Participate in Managed Healthcare Executive's annual State of the Industry Survey and you'll be entered for a chance to win 1 of 2 $100 Amazon gift cards! 

State of the Industry Survey 2021

This issue includes our cover story spotlighting the RNA movement.

Take a Look at our November Issue!


Atopic dermatitis (AD), also known as atopic eczema, is a pruritic inflammatory skin disorder.

 It is distinguished by recurrent eczematous lesions with reddened, blistered, crusty or oozing skin; lichenification; and xerosis.

 Although the prevalence of AD in the United States is higher among children (approximately 11%-13%),

 recent estimates indicate that a considerable proportion of adults are affected (about 7%).

The clinical presentation of AD is heterogeneous.

 AD may follow a relapsing-remitting course with acute flares or occur as chronic persistent disease.

 AD can present on any area of the body but most frequently occurs on the inside of the elbows, back of the knees, top of the feet and lower legs.

The pathogenesis of AD is multifaceted, involves epidermal barrier dysfunction and immune system activation and is likely influenced by environmental factors.

 The strongest risk factor for AD is a family history of atopic diseases and especially of AD.

AD is diagnosed based on clinical signs, historical features, morphology and the distribution of skin lesions. Currently, there are no biomarkers for AD.

 Pruritus is a prominent feature of AD and one that contributes to the substantial disease burden borne by patients.

 In one study of 380 adults with moderate to severe AD, most reported daily itching, and approximately 60% indicated that the itching was “unbearable” or “severe.”

Disease severity can be difficult to determine, because the symptoms of AD can fluctuate over time and depend upon bodily location; darker skin can suggest less severe skin involvement, and assessment tools have different severity categories. Similarly, several severity assessment tools require the subjective judgment of patients (e.g., regarding intensity of itch and sleeplessness).

There are four validated tools to measure AD severity; however, two of these are most often used in clinical trials and may require too much time to be of use to healthcare providers: the Scoring Atopic Dermatitis (SCORAD) index and the Eczema Area Severity Index (EASI). The SCORAD composite score is based on the extent and severity of AD and on patient-reported symptoms (pruritus and sleep loss).

 EASI is used to determine the extent and severity of AD and focuses on four body regions (head and neck, the trunk, and the upper and lower extremities).

 The EASI rates four key clinical symptoms of AD: erythema (redness),induration/papulation (thickness), excoriation (e.g., scratching) and lichenification.

Healthcare and economic implications of AD

In the United States, a significant association exists between AD and immune-mediated comorbidities (e.g., ulcerative colitis, pernicious anemia).

 Adults in the United States with AD also have a higher a prevalence of cardiovascular (e.g., heart disease, high blood pressure), psychological (e.g., depression and anxiety) and other chronic conditions than do those without AD.

 Data from the 2013 U.S. National Health and Wellness Survey (NHWS) determined that adults with AD were more than two times more likely to report sleep disorders, depression and/or anxiety than matched controls without AD (

Itch triggers and exacerbates a host of AD symptoms, diminishing quality of life (QOL) for patients with AD.

 A study using a self-administered internet-based questionnaire indicated that adult patients with moderate or severe AD had significantly more trouble sleeping, longer sleep latency, more frequent sleep disturbances and an increased need for over-the-counter (OTC) sleep medications than those with mild AD (

 A population-based study demonstrated that AD is associated with marked QOL impairment for adults in the United States that restricts patients’ lifestyle (51.3%), leads them to avoid social interaction (39.1%) and affects their activities (43.3%).

Healthcare utilization and economic burden of AD

The costs associated with AD in the United States are approximately $7 billion per year (2020 U.S. dollars). Direct costs are approximately $1.7 billion, and indirect costs have been estimated at $1.04 billion. Intangible costs, estimated by patient willingness to pay for symptom relief, are approximately $4.37 billion.

Adults with AD have increased healthcare resource use compared with those without AD, and higher disease severity is associated with greater utilization.

 An analysis of healthcare claims data from three different populations (commercial, Medicare and Medi-Cal) determined that, each year, adults with AD have average numbers of emergency department visits, outpatient visits and pharmacy prescriptions that are significantly greater than those for adults without AD (

 These results are consistent with an analysis of data from the 2013 NHWS, which demonstrated that adults with AD have average numbers of provider visits (

= .004) that are higher than those of matched controls.

Goals in the management of AD include improving skin, minimizing flares and reducing comorbidities and symptom burden (i.e., sleep disorders and itching).

 Interventions aimed at avoiding triggers, improving the skin barrier and reducing inflammation are central to meeting these goals.

As mentioned previously, symptom severity and response to treatment can be measured using validated tools such as the EASI. The validated Investigator Global Assessment for AD (vIGA-AD), frequently used in clinical trials, is another tool to measure treatment efficacy. The vIGA-AD scale is used to measure improvement in clinical signs and has distinct categories (erythema, induration/papulation, lichenification, and oozing and/or crusting) to assess disease severity in AD.

Guidelines for AD suggest a multifaceted approach. Basic nonpharmacologic measures (e.g., bathing, moisturizing and avoiding triggers) are recommended across all severities of AD. Pharmacologic treatment follows a stepwise progression based on disease severity.

Moisturizers are essential in AD to lubricate and soften the skin, reduce water evaporation, and attract and hold water.

 They can decrease the signs and symptoms of AD and reduce inflammation and severity.

 Severe flares or persistent disease may require wet-wrap therapy, whereby a wetted first layer of tubular bandages or gauze is applied over a topical agent, and a dry second layer is used as the outer barrier.

Step-therapy recommendations for AD suggest topical therapies (e.g., topical corticosteroid) when proper skin care and moisturizers no longer suffice for lesion control.

 Topical agents are used to provide symptom management in acute flares and as maintenance therapy in moderate to severe AD. The potency and dose of TCS can be increased based on symptom severity.

 However, long-term daily use of TCSs is not recommended, because it can be associated with systemic adverse effects (e.g., hypothalamic-pituitary-adrenal axis suppression), skin atrophy, telangiectasia, striae, worsening acne and tachyphylaxis. Some of these adverse effects may persist for several months following discontinuation of TCS.

 Topical calcineurin inhibitors (TCIs) (e.g., Elidel, or pimecrolimus cream 1%; or Protopic, or tacrolimus ointment 0.03%, 0.1%) represent a steroid-sparing class of anti-inflammatory agents that can be used for flares or maintenance in moderate to severe AD.

 They are recommended for patients who have not responded to other topical therapies or for whom other topical therapies are not appropriate.

 However, they are generally less effective than midpotency TCSs, their prescription labeling carries a boxed warning about the risk of malignancy and burning or itching may be experienced during early use.

 Eucrisa, or crisaborole ointment 2%, a nonsteroidal anti-inflammatory PDE4 inhibitor, has a favorable safety profile

 but limited efficacy in patients with mild to moderate disease.

Some patients with an insufficient response to topical therapy or severe disease may require phototherapy or treatment with systemic corticosteroids or other systemic immunosuppressants such as cyclosporine A, methotrexate, azathioprine or mycophenolate mofetil.

 Dupixent (dupilumab), a human monoclonal antibody that inhibits interleukin (IL)-4 and IL-13 signaling, is FDA approved for the treatment of patients 6 years and older with moderate to severe AD not adequately controlled with topical prescription therapies or for whom those therapies are not advisable.

 Although Dupixent demonstrates good efficacy, has a favorable safety profile and requires no clinical laboratory monitoring, it takes time to start working, and the subcutaneous route of administration may limit its use.

 Despite the availability of numerous therapeutic options, there remains an unmet need for additional safe and effective medications for patients with AD.

Formulary decision-making and payer considerations

The results of a study using 2015 data from the Truven Health Analytics MarketScan Commercial and Medicare Supplemental databases revealed that utilization of TCSs or TCIs for AD affects pharmacy budget, irrespective of treatment choice.

 There were marked differences in annual prescription costs per patient based on the mechanism of action (TCI versus TCS) and TCS strength.

 With the availability of new agents in recent years and novel therapies under development, formulary decisions in AD will become more complex.

Barriers to safe and effective AD therapy remain high. Access to certain agents is limited, and payers have requirements for changing therapy.

Access to new medications can be a challenge for healthcare providers, and it may depend on the patient’s insurer and prescription drug coverage.

 Additionally, payers may restrict prescriptions for newer agents, such as biologics and small molecules (e.g., Janus kinase, or JAK, inhibitors), to specialists such as dermatologists or allergists, because their use may require a knowledge base greater than primary care physicians can offer.

 Lack of healthcare insurance may also limit a patient’s access to specialists and the newer therapies they may prescribe. Moreover, the cost of newer agents or out-of-pocket costs may limit patient access to the most beneficial therapy.

Step therapy may require physicians to try several regimens before they find one that adequately controls disease.

 This can result in a significant time delay for relief of AD symptoms. For example, payers often require a 30-day trial of topical TCS or TCI therapy before other therapies are considered.

 Payer step-therapy requirements can also restrict access of certain agents, causing a roadblock to the most safe and effective AD therapy for a particular patient.

The affordability of TCSs prompts the off-label prescribing of these agents. However, medium- to high-potency TCSs are not intended for daily, long-term use.

 At the same time, lack of insurance coverage and the cost of TCIs and Dupixent may restrict their use.

 Less expensive options on formulary may not be as effective as newer, albeit costlier, therapeutics. The high cost of newer therapies may necessitate that payers institute prior authorization criteria or other limits on utilization.

Systemic therapy may be necessary for severe disease, especially when it negatively impacts QOL. Older systemic medications are immunosuppressants and nonspecific. They require a high level of monitoring, including blood tests, and carry the risks related to systemic immunosuppression. They are not the best options for long-term treatment.

The landscape in AD therapies is changing. Targeted agents offer improved safety and efficacy profiles and can modify the disease course, quickly resolve symptoms and enable patients to enter a maintenance phase.

 Importantly, new therapies in development for AD address some of the most important symptoms that impact QOL (i.e., itch and sleep disturbances). Emerging systemic therapies for AD include biologics and oral JAK inhibitors. Promising new topical agents such as JAK inhibitors, which inhibit key regulators of pro-inflammatory signals, are in clinical development.

Clinical development of novel targeted agents: JAK pathway

The JAK family includes JAK1, JAK2, JAK3 and tyrosine kinase 2. The JAK-STAT pathway regulates the differentiation of T helper 2 cells. In addition, several cytokines thought to play a role in the pathogenesis of AD (e.g., IL-4, IL-31) utilize the JAK-STAT pathway of signal transduction. The hyperimmune response in AD, specifically the upregulation of IL-4, plays a key role in skin barrier dysfunction. IL-31 is also implicated in the development of AD, as increased production is associated with nerve crosstalk (i.e., the itching sensation) and worsening pruritus.

JAK inhibitors represent a new direction in the treatment of AD. JAK inhibition targets the itch-scratch cycle by quelling sensory neurons and improving the skin barrier by reducing inflammation.

 The inhibitors selectively bind to different JAK proteins

Oral JAK inhibitors under investigation for AD include Olumiant (baricitinib, which binds to JAK1/2) and Rinvoq (upadacitinib) and abrocitinib (which bind to JAK1).

 Concerns about the safety of oral JAK inhibitors approved for other indications (Xeljanz, or tofacitinib; Olumiant; Rinvoq) because of adverse effects such as serious infections, blood vessel disorders and malignancies have resulted in the FDA extending the review period for an AD indication. Of note, the prescribing information for Xeljanz, Olumiant and Rinvoq include boxed warnings regarding serious infections, malignancy and thrombosis; the boxed warning for Xeljanz also includes risk of mortality.

In September 2021, the FDA approved Opzelura (ruxolitinib cream 1.5%) for the short-term and noncontinuous chronic treatment of mild to moderate AD in nonimmunocompromised patients 12 years of age and older with disease not adequately controlled with topical prescription therapies or when those therapies are not advisable. This is the first topical JAK inhibitor approved for this indication.

 Although the prescribing information for Opzelura carries the same boxed warning as that for oral JAK inhibitors, in the TRuE AD1 and TRuE AD2 clinical trials that supported the FDA approval, there were no safety signals attributable to systemic JAK inhibition.

 Safety concerns for this topical agent are not likely to be as great as those for oral JAK inhibitors.

Ruxolitinib cream has a dual mode of action that targets the pruritic and inflammatory effects of AD with direct delivery to the skin.

 The efficacy and safety of ruxolitinib cream in patients at least 12 years old with mild to moderate AD were assessed in the two large, double-blind, vehicle-controlled phase 3 TRuE AD1 and TRuE AD2 trials.

 Patients were required to have AD for at least two years, an Investigator’s Global Assessment (IGA) score of 2 or 3, and 3% to 20% of their body surface area affected. A total of 1,249 patients were randomized (2:2:1) to receive 0.75% ruxolitinib, 1.5% ruxolitinib or vehicle cream twice daily for eight weeks.

 The primary end point for both studies was the percentage of patients achieving IGA treatment success, defined as clear or almost clear skin with at least a two-grade improvement from baseline at week eight.

Significantly more patients given ruxolitinib in TruE-AD 1 and TruE-AD 2 (0.75% ruxolitinib, 50.0% and 39.0%, respectively; and 1.5% ruxolitinib, 53.8% and 51.3%) met the primary end point versus those given vehicle (15.1% and 7.6%, respectively) (

 Ruxolitinib 1.5% cream was associated with a significant reduction in itch by 12 hours, with even greater reductions reported over eight weeks.

 Ruxolitinib cream also had a favorable safety profile.

 The percentage of adverse effects was similar across treatment groups and among both studies. The most common treatment-related adverse effect was application-site burning, which occurred at the highest frequency in the vehicle group. There were no safety signals attributable to systemic JAK inhibition. The long-term safety of ruxolitinib is currently being evaluated in 44-week extension periods for both studies.

In August, the Institute for Clinical and Economic Review issued its final policy recommendations regarding the effectiveness and value of JAK inhibitors and monoclonal antibodies for the treatment of AD. The New England Comparative Effectiveness Public Advisory Council voted 12-1 in favor of ruxolitinib cream for mild to moderate AD compared with topical emollients alone.

Delgocitinib, a pan-JAK inhibitor (JAK1/2/3, TYK2), is approved in Japan as an ointment for AD.

 Two phase 3 trials, DELTA 1 and DELTA 2, are currently enrolling patients with moderate to severe chronic hand eczema.

The efficacy, safety, tolerability and pharmacokinetics of topical ATI-1777, a JAK1/3 inhibitor, were investigated in a phase 2a, multicenter, randomized, double-blind, vehicle-controlled trial of 50 patients with moderate to severe AD.

 The primary efficacy end point was the percent change from baseline in the modified EASI (mEASI) score, which excludes body surfaces not treated in the trial, at week 4.

 ATI-1777 was associated with a 74% reduction in mEASI score compared with vehicle (41%) (

ATI-1777 had a favorable safety profile.The incidence of adverse effects was similar between the two groups. The most common adverse effects in the ATI-1777 group were increased blood creatinine phosphokinase and headache. There were no cases of thrombosis.

AD is associated with considerable clinical and economic burdens. Itching and sleep disturbances are two of the most troubling symptoms that occur with AD, and they have a substantial impact on patients’ QOL. JAK inhibitors represent a new direction in AD therapy. Their mechanism of action directly targets the pruritic and inflammatory effects of AD. Topical JAK inhibitors, such as ruxolitinib cream, may offer these benefits without the systemic effects associated with oral JAK inhibitors.

1. Weidinger S, Beck LA, Bieber T, Kabashima K, Irvine AD. Atopic dermatitis. 

. 2018;4(1):1. doi:10.1038/s41572-018-0001-z

2. Boguniewicz M, Fonacier L, Guttman-Yassky E, Ong PY, Silverberg J, Farrar JR. Atopic dermatitis yardstick: practical recommendations for an evolving therapeutic landscape. 

. 2018;120(1):10-22.e2. doi:10.1016/j.anai.2017.10.039

3. Eichenfield LF, Tom WL, Chamlin SL, et al. Guidelines of care for the management of atopic dermatitis: section 1. diagnosis and assessment of atopic dermatitis. 

. 2014;70(2):338-351. doi:10.1016/j.jaad.2013.10.010

4. Silverberg JI. Public health burden and epidemiology of atopic dermatitis. 

. 2017;35(3):283-289. doi:10.1016/j.det.2017.02.002

5. Silverberg JI, Simpson EL. Associations of childhood eczema severity: a US population-based study. 

. 2014;25(3):107-114. doi:10.1097/DER.0000000000000034

6. Chiesa Fuxench ZC, Block JK, Boguniewicz M, et al. Atopic dermatitis in America study: a cross-sectional study examining the prevalence and disease burden of atopic dermatitis in the US adult population. 

. 2019;139(3):583-590. doi:10.1016/j.jid.2018.08.028

7. Fishbein AB, Silverberg JI, Wilson EJ, Ong PY. Update on atopic dermatitis: diagnosis, severity assessment, and treatment selection. 

. 2020;8(1):91-101. doi:10.1016/j.jaip.2019.06.044

8. Megna M, Napolitano M, Patruno C, et al. Systemic treatment of adult atopic dermatitis: a review. 

 2017;7(1):1-23. doi:10.1007/s13555-016-0170-1

9. Silverberg JI, Margolis DJ, Boguniewicz M, et al. Distribution of atopic dermatitis lesions in United States adults. 

. 2019;33(7):1341-1348. doi:10.1111/jdv.15574

10. Eichenfield LF, Ahluwalia J, Waldman A, Borok J, Udkoff J, Boguniewicz M. Current guidelines for the evaluation and management of atopic dermatitis: a comparison of the Joint Task Force Practice Parameter and American Academy of Dermatology guidelines. 

. 2017;139(4S):S49-S57. doi:10.1016/j.jaci.2017.01.009

11. Simpson EL, Bieber T, Eckert L, et al. Patient burden of moderate to severe atopic dermatitis (AD): insights from a phase 2b clinical trial of dupilumab in adults. 

. 2016;74(3):491-498. doi:10.1016/j.jaad.2015.10.043

12. Institute for Clinical and Economic Review. JAK Inhibitors and Monoclonal Antibodies for the Treatment of Atopic Dermatitis: Effectiveness and Value. Final Evidence Report. August 17, 2021. Accessed September 18, 2021. https://icer.org/wp-content/uploads/2020/12/Atopic-Dermatitis_Final-Evidence-Report_081721.pdf

13. Hanifin JM, Thurston M, Omoto M, Cherill R, Tofte SJ, Graeber M. The eczema area and severity index (EASI): assessment of reliability in atopic dermatitis. EASI Evaluator Group. 

. 2001;10(1):11-8. doi:10.1034/j.1600-0625.2001.100102.x

14. Narla S, Silverberg JI. Association between atopic dermatitis and autoimmune disorders in US adults and children: a cross-sectional study. 

. 2019;80(2):382-389. doi:10.1016/j.jaad.2018.09.025

15. Silverberg JI, Gelfand JM, Margolis DJ, et al. Association of atopic dermatitis with allergic, autoimmune, and cardiovascular comorbidities in US adults. 

. 2018;121(5):604-612.e3. doi:10.1016/j.anai.2018.07.042

16. Eckert L, Gupta S, Amand C, Gadkari A, Mahajan P, Gelfand JM. Impact of atopic dermatitis on health-related quality of life and productivity in adults in the United States: an analysis using the National Health and Wellness Survey. 

. 2017;77(2):274-279.e3. doi:10.1016/j.jaad.2017.04.019

17. Simpson EL, Guttman-Yassky E, Margolis DJ, et al. Association of inadequately controlled disease and disease severity with patient-reported disease burden in adults with atopic dermatitis. 

. 2018;154(8):903-912. doi:10.1001/jamadermatol.2018.1572

18. Silverberg JI, Gelfand JM, Margolis DJ, et al. Patient burden and quality of life in atopic dermatitis in US adults: a population-based cross-sectional study. 

. 2018;121(3):340-347. doi:10.1016/j.anai.2018.07.006

19. Bickers DR, Lim HW, Margolis D, et al; American Academy of Dermatology Association; Society for Investigative Dermatology. The burden of skin diseases: 2004 a joint project of the American Academy of Dermatology Association and the Society for Investigative Dermatology. 

. 2006;55(3):490-500. doi:10.1016/j.jaad.2006.05.048

20. Consumer price index (CPI) for medical care. Health Resources and Services Administration. Updated June 2021. Accessed September 20, 202. https://www.hrsa.gov/get-health-care/affordable/hill-burton/cpi.html

21. CPI Adjustment table 2. Health Resources and Services Administration. Accessed September 27, 2021. https://www.hrsa.gov/sites/default/files/hrsa/get-health-care/affordable/hill-burton/cpitables.pdf

22. Shrestha S, Miao R, Wang L, Chao J, Yuce H, Wei W. Burden of atopic dermatitis in the United States: analysis of healthcare claims data in the commercial, Medicare, and Medi-Cal databases. 

. 2017;34(8):1989-2006. doi:10.1007/s12325-017-0582-z

23. Eckert L, Gupta S, Amand C, Gadkari A, Mahajan P, Gelfand JM. The burden of atopic dermatitis in US adults: health care resource utilization data from the 2013 National Health and Wellness Survey. 

. 2018;78(1):54-61.e1. doi:10.1016/j.jaad.2017.08.002

24. Eichenfield LF, Tom WL, Berger TG, et al. Guidelines of care for the management of atopic dermatitis: section 2. management and treatment of atopic dermatitis with topical therapies. 

. 2014;71(1):116-132. doi:10.1016/j.jaad.2014.03.023

25. Simpson E, Bissonnette R, Eichenfield LF, et al. The validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD): the development and reliability testing of a novel clinical outcome measurement instrument for the severity of atopic dermatitis. 

. 2020;83(3):839-846. doi:10.1016/j.jaad.2020.04.104

26. Sohn A, Frankel A, Patel RV, Goldenberg G. Eczema. 

. 2011;78(5):730-739. doi:10.1002/msj.20289

27. Langan SM, Irvine AD, Weidinger S. Atopic dermatitis. 

. 2020;396(10247):345-360. doi:10.1016/S0140-6736(20)31286-1

28. Dupixent. Prescribing Information. Regeneron Pharmaceuticals Inc; 2021. Accessed September 20, 2021. https://www.regeneron.com/downloads/dupixent_fpi.pdf

29. Davari DR, Nieman EL, McShane DB, Morrell DS. Current perspectives on the systemic management of atopic dermatitis. 

. 2021;14:595-607. doi:10.2147/JAA.S287638

30. Chovatiya R, Paller AS. JAK inhibitors in the treatment of atopic dermatitis.


. Published online August 23, 2021. doi:10.1016/j.jaci.2021.08.009

31. Clark R, Bozkaya D, Levenberg M, Faulkner S, Smith TW, Gerber RA. Topical treatment utilization for patients with atopic dermatitis in the United States, and budget impact analysis of crisaborole ointment, 2. 

. 2018;21(8):770-777. doi:10.1080/13696998.2018.1470520

32. Institute for Clinical and Economic Review. JAK inhibitors and monoclonal antibodies for the treatment of atopic dermatitis: final policy recommendations. August 17, 2021. Accessed September 18, 2021.https://icer.org/wp-content/uploads/2020/12/Atopic-Dermatitis_Policy-Recommendations.pdf

33. Sidbury R, Davis DM, Cohen DE, et al; American Academy of Dermatology. Guidelines of care for the management of atopic dermatitis: section 3. management and treatment with phototherapy and systemic agents. 

. 2014;71(2):327-349. doi:10.1016/j.jaad.2014.03.030

34. Arruda LK, Koplin JJ. Atopic dermatitis: aiming for total disease control. 

. 2021;9(4):1508-1509. doi:10.1016/j.jaip.2021.02.030

35. Hülpüsch C, Weins AB, Traidl-Hoffmann C, Reiger M. A new era of atopic eczema research: advances and highlights. 

. Published online August 18, 2021. doi:10.1111/all.15058

36. Bao L, Zhang H, Chan LS. The involvement of the JAK-STAT signaling pathway in chronic inflammatory skin disease atopic dermatitis. 

. 2013;2(3):e24137. doi:10.4161/jkst.24137

37. Kim BS, Sun K, Papp K, Venturanza M, Nasir A, Kuligowski ME. Effects of ruxolitinib cream on pruritus and quality of life in atopic dermatitis: results from a phase 2, randomized, dose-ranging, vehicle- and active-controlled study. 

. 2020;82(6):1305-1313. doi:10.1016/j.jaad.2020.02.009

38. Xeljanz. Prescribing information. Pfizer Inc; 2020. Accessed September 27, 2021. http://labeling.pfizer.com/ShowLabeling.aspx?id=959

39. Olumiant. Prescribing information. Eli Lilly and Company; 2020. Accessed September 27, 2021. https://uspl.lilly.com/olumiant/olumiant.html#pi

40. Rinvoq. Prescribing information. AbbVie Inc; 2019. Accessed September 27, 2021. https://www.rxabbvie.com/pdf/rinvoq_pi.pdf

41. Ruxolitinib cream approved for short-term treatment of atopic dermatitis. AJMC®. September 22, 2021. Accessed September 27, 2021. https://www.ajmc.com/view/ruxolitinib-cream-approved-for-short-term-treatment-of-atopic-dermatitis

42. Incyte announces U.S. FDA approval of Opzelura (ruxolitinib) cream, a topical JAK inhibitor, for the treatment of atopic dermatitis (AD). Incyte. September 21, 2021. Accessed September 27, 2021. https://investor.incyte.com/press-releases/press-releases/2021/Incyte-Announces-U.S.-FDA-Approval-of-Opzelura-ruxolitinib-Cream-a-Topical-JAK-Inhibitor-for-the-Treatment-of-Atopic-Dermatitis-AD/default.aspx

43. Jakafi. Prescribing information. Incyte Corporation; 2021. Accessed October 4, 2021. https://www.jakafi.com/pdf/prescribing-information.pdf

Articles

Targeting the clinical, economic and payer considerations of atopic dermatitis

The proportion of older Americans who need a liver transplant has sharply increased in recent years, primarily due to the rising number of cases of nonalcoholic steatohepatitis (NASH), a new study found.

As the U.S. population ages, researchers with Inova Health System in Falls Church, Virginia, calculated that more patients aged 65 or older will need a liver transplant than ever before.

The authors of the study presented their findings at 

 held by the American Association for the Study of Liver Diseases November 12-15. Their findings were also published in the journal 

The researchers found that the percentage of liver transplant candidate, ages 65 and older, was 9% from 2002 through 2005 but then soared to almost 1 in 4 (23%) from 2018 to 2020. Thirteen percent of the liver transplant candidates from 2002 to 2005 had NASH. That proportion rose to 39% among 2018-2020 cohort. 

Meanwhile, the percentage of patients with hepatitis C virus (HCV) dropped from 27% to 18% between the two study periods.

Maria Stepanova, Ph.D., senior biostatistician at Inova Health System and the study’s co-author said that older patients who have had liver transplants are now faring better than ever before. Recent data from pilot studies has shown that liver transplants are feasible, AASLD said in a 

“In the past, older patients were routinely denied listing for liver transplantation because doctors believed they were less likely to survive the surgery and post-transplant management,” Stepanova said.

From the late 1960s through the 1980s, a liver transplant recipient’s age could not exceed 45 to 50 years, she noted in the press release. “That age limit gradually increased, but the application of arbitrary age cutoffs for transplant listing remained,” Stepanova said.

“By studying the outcomes of liver transplantation in the elderly, we can provide evidence to support the expansion the transplant candidate pool,” said Zobair Younossi, M.D., president of Inova Health System and the study’s senior investigator. “In fact, we believe it is more about the physiologic age of the patient than their chronologic age.”

While age limits are largely being abandoned as exclusion criteria, the mid- and long-term outcomes of elderly transplant candidates and recipients are still not well understood, according to Stepanova.

Reviewing data on 31,209 liver transplant candidates, the researchers found that older patients had a lower rate of liver transplants and a higher rate of removal from the list due to their condition deteriorating. However, their mortality rates while waitlisted were similar to those of younger candidates.

Factors that predicted a higher chance of liver transplants in older candidates included more recent waitlisting, being male and having a college degree, a higher “model for end-stage liver disease” (MELD) score or hepatocellular carcinoma diagnosis, AASLD said. Being Latino, being on Medicaid or having type 2 diabetes were associated with a lower chance.

Rates of post-LT mortality were higher in older patients than in younger patients.

Researchers found that 33% of the LT candidates had type 2 diabetes, and their mean body mass index was 25±5 kg/m2. Candidates’ Model for End-Stage Liver Disease (MELD) score, which estimates a patient’s chances of surviving over the next three months, was 19±10.

Medical conditions that indicated LT in older candidates varied. Thirty-one percent had NASH, 23% had hepatitis C virus, 18% had alcoholic liver disease, 5% had primary biliary cholangitis., 3% had hepatitis B virus, 3% had autoimmune hepatitis, and 3% had primary sclerosing cholangitis.

In addition to their primary liver disease, 30% of these older candidates also had hepatocellular carcinoma.

More patients aged 65 or older in the United States will need a liver transplant than ever before, according to a study by Inova Health System.

Study: Older Americans Needing Liver Transplants is Spiking

Direct-acting antivirals were effective at reducing the risk of tumor progression in patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC), a new study found.

Researchers at the Osaka City University Graduate School of Medicine in Osaka, Japan, discovered that, after patients received cancer treatment, the oral administration of direct-acting antivirals reduced the risk of tumor progression following recurrence of the liver disease.

. The direct-acting antivirals include Harvoni (ledipasvir and sofosbuvir), Zepatier (elbasvir and grazoprevir), and Mavyret (glecaprevir and pibrentasvir).

“DAA (direct-therapy antivirals) is effective at eradicating the hepatitis C virus, a major risk factor for HCC” said Norifumi Kawada, professor of the Department of Hepatology, in a 

. “While it is deemed low or inconclusive whether DAA therapy helps prevent HCC recurrence, little is known about how the antiviral therapy affects progression of the liver disease after cancer treatment.”

“Usually, cancer cells grow over long periods of time before they can be detected as a tumor,” said Hiroko Ikenaga, first author of the paper and with the Department of Hepatology Osaka City University Graduate School of Medicine. “Our study showed that eliminating the hepatitis C virus with DAA suppresses tumor progression, which we suggest contributes to overall patient survival.”

Several other studies have demonstrated the benefit of using direct-acting antivirals in HCC patients, researchers wrote in a 

 published earlier this year. One study reported a significantly lower probability of liver transplantation linked to improved liver function in patients treated with direct-acting antivirals than in those not treated with them. 

, HCC patients treated with direct-acting antivrals had longer overall survival time than the group that did not receive them. Wei-Chen Lin of Mackay Memorial Hospital and her colleagues noted that it remains controversial whether the hepatitis virus C plays a direct or indirect role in causing. Some mouse models have suggested a direct oncogenic effect of the virus. But it is also possible that the virus has an upstream role, causing chronic inflammation and 

Decisions about direct-acting antiviral treatment in HCC patients should be considered in light of the tumor stage, liver function, life expectancy, and patient preferences, the researchers said, and the optimal timing of HCV treatment in patients with HCC is debatable.

“Patients who have undergone potentially curative HCC management would not benefit from delayed DAA therapy. The AGA (American Gastroenterological Association) advises that the best timing for DAA therapy is 4 to 6 months after a complete response to HCC therapy,” they wrote.

Whether the hepatitis C virus plays a direct role in causing hepatocellular carcinoma or an indirect one by fomenting inflammation and cirrhosis is unclear.

Targeting the clinical, economic and payer considerations of atopic dermatitis

Study: Older Americans Needing Liver Transplants is Spiking

Antivirals Reduce Liver Disease Progression in Hepatitis C patients

How Bacterial and Viral Infections Affect COPD Inflammation

Economic, Sociodemographic Factors Affect COPD Hospitalization Readmission

Featured Content

State of the Industry Survey 2021

Take a Look at our November Issue!