methods would be worth pursuing.

Harris S, Tran JQ, Southworth H, Spencer CM, Cree BAC, Zamvil SS. Effect of the sphingosine-1-phosphate receptor modulator ozanimod on leukocyte subtypes in relapsing MS. 

 2020;7(5):e839. Published July 31, 2020. doi:10.1212/NXI.0000000000000839

A new analysis offers insights into how ozanimod works in patients with relapsing multiple sclerosis, as well as the impact of higher dosage.



Study Describes Ozanimod’s Mechanism of Action in Relapsing MS

A new analysis of treatment patterns and survival outcomes in white and African American people with 

 (MM) finds the two groups seemed to have equal access to standard-of-care treatment.

The findings contradict some earlier research, which suggested that African American patients had not benefited equally from new therapies.

Corresponding author Sikander Ailawadhi, MD, of Mayo Clinic Florida, and colleagues report on their findings in the journal 

The investigators noted that a previous comparison using the Surveillance Epidemiology and End Results (SEER) registry found 5-year relative survival rates of African Americans with MM improved only marginal after the introduction of autologous stem cell transplantation (SCT) and the development of novel drugs, while at the same time white patients had statistically significant improvement in survival.

 Other studies raised similar concerns, Ailawadhi and colleagues said, prompting them to conduct the new analysis.

The resulting study leverages data from the Connect MM Registry, a multicenter, prospective observational cohort of people in the US who were newly diagnosed with MM. The registry yielded 2,837 patients in total, of whom 397 were African American and 2,440 were white. The first patients were enrolled in 2009 and the cutoff date for the data in the study was August of 2018.

The authors quantified how many patients were given first-line SCT and the duration of post-transplantation maintenance in those who underwent SCT. Other endpoints were first-line triplet therapy, as well as overall survival (OS) and progression-free survival (PFS).

The investigators found 32% of African American and 36% of white patients received first-line SCT. Rates of triplet therapy in first induction were also similar. Among those receiving SCT, triplet use rates were 72% for both African American and white patients. Among those who did not receive SCT, triplet therapy rates were 44% for African American patients and 48% for white patients. Neither race nor transplantation status appeared to play a statistically significant role in whether or not a patient received first-line triplet therapy, the authors said.

Race did not affect OS in patients who did not receive SCT. However, in patients who did receive SCT, African American patients had longer survival compared to white patients (not reached versus 88.2 months).

Ailawadhi and colleagues noted that the African American cohort tended to be younger, but they said that even after adjusting for age, African American SCT patients still had a survival advantage. Another factor could be that African American patients had longer durations of maintenance therapy. The longer length was not statistically significant, they said, but it might have played a role in their superior survival rates.

As for the conflict between their findings and the findings of the SEER study, Ailawadhi said one factor could be that patients in the SEER database are required to be in the database, while those in the Connect MM Registry chose to be enrolled.

“Voluntary participation in a registry (in contrast to the required participation in SEER) might favor the enrollment of better-insured and better-informed patients who are treated by physicians who follow similar practices (e.g., evidence-based medicine), which could lead to more homogenous treatment patterns and help to reduce the treatment disparities that have been observed in population-based studies,” the investigators wrote.

However, the authors also noted that the Connect MM Registry is primarily made up of patients receiving care in the community setting, and thus it offers a better view of real-world practice than studies based only on data from clinical trial settings.

They concluded that their study underscores the importance of taking proactive steps to ensure new therapies are rolled out equally across racial and other lines, and to ensure that survival benefits are shared equally.

Ailawadhi S, Jagannath S, Lee HC, et al. Association between race and treatment patterns and survival outcomes in multiple myeloma: A Connect MM Registry analysis. 

. Published online July 24, 2020. doi:10.1002/cncr.33089

Waxman AJ, Mink PJ, Devesa SS, et al. Racial disparities in incidence and outcome in multiple myeloma: a population-based study. 

. 2010;116(25):5501-5506. doi:10.1182/blood-2010-07-298760

New research suggests white and African American patients have similar rates of access to new treatments for multiple myeloma.

Author | Jared Kaltwasser

Articles

Secukinumab Has High Retention Rate in Real-World Psoriatic Arthritis Study

Reorganization of Sickle Cell Care Leads to Dramatic Drop in Hospitalizations

Study Describes Ozanimod’s Mechanism of Action in Relapsing MS

Analysis Finds White, African American Patients Have Similar Access to Optimal MM Treatments