6/28/2016
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`Dymista®: in a class of its own for the treatment of allergic rhinitis- Key Opinions
`
`allergic rhinitis
`jean Bousquet, David Price, Massimo Triggiani, Ludger Klimek
`
`(
`
`[~ACI\
`
`In reality, allergic rhinitis is poorly managed (1-7)
`Although intranasal corticosteroids (INS) are the most effective allergic rhinitis (AR) treatment(8;9l, not all patients
`achieve optimal symptom relief whilst taking them(10l. Treatment practices as in real life and the degree of
`pharmacologic insufficiency in AR have recently been assessed in the UK and Italy. In the UK, a resource utilisation
`survey of 1 000 AR patients in 2011 showed that 70.5% of patients with moderate/severe disease reported using at
`least 2 AR medications (either prescription or over-the-counter) searching for better and faster nasal and ocular
`symptom relief. However, these patients continued to experience both nasal and ocular breakthrough symptoms(2l.
`Another large UK retrospective observational study, looking only at prescription data, revealed that during the 2010
`hayfever season INS monotherapy proved insufficient for approximately one quarter of seasonal AR (SAR) patients
`(25.9%) and nearly half of perennial AR (PAR) patients (43.6%) who visited their doctor(1l. Approximately 1 in 3 AR
`patients (30.7%) who started the season on INS monotherapy required an additional GP visit, some re-consulting 2
`and even 3 times. A shift to multi-therapy prescription was the consequence, which rose from 33.5% for SAR patients
`and 23.1% for PAR patients at season start to approximately 1 in every 2 patients by season end (SAR: 45.3%; PAR:
`52.0%). The Italian survey of 100 GPs, 100 pharmacists and 552 AR patients revealed that the situation is no better
`there(3•7l. Many GPs (49%) and pharmacists (87%) were unaware of the ARIA guidelines, a fact that was evidenced by
`an over-reliance on anti-histamines (GPs: 37%; pharmacists: 56%) regard less of disease severity, a reluctance to
`switch therapy to more effective ones and a high incidence of co-prescribing behaviour (27% of GPsj(3· 6l. Almost half
`of patients were not satisfied with their AR therapy, with 55% of them reporting multiple therapy usage(7l.
`
`There is a clear pharmacologic unmet need in AR. INS provide sub(cid:173)
`optimal control for many of our SAR and PAR patients,
`additional GP visits and encouraging therapy addon (most commonly
`an oral anti-histamine), even though this is not officially recommended
`by ARIA, nor supported by the majority of scientific literature(1t We
`know that patients frequently
`at
`pharmacy, so
`may be unaware what medications their patients are taking.
`a need to simplify rhinitis treatment with a more effective option with
`proven superiority over current firstline therapies, INS and
`antihistamines. [Prof David Price, UK]
`
`is
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`http:/ /keyopi ni ons. i nfo/downl oads/dym ista-class-treatment-ail ergi c-rhinitis/
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`6/28/2016
`
`Dymista®: in a class of its own for the treatment of allergic rhinitis- Key Opinions
`
`gap
`co
`innovation of Dymista® derives from the incorporation of two
`potent drugs from different medication classes with
`complementary effects (i.e. azelastine hydrochloride [AlE] and fluticasone propionate[FP}}, in a
`novel, patented formulation and an improved device. It is considered by myself, and others, as
`the drug of choice for AR(13•7SJ.
`[Prof Massimo Triggiani, Italy]
`
`,.,
`
`Dymista® is indicated for the relief of symptoms of moderate/severe SAR and PAR if monotherapy with either
`intranasal antihistamines or INS is not considered sufficient<16l.
`
`Only Dymista® provides fast and clinically relevant symptom
`relief(14)
`The efficacy of Dymista® versus intranasal AZE and FP has been investigated in moderate/severe SAR patients in
`randomized double blind trials as well in real life studies in more than 6000 patients<13-15;17l. Dymista® was twice as
`effective as either commercially available first-line therapy, in reducing the overall nasal and ocular symptom score
`(rT7SS: reflective total of 7 symptom scores) (Figure 1 )<14l. While this information is necessary for drug registration, it
`is unclear what it means to patients. To that end, Dymista®'s efficacy was assessed in more clinically-relevant ways,
`using a timeto-response sensitivity analysis and by assessing symptom relief according to most bothersome
`symptom (i.e. nasal congestion). Reponse was defined as~ 30, 50, 60, 75 or 90% change from baseline in reflective
`total nasal symptom score (rTNSS). More Dymista® patients achieved each response (up to and including 90%
`response) and days faster than AZE or FP. One in two Dymista® patients (49.1 %) first experienced a 50% reduction in
`their nasal symptoms and did so up to six days earlier than FP (p=0.0284) and AZE (p=0.0223) and up to 10 days
`ahead of placebo (p<0.0001 )(14). A response ceiling of 60% rTNSS was identified, at or above which FP could no
`longer be differentiated from placebo. Dymista® breached this INS response ceiling and did so up to 7 and 8 days
`faster than FP (p=0.0496) and AZE (p=0.0404), respectively. Putting these results into the context of a typical12.5 day
`symptom episode<18l; a similar proportion of patients treated with FP, AZE or PLA achieved a 60% response within this
`SAR episode window (i.e. approx. 20-25% of patients). However, this level had already been achieved by Dymista® on
`Day 5, increasing to 1 in 3 patients by the end of a typical symptom episode (Figure 2). Furthermore, Dymista® was
`three times as effective as FP (p=0.0018) in relieving nasal congestion in congestion-predominant patients and five
`times as effective as AZE (p=0.0001) (Figure 3). FP and AZE were no better than placebo for these patients(1 4l.
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`Dymista®: in a class of its own for the treatment of allergic rhinitis- Key Opinions
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`''
`
`There is a real need to describe response to treatment in way that is
`relevant to both patients and physicians. Patients simply would like to
`know how quickly they will fe el better, while physicians would like to
`explain the
`of improvement their patients may expect from a
`new treatment compared to the treatment they are
`using,
`and also whether it will be effective for afl'patient types,'
`those
`patients who present with the most bothersome symptom of
`congestion. The efficacy of
`has been assessed in a way which
`answers
`bridging
`trial results,
`expectations.
`physician understanding and
`responder analysis tells patients that
`they may expect to feel a substantial response on Dymista® almost a week faster than on an
`INS or antihistamine. Crucially for physicians, the responder analysis defines the level of
`response NOT achievable by currently considered first-lineAR treatments (i.e. <:::60% rTNSS
`response). This newly identified INS efficacy threshold helps to explain symptom breakthrough
`in INS-treated
`may help to
`INS should no
`considered the most effective symptomatic treatment for AR as
`cannot provide
`symptom control in many moderate/severe AR patients. Finally, the predominant symptom
`analysis reassures physicians that they now have
`in their treatment
`which
`can effectively tackle
`most bothersome symptom of congestion more
`than ever
`before. Dymista® will simplify the way we manage AR. It provides the best response, in
`shortest time for more patients and for all patient types. [Prof jean Bousquet, France]
`
`Effectiveness of Dymista® in real life is better than the
`efficacy observed in controlled studies(14;15;17)
`
`The efficacy of Dymista® has been well-established in randomized controlled trials (RCTs), where it was shown to
`provide complete/near-to-complete symptom relief in 1 of 6 moderate/severe SAR patients and in 7 of 10 mild-to(cid:173)
`moderate PAR patients, many days faster than an INSl14;15l. The effectiveness of Dymista® has also been assessed in
`real life in a German, multi-centre, prospective, 14-day (approx.) non-interventional study, including 1781 patients
`with moderate/severe ARl17l. Eligible patients were prescribed Dymista® according to SPC, and evaluated their AR
`symptom severity on a simple 100 mm visual analogue scale (VAS), from 0 mm (not at all bothersome) to 100 mm
`(very bothersome) in the morning prior to Dymista® use and on Days 0, 1, 3, 7 and last day. Patients' perceivecllo""'l
`of disease control was assessed on Day 3. Dymista® reduced the VAS score from 75.4 mm (SD 17.2) at baselinE A
`]
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`Dymista®: in a class of its own for the treatment of allergic rhinitis- Key Opinions
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`response to treatment under usual conditions of care. Randomized
`controlled trials (RCTs) are necessary for drug registration, but their
`strict inclusion and exclusion criteria for entry, mean that patients
`included in them are often not representative of the general
`population. Rea/life studies include a broad patient population, often
`those actively excluded from RCTs (such as smokers and those with co(cid:173)
`morbidities), and a free ecology of care, thus maximising applicability
`of findings to every day practice. The Dymista® non-interventional
`study is important as it used a simple VAS to assess effectiveness, is the first to describe a
`patientreported VAS score
`value for 'well-controlled' disease (i.e. ::> 36 mm) and to show
`that on
`patients shift from uncontrolled to well-controlled
`after just 7 days
`treatment.
`VAS has recently
`proposed by ARIA as the new control language of AR and
`will form
`basis for the new AR
`simplifying the treatment algorithm,
`compliance,
`open
`effective communication between all stakeholders and will
`facilitate tailoring of AR medication to patients' needs. [Prof David Price, UK]
`
`' ' The true test of any new pharmacologic AR treatment is how it
`performs in a real-world setting; whether (or not) it fulfils the
`promise observed in RCTs, and Dymista® certainly lives up to the
`expectations! My patients who received Dymista® reported a rapid
`onset of action a clinically-relevant
`the first day of
`treatment and
`within the first
`few days. The
`was apparent in my
`and PAR patients (and
`with both SAR & PAR), in adolescents, adults and the elderly,
`of symptom severity
`clinic
`was
`sustained for the duration of treatment. My personal experience is
`now confirmed a real life study. Dymista® delivers what AR
`patients want- faster
`more complete symptom control. The vast majority of AR patients
`who visit their physician have moderate/severe
`and have been, or are currently, on
`treatment. Dymista® offers these patients, for the first
`the chance to be completely
`symptom free, the chance to enjoy the 'feeling' of not having AR. Results from controlled clinical
`trials led experts to describe Dymista® as the drug of choice for AR. The results observed in real
`life further endorse this opinion and position Dymista® as the drug
`choice in real life too.
`[Prof
`Klimek, Germany]
`
`References
`1. Price D, Scadding G, Bachert C, Saleh H, Nasser S, Carter Vet al. Intranasal corticosteroid treatment failure
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`allergic rhinitis: assessment of unmet need by measuring shift to multiple therapies. Allergy 2014;69(Suppl
`
`5. Senna GE, Canonica GW, Triggiani M. Allergic rhinitis diagnosis and treatment in Italy: the pharmacist perspective.
`Allergy 2014;69(Suppl 99):A617.
`6. Senna GE, Canonica GW, Triggiani M. Allergic rhinitis diagnosis and treatment in Italy: pharmacist perspective of
`their last patient case. Allergy 2014;69(Suppl 99):A618.
`7. Canonica GW, Triggiani M, Senna GE. Allergic rhinitis diagnosis and treatment in Italy: the patient perspective.
`Allergy 2014;69(Suppl 99):A616.
`8. BrozekJL, Bousquetj, Baena-Cagnani CE, Bonini S, Canonica GW, Casale TB et al. Allergic Rhinitis and its Impact on
`Asthma (ARIA) guidelines: 2010 revision. J Allergy Clin lmmunol 201 0; 126(3):466-76.
`9. Wallace DV, Dykewicz MS, Bernstein Dl, Blessing-Moore J, Cox L, Khan DA et al. The diagnosis and management of
`rhinitis: an updated practice parameter. J Allergy Clin lmmunol 2008; 122(2 Suppi):S1-84.
`10. Bousquet PJ, Demoly P, Devillier P, Mesbah K, Bousquetj. Impact of allergic rhinitis symptoms on quality of life in
`primary care. lnt Arch Allergy lmmunol 2013; 160(4):393-400.
`11. Anolik R. Clinical benefits of combination treatment with mometasone furoate nasal spray and loratadine vs
`monotherapy with mometasone furoate in the treatment of seasonal allergic rhinitis. Ann Allergy Asthma
`lmmunol 2008; 1 00(3):264-71.
`12. Esteitie R, deTineo M, Naclerio RM, Baroody FM. Effect of the addition of montelukast to fluticasone propionate
`for the treatment of perennial allergic rhinitis. Ann Allergy Asthma lmmunol 201 0; 1 05(2):155-61.
`13. Carr W, Bernstein J, Lieberman P, Meltzer E, Bachert C, PriceD et al. A novel intranasal therapy of azelastine with
`fluticasone for the treatment of allergic rhinitis. J Allergy Clin lmmunol 2012; 129(5):1282-9.
`14. Meltzer E, Ratner P, Bachert C, Carr W, Berger W, Canonica GW et al. Clinically relevant effect of a new intranasal
`therapy (MP29-02) in allergic rhinitis assessed by responder analysis. lnt Arch Allergy lmmunol 2013; 161 (4):369-
`77.
`15. PriceD, ShahS, Bhatia S, Bachert C, Berger W, Bousquetj et al. A new therapy (MP29-02) is effective for t he long(cid:173)
`term treatment of chronic rhinitis. J lnvestig Allergol Clin lmmunol 2013; 23(7):495-503.
`16. Dymista summary of product characteristics. https://www.medicines.org.uk/emc/medicine/27579. 2014.
`17. Klimek L, Bachert C, Mosges R, Munzel U, PriceD, Virchow JC et al. Effectiveness of MP29- 02 for the treatment of
`allergic rhinitis in the reallife:results from a non-interventional study. Allergy Asthma Proc. In press. 2014.
`18. Pitman R, Paracha N, Parker C, Acaster S, Bachert C, Bousquetj et al. Episode pattern and healthcare utilisation in
`patients with seasonal allergic rhinitis. Allergy 2012;67(Suppl 96):A885.
`
`topical treatment in
`with rnild to moderate atopic
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`Dymista®: in a class of its own for the treatment of allergic rhinitis- Key Opinions
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`5 r::ragiliti3t der Ep idermis ('174)
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