persistent disease activity may have significantpersistent disease activity may have significant...

Persistent disease activity may have significant implications for your SLE patients’ life journey.1,2

Is it time to increase the focus on disease activity reduction?

Date of preparation: May 2014Zinc job number: IIIDF/BEL/0053/14

BENLYSTA® ▼ (belimumab) is indicated as add-on therapy in adult patients with active, autoantibody-positive systemic lupus erythematosus (SLE) with a high degree of disease activity (e.g., positive anti-dsDNA and low complement) despite standard therapy.3

References1. Urowitz MB et al. Arthritis Care Res. 2012; 64: 132-137.2. Lopez R et al. Rheumatology 2012; 51: 491-498. 3. GlaxoSmithKline. BENLYSTA Summary of Product

Characteristics. April 2014.


50% of patients with SLE have organ damage in the first 5 years1,†

Contents


SLE Implications1 EfficacyDisease Activty and Flare Reduction

Corticosteroids

Fatigue

5

Patient Profile2

Patient Identification3 Safety6

Assessment Criteria4 MOA and Dosing7

Benefits8


Persistent disease activity and prolonged corticosteroid exposure can result in ongoing organ damage1,4,*

Consequences of persistent disease activity in SLE5-8,*

Persistent disease activity may be a predictor of disease flares†, and is associated with a higher accrual of damage, lower probability of reaching remission during follow-up, and higher corticosteroid dose.1,7,9-12,†

Adapted from Doria et al. Autoimmun Rev 2014.5

Persistent disease activity

Damage

Drug-related side effect

Reduced work productivity

Further damage

Death

Decreased quality of life

Mood disorders


References

Footnotes

1. Gladman DD et al. J Rheumatol. 2003; 30: 1955-1959.2. Petri M et al. Arthritis Rheum. 2012; 64: 4021-4028.3. Steiman AJ et al. Arthritis Care Res. 2012; 64: 511-518.4. Zahr ZA et al. Lupus 2013; 22: 697-701.5. Doria A et al. Autoimmun Rev. 2014; 2014 Jan 27. pii: S1568-

9972(14)00067-6. doi: 10.1016/j. autrev.2014.01.055. [Epub ahead of print]

6. Nossent J et al. Lupus 2007; 16: 309-317.7. Thamer M et al. J Rheumatol. 2009; 36: 560-564.8. Stoll T et al. Rheumatology 2004; 43: 1039-1044.9. Petri MA et al. Arthritis Rheum. 2013; 65(8): 2143-2153.10. Nossent J et al. Lupus 2010; 19: 949-956.11. Steiman AJ et al. [abstract]. Arthritis Rheum. 2011; 63 Suppl 10: 1388.12. Vila LM et al. Rheumatology 2004; 43: 358-363.

* Data from prospective observational studies of SLE patients with a follow-up time of at least 5 years.1-4,9-11

† In a post hoc analysis, patients with active disease had an increased risk of flare over 1 year.12



Persistent disease activity can start causing damage early in the course of the disease1-4,*


Evidence on prevention of organ damage is limited and no organ protective effect has been demonstrated for BENLYSTA® (belimumab).

Years in Registry YEAR 0

YEAR 1YEAR 2

YEAR 3

YEAR 4

YEAR 5

Adapted from Urowitz MB et al. Arthritis Care Res 2012;64:132-137.5

Patient with SDI >0 (%)

Physicians treating SLE are often faced with the challenge of reducing disease activity while minimising damage from the side effects and toxicity of standard treatments6


References

Footnotes

1. Gladman DD et al. J Rheumatol. 2003; 30: 1955-1959.2. Nossent J et al. Lupus 2010; 19: 949-956.3. Zonana-Nacach A et al. Arthritis Rheum. 2000; 43: 1801-1805.4. Becker-Merok A et al. J Rheumatol. 2006; 33: 1570-1588.5. Urowitz MB et al. Arthritis Care Res. 2012; 64: 132-137.6. Kalunian K et al. Curr Med Res Opin. 2009; 25: 1501-1514.

SDI, SLICC/American College of Rheumatology Damage Index.* Data from prospective observational studies of SLE patients with a

follow-up time of at least 5 years.2-5

† Inception cohort of 298 patients within 15 months of diagnosis of SLE were followed for a minimum of 5 years; disease activity was assessed using the SLE Disease Activity Index 2000 (SLEDAI-2K) and damage was assessed using the SLICC/American College of Rheumatology Damage Index (SDI).1


Despite advancements in SLE care, the disease remains uncontrolled for most patients1

In two recent studies:

97.6%

62.5%

of patients did not achieve remission1,*

had persistent or relapsing disease activity2,*‡

Only 2.4% out of a cohort of 1,613 patients with SLE achieved prolonged remission† for at least 5 years3

Within the first year of disease,145 patients (62.5%) out of a cohort of 200 had persistent or relapsing disease2

Remission may not be an achievable goal for the majority of SLE patients3-4

Low levels of disease activity with minimal doses of steroids have been proposed as an alternative therapeutic target5


References

Footnotes

1. Steiman AJ et al. [abstract]. Arthritis Rheum. 2011; 63 Suppl 10: 1388.2. Nossent J et al. Lupus 2010; 19: 949-956.3. Urowitz MB et al. J Rheumatol. 2005; 32: 1467-1472.4. Steiman AJ et al. J Rheumatol. 2010; 37: 1822-1827. 5. Doria A et al. Autoimmun Rev. 2014; 2014 Jan 27. pii: S1568-

9972(14)00067-6. doi: 10.1016/j. autrev.2014.01.055. [Epub ahead of print]

* Data from prospective observational study of SLE patients with a follow-up times of at least a 5-year period.2-3

† Prolonged remission defined as SLEDAI-2K = 0 (serologically quiescent clinically quiescent (SQCQ)), or = 2 or 4 on the basis of active serology alone (serologically active clinically quiescent (SACQ)) for at least 5 consecutive years, with visits ≤18 months apart, during which time the patients could be taking antimalarials, but not steroids or immunosuppressives.3

‡ An inception cohort of 200 patients with SLE (mean SLEDAI 12.2; mean 6.5 ACR classification criteria) from 14 European centres was followed for up to 5 years in order to describe the current early disease course. SLEDAI scores was used as measure of disease activity; a state of inactive disease measured by Physician’s Global Assessment (PGA) of disease activity.3


Disease activity in SLE may present in different patterns1-5,*

60-85% of SLE patients have either RR or CA courses1-3

Disease Activity

Adapted from Barr SG et al. Arthritis Rheum. 1999; 42:2682-2688; Petri M et al. Lupus. 1999;8(8):685-691; Petri M Rheum Dis Clin North America 2000; 26(2):199-213.2-5

Remission

Relapsing-remitting (RR)

time time time

Chronically-active (CA) Long quiescent


References

Footnotes

1. Nossent J et al. Lupus 2010; 19: 949-956.2. Barr SG et al. Arthritis Rheum. 1999; 42: 2682-2688.3. Nikpour M et al. Arthritis Rheum. 2009; 61: 1152-1158.4. Zen M et al. Clin Exp Rheumatol. 2012; 30(6): 856-863.5. Petri M et al. Lupus 1999; 8(8): 685-691.6. Petri M. Rheum Dis Clin North America. 2000; 26(2): 199-213.

* Data from prospective observational studies of SLE patients with follow-up times of at least 5-year period.1-5


What would your treatment goals be for a patient like Carrie who has persistent disease activity?

Diagnosed with SLE in 2006, after the birth of second child

Felt tired and aching prior to diagnosis

Rheumatologist suspected SLE after fever and several episodes of pleurisy

Had two flares in the first year, after which corticosteroids were increased

Since the increase in corticosteroid dose, has noticed some side effects

Feels her disease is getting worse to the point where she is constantly tired and aching

Note: This is not a real patient and is for illustrative purposes only.

Carrie, 37 year old full-time mum



Clinical Profile And Current Symptoms

• Persistent joint pain, primarily in extremities

• Regular episodes of pleurisy

• No malar rash

• Some signs of kidney involvement

• SELENA-SLEDAI score of 11

Recent Medication History Recent Lab Values




• Chloroquine 400 mg daily since diagnosis

• Triamcinolone (corticosteroid) injections as needed to control joint pain/stiffness

• Currently on methotrexate

• Prednisone dose increased to 7.5 mg/day since last flare






Haemoglobin (g/dL) 10.2

Thrombocytes (x109/L) 260

WBCs (x109/L) 4.1

Creatinine clearance (mL/min) 115

Proteinuria (g/day) 0.4

Immunoglobulins (g/L)

IgA 3.2 IgM 1.4 IgG 16.2

Anti-dsDNA (IU/mL) 40

Complement, C3/C4 (mg/dL) 150/10


Who is the patient with persistent disease activity most likely to benefit from the addition of BENLYSTA®?


BENLYSTA® ▼ (belimumab) is indicated as add-on therapy in adult patients with active, autoantibody-positive systemic lupus erythematosus (SLE) with a high degree of disease activity (e.g., positive anti-dsDNA and low complement) despite standard therapy.1

References1. GlaxoSmithKline. BENLYSTA Summary of Product Characteristics.

April 2014.


Patients likely to benefit from BENLYSTA® can be identified in your clinic

Potential Clinical Manifestations

Appropriate Patients

Treatments BENLYSTA Treatment Goals

Potential clinical manifestations:

• Patients with a wide range of organ domain involvement including those with mucocutaneous, immunological, musculoskeletal, dermal, renal, haematological, vascular, and serosal were studied in the BLISS* trials, and were suitable for treatment with BENLYSTA1-3

• History of recurrent flares1,4,†

• Fatigue1,4,‡


References

Footnotes

1. GlaxoSmithKline. BENLYSTA Summary of Product Characteristics. April 2014.

2. Navarra SV et al. Lancet 2011; 377: 721-731.3. Furie R et al. Arthritis Rheum. 2011; 63(12): 3918-3930.4. van Vollenhoven RF et al. Ann Rheum Dis. 2012; 71: 1343-1349.

* The efficacy of BENLYSTA was evaluated from a pooled analysis of the BLISS trials in the low complement/ anti-dsDNA-positive subgroup (n=876).4

† 39% relative risk reduction in time to severe flare [HR (95% CI) 0.61 (0.44, 0.85); p=0.004 vs. placebo + standard therapy].1,4

‡ FACIT-Fatigue score improvement from baseline at week 52 (least-squares mean), (4.07 vs. 1.80 with placebo + standard therapy (p=0.004).4

§ SRI response rate for BENLYSTA + standard therapy vs. placebo + standard therapy at week 52 was 51.5% vs. 31.7%, p<0.001.4






Appropriate patients should have the following:

Positive antinuclear antibody (ANA) (titre ≥1:80)1,4

AND

Anti-dsDNA autoantibodies (≥30 units/mL)1,2

AND/OR

Low Complement, C3 or C4 (C3<90 mg/dL or C4 <16 mg/dL)1,4


References

Footnotes












Treatments patients are likely to be on, alone or in combination1:

• Anti-malarials

• Long-term corticosteroids or recent corticosteroids ≥7.5 mg/day

• Immunosuppressants


References

Footnotes












Treatment goals in adding BENLYSTA to patients’ current therapy:

Further reduction of SLE disease activity beyond standard therapy1-3,§

Reduction of future severe flares† and fatigue1,4,‡


References

Footnotes








To reduce SLE disease activity,add BENLYSTA® to your patients’ treatment path.

Adding BENLYSTA to standard therapy demonstrated superior disease activity reduction to standard therapy alone.1-3,*

Since 2011, over 16,000 patients worldwide have received BENLYSTA†


References

Footnotes


2. Navarra SV et al. Lancet 2011; 377: 721-731.3. Furie R et al. Arthritis Rheum. 2011; 63(12): 3918-3930.

* The efficacy of BENLYSTA was evaluated in 2 randomised, double-blind, placebo-controlled studies (BLISS-52 and BLISS-76) in 1,684 patients with a clinical diagnosis of SLE according to the American College of Rheumatology classification criteria. Response rate for BENLYSTA + standard therapy vs. placebo + standard therapy at week 52 was 57.6% vs. 43.6%, p=0.0006 for BLISS-52, and 43.2% vs. 33.8%, p=0.021 for BLISS-76.1-3

† March 2011 to November 2013 data sourced from Symphony Health Solutions. Claims data based upon total unique number of patients that have had at least one claim for BENLYSTA. Not all patients remain on therapy with BENLYSTA. Individual results may vary.


BENLYSTA® has been studied in the largest clinical trial programme completed in SLE to date1-3

BENLYSTA was evaluated for disease activity reduction, the occurrence of worsening organ damage and patient condition utilizing the SLE Responder Index (SRI) as the primary endpoint.1-3,*,†,‡,§

Reduction of disease activity was assessed using multiple criteria4,†,‡,§

4 44

434


References

Footnotes


2. Navarra SV et al. Lancet 2011; 377: 721-731.3. Furie R et al. Arthritis Rheum. 2011; 63(12): 3918-3930.4. Furie RA et al. Arthritis Rheum. 2009; 61: 1143-1151.

* SLE Responder Index (SRI), a primary composite endpoint in the BLISS trials, comprised of SELENA-SLEDAI (SS), BILAG domain and PGA scores. 4

† SELENA-SLEDAI (Safety of Estrogens in Lupus Erythematosus: National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index) assesses 24 weighted variables to indicate overall disease severity. 4

‡ BILAG (British Isles Lupus Assessment Group) measures flare activity and severity across 8 organ domains. 4

§ PGA (Physician’s Global Assessment) assesses overall changes in patient condition and disease severity.4


Baseline characteristics of patients with positive anti-dsDNA and low complement1,3

A post hoc analysis found that patients most likely to benefit from the addition of BENLYSTA to their treatment were those with positive anti-dsDNA and low complement, or taking corticosteroids1,3

• Patients with low complement and anti-dsDNA positivity are immunologically active and at high risk of severe flares2

• At baseline, all patients were on tailored standard therapy, including corticosteroids (91.4%) and immunosuppressants (53.4%)3



April 2014.2. Petri M et al. Arthritis Rheum. 2012; 64: 4021-4028.3. van Vollenhoven RF et al. Ann Rheum Dis. 2012; 71: 1343-1349.


If you’re uncomfortable with raising the dosage of standard therapy, it may be time to add BENLYSTA®.


Disease Activity and Severe Flares

The rate and severity of flares are important predictors of disease outcome, and may lead to damage and death.1,2

Flares may also result in higher healthcare costs.3

“I never knew when a bad day would strike...or how bad it would be.”*


References

Footnotes

1. Lopez R et al. Rheumatology 2012; 51: 491-498.2. Ruperto N et al. Lupus 2011; 20: 453-462.3. Doria A et al. Ann Rheum Dis. Published Online First: 20 December

2012 doi:10.1136/ annrheumdis-2012-202443.

* This patient is for illustrative purposes only and is not a real patient.


BENLYSTA® : Superior reduction in disease activity and severe flares in patients with positive anti-dsDNA and low complement1

BENLYSTA + standard therapy demonstrated superior disease activity reduction vs. placebo + standard therapy2,*

0

10

30

40

50

60

20

0 4 8 12 16 20 24 28 32 36 40 44 48 52Visit week

)%( setar rednopser I RS

# # # # # # + # * # * +

51.5%

31.7%

Belimumab 10 mg/kg + standard therapy (n=305)

Placebo + standard therapy (n=287)

19.8% observed difference at 52 weeks1,2,*

Significant improvements in SRI response were seen as early as Week 8 and sustained until Week 76.2

SR

I res

pond

er ra

tes

(%)

*p<0.05; +p<0.01;

#p<0.001


References

Footnotes


2. van Vollenhoven RF et al. Ann Rheum Dis. 2012; 71: 1343-1349.

* BLISS-52 and BLISS-76 pooled data.1,2


BENLYSTA® : Superior reduction in disease activity and severe flares in patients with positive anti-dsDNA and low complement1

BENLYSTA + standard therapy significantly reduced the risk of severe flare vs. placebo + standard therapy2

0

0.1

0.3

0.4

0.2

0 4 8 12 16 20 24 28 32 36 40 44 48 52Visit week

29.6%

19%


Placebo + standard therapy (n=287)HR [95% CI; 0.61 (0.44, 0.85)] vs. placebo + standard therapy

39% relative risk reduction of time to first severe flare2

p=0.004

Pro

babi

lity

of s

ever

e fla

re, H

R (9

5% C

I)


References

Footnotes





Corticosteroids

Escalating corticosteroid use/dose in patients with SLE can be a surrogate marker of disease activity—corticosteroid use being one of the main drivers of late-stage damage accrual in SLE.1

“I was very concerned about my steroid treatment.”*


References

Footnotes

1. Doria A et al. Autoimmun Rev. 2014; 2014 Jan 27. pii: S1568-9972(14)00067-6. doi: 10.1016/j. autrev.2014.01.055. [Epub ahead of print]

* This patient is for illustrative purposes only and is not a real patient.


BENLYSTA®: Changes in corticosteroid dose in patients with positive anti-dsDNA and low complement1,4,*

Prednisone increased to >7.5 mg/day during Weeks 40-524,†

0

10

30

40

50

60

20

0 4 8 12 16 20 24 28 32 36 40 44 48 52Visit week

41.2%

29.1%



Fewer patients with baseline prednisone ≤7.5 mg/day increased their corticosteroid dose with the addition of BENLYSTA.1,4 This was not statistically significant.

Pat

ient

s ex

perie

ncin

g

Pre

dnis

one

incr

ease

(%)

p=0.08


References

Footnotes



* The BLISS studies were not designed specifically to study the effect of BENLYSTA on corticosteroid dose.1-4

† BLISS-52 and BLISS-76 pooled data.1,4


BENLYSTA®: Changes in corticosteroid dose in patients with positive anti-dsDNA and low complement1,4,*

Prednisone reduced to ≤7.5 mg/day in patients during Weeks 40-524,†

0

10

30

40

50

60

20

0 4 8 12 16 20 24 28 32 36 40 44 48 52Visit week

24.6%

15%



More patients with baseline prednisone >7.5 mg/day reduced their corticosteroid dose to 7.5 mg/day or less with the addition of BENLYSTA1,4

Pat

ient

s ex

perie

ncin

g

Pre

dnis

one

incr

ease

(%)

p=0.035


References

Footnotes



* The BLISS studies were not designed specifically to study the effect of BENLYSTA on corticosteroid dose.1-4

† BLISS-52 and BLISS-76 pooled data.1,4


Fatigue

Fatigue is one of the most common and disabling symptoms of SLE and is associated with reduced QoL, pain, poor sleep quality, physical deconditioning, anxiety and depression1-2,†

“If there was one thing I could change, it would be fatigue.”*


References

Footnotes

1. Tench CM et al. Rheumatology 2000; 39: 1249-1254.2. Cleanthous S et al. et al. Lupus 2012; 21: 465-476.

* This patient is for illustrative purposes only and is not a real patient.† Questionaires were used to measure self-reported fatigue, disease

activity, sleep quality, quality of life, anxiety and depression in 120 outpatients with SLE.1


BENLYSTA®: Significant reduction of fatigue in patients with positive anti-dsDNA and low complement1,2

Mean FACIT-Fatigue score improvement from baseline at Week 521,2,*,†

0

1

3

4

5

6

2

0 4 8 12 16 20 24 28 32 36 40 48 52

4.07

1.80

‡

Visit week

+

#

#



Fatigue reduction: 4.5-point improvement in fatigue scores vs. 1.92 with placebo (p=0.0048)

FAC

IT-F

atig

ue s

core

ch

ange

(LS

mea

n)‡

#p<0.001; +p<0.01

Patients saw significant improvement as early as week 8, and it was sustained at week 521,2


References

Footnotes




† FACIT, functional assessment of chronic illness therapy.1,2

‡ LS, least squares.1,2


Rates of adverse events in patients on BENLYSTA® and standard therapy were similar to those on standard therapy alone1-4

Adverse events reported throughout 52/76 weeks2-3

BLISS-52 BLISS-76

Placebo + standard therapy

(n=287)

BENLYSTA 10 mg/kg +

standard therapy (n=290)


(n=275)

BENLYSTA 10 mg/kg + standard

therapy (n=273)

Adverse event (n≥1)

≥1)

≥1)

263 (92%) 266 (92%) 253 (92%) 253 (93%)

Serious adverse event (n 36 (13%) 41 (14%) 54 (20%) 61 (22%)

Severe adverse event (n 34 (12%) 33 (11%) 52 (19%) 54 (20%)

Discontinuation due to adverse events 19 (7%) 15 (5%) 23 (8%) 23 (8%)



April 2014.2. Navarra SV et al. Lancet 2011; 377: 721-731.3. Furie R et al. Arthritis Rheum. 2011; 63(12): 3918-3930.4. van Vollenhoven RF et al. Ann Rheum Dis. 2012; 71: 1343-1349.


Rates of adverse events in patients on BENLYSTA® + standard therapy were similar to those on standard therapy alone1-4

Infections occuring in patients treated with BENLYSTA + standard therapy vs. patients treated with placebo + standard therapy2-3

BLISS-52 BLISS-76


(n=287)

BENLYSTA 10 mg/kg +



(n=275)

BENLYSTA 10 mg/kg + standard

therapy (n=273)

All infections 183 (64%) 194 (67%) 190 (69%) 202 (74%)

≥1 serious infection 17 (6%) 13 (4%) 16 (6%) 20 (7%)

≥1 severe (Grade 3 or 4) infection

9 (3%) 7 (2%) 11 (4%) 7 (3%)

Admission to hospital due to infection 17 (6%) 11 (4%) Data not

availableData not available

Opportunistic infection 0 (0%) 1 (<1%) 0 (0%) 1 (<1%)



April 2014.2. Navarra SV et al. Lancet 2011; 377: 721-731.3. Furie R et al. Arthritis Rheum. 2011; 63(12): 3918-3930.4. van Vollenhoven RF et al. Ann Rheum Dis. 2012; 71: 1343-1349.



Adverse events ≥10% reported in any treatment arm at 52 and 76 weeks2-3

MORTALITY: Out of 2133 patients in 3 clinical trials, a total of 14 deaths occurred in the following groups: 3/675 in placebo, 5/673 in BENLYSTA 1 mg/kg, 0/111 in BENLYSTA 4 mg/kg, and 6/674 in BENLYSTA 10 mg/kg. No single cause of death predominated. Etiologies included infection, cardiovascular disease, and suicide.5

BLISS-52 BLISS-76


(n=287)

BENLYSTA 10 mg/kg +



(n=275)

BENLYSTA 10 mg/kg +


Headache 76 (26%) 66 (23%) 38 (14%) 44 (16%)

Upper respiratory tract infection

47 (16%) 36 (12%) 58 (21%) 54 (20%)

Arthralgia 34 (12%) 33 (11%) 43 (16%) 41 (15%)

Urinary tract infection 25 (9%) 26 (9%) 43 (16%) 44 (16%)

Influenza 25 (9%) 33 (11%) – –

Diarrhoea 20 (7%) 30 (10%) 28 (10%) 33 (12%)

Nasopharyngitis 23 (8%) 20 (7%) 24 (9%) 43 (16%)

Hypertension 30 (10%) 17 (6%) – –

Nausea 31 (11%) 23 (8%) 27 (10%) 46 (17%)

Sinusitis – – 28 (10%) 31 (11%)

Back pain – – 21 (8%) 27 (10%)

Fatigue – – 25 (9%) 21 (8%)

Pyrexia – – 21 (8%) 29 (11%)

Bronchitis – – 21 (8%) 32 (12%)

Insomnia – – 13 (5%) 17 (6%)



April 2014.2. Navarra SV et al. Lancet 2011; 377: 721-731.3. Furie R et al. Arthritis Rheum. 2011; 63(12): 3918-3930.4. van Vollenhoven RF et al. Ann Rheum Dis. 2012; 71: 1343-1349.5. Wallace DJ et al. Lupus 2013; 22(2): 144-154.





BLISS-52 BLISS-76


(n=287)

BENLYSTA 10 mg/kg +



(n=275)

BENLYSTA 10 mg/kg +


Headache 76 (26%) 66 (23%) 38 (14%) 44 (16%)


47 (16%) 36 (12%) 58 (21%) 54 (20%)

Arthralgia 34 (12%) 33 (11%) 43 (16%) 41 (15%)


Influenza 25 (9%) 33 (11%) – –

Diarrhoea 20 (7%) 30 (10%) 28 (10%) 33 (12%)


Hypertension 30 (10%) 17 (6%) – –

Nausea 31 (11%) 23 (8%) 27 (10%) 46 (17%)

Sinusitis – – 28 (10%) 31 (11%)

Back pain – – 21 (8%) 27 (10%)

Fatigue – – 25 (9%) 21 (8%)

Pyrexia – – 21 (8%) 29 (11%)

Bronchitis – – 21 (8%) 32 (12%)

Insomnia – – 13 (5%) 17 (6%)

BLISS-52 BLISS-76


(n=287)

BENLYSTA 10 mg/kg +



(n=275)

BENLYSTA 10 mg/kg +


Headache 76 (26%) 66 (23%) 38 (14%) 44 (16%)


47 (16%) 36 (12%) 58 (21%) 54 (20%)

Arthralgia 34 (12%) 33 (11%) 43 (16%) 41 (15%)


Influenza 25 (9%) 33 (11%) – –

Diarrhoea 20 (7%) 30 (10%) 28 (10%) 33 (12%)


Hypertension 30 (10%) 17 (6%) – –

Nausea 31 (11%) 23 (8%) 27 (10%) 46 (17%)

Sinusitis – – 28 (10%) 31 (11%)

Back pain – – 21 (8%) 27 (10%)

Fatigue – – 25 (9%) 21 (8%)

Pyrexia – – 21 (8%) 29 (11%)

Bronchitis – – 21 (8%) 32 (12%)

Insomnia – – 13 (5%) 17 (6%)


BENLYSTA® selectively targets BLyS, an important factor in SLE1,3-

4

• Patients should remain on therapy for six months before response is assessed.1

3

2

1

Adding BENLYSTA to other treatments may help reduce the abnormal immune system function that contributes to disease activity in SLE1



April 2014.2. Petri MA et al. Arthritis Rheum. 2013; 65(8): 2143-2153.3. Cancro MP et al. J Clin Invest. 2009; 119: 1066-1073.4. Baker KP et al. Arthritis Rheum. 2003; 48(11): 3253-3265.5. Petri M et al. Arthr Rheum. 2008; 58(8): 2453-2459.6. Do RKG et al. J Exp Med. 2000; 192(7): 953-964. 7. Liu et al. Nature Medicine 2012; 18(6): 871-882.



4


3

2

1


Elevated levels of BLyS have been shown to be a predictor of flares and correlate with immunoinflammation in patients with SLE2,5

1



4


3

2

1


BENLYSTA binding to BLyS, allows more B cells, including autoreactive B cells to undergo apoptosis1,3-4,6

2



4


3

2

1


BENLYSTA does not directly bind to B cells and does not directly deplete B-cell populations1,4,7

3


BENLYSTA® schedule for patients with persistently active SLE

BENLYSTA is administered every 4 weeks after the loading phase1

• BENLYSTA is administered as a customised weight-based dose of 10 mg/kg1

• BENLYSTA is administered as a 1-hour IV infusion1

10 mg/kg

Day 0

Required loading phase at 2-week intervals

Day 14 Day 28 One infusionevery 4 weeks after

10 mg/kg 10 mg/kg 10 mg/kg


References

Footnotes


BENLYSTA comes in two vial sizes, 120 mg and 400 mg. BENLYSTA can be administered with concomitant medications.


BENLYSTA® schedule for patients with persistently active SLE

The licensed dose of BENLYSTA is 10 mg/kg

BENLYSTA is given as a one-hour IV infusion on days 0, 14 and 28, and then every 4 weeks


Special considerations before prescribing BENLYSTA®

BENLYSTA has not been studied in the following patient groups, and is not recommended in these situations:

Severe active central nervous system lupus1

Severe active lupus nephritis (i.e. proteinuria >6 g/24 hour or equivalent using spot urine protein to creatinine ratio, or serum creatinine >2.5 mg/dL)1,2

HIV1

History of, or current, hepatitis B or C1

Hypogammaglobulinaemia (IgG <400 mg/dL) or IgA deficiency (IgA <10 mg/dL)1

History of major organ transplant or hematopoietic stem/cell/marrow transplant or renal transplant1

Concomitant use with B-cell targeted therapies or intravenous cyclophosphamide. Caution should be exercised if BENLYSTA is co-administered with other B-cell targeted therapy or cyclophosphamide1



April 2014.2. Dooley MA et al. Lupus 2013; 22: 63-72.


Special considerations before prescribing BENLYSTA®

• Patients treated with BENLYSTA should be made aware of the potential risk of severe or life-threatening hypersensitivity reactions and the potential for delayed onset or recurrence of symptoms. The package leaflet should be provided to the patient each time BENLYSTA is administered.1

• There is a limited amount of data from the use of BENLYSTA in pregnant women, and it should not be used during pregnancy unless clearly necessary.1



April 2014.


Could it be time to consider adding BENLYSTA® instead of more of the same?

Adding BENLYSTA provided significant benefits vs. standard therapy alone in patients with persistent disease activity1,2,*,†

• Superior reductions in SLE disease activity2,‡

- A 39% relative risk reduction of severe flare2,§

- A reduction in corticosteroid dose in patients on ≥7.5 mg/day at baseline2,¶

- An improvement in fatigue scores as early as week 82,¥

• Similar adverse event profile to standard therapy alone1


References

Footnotes



* Defined by low complement and positive anti-dsDNA at baseline.† BLISS-52 and BLISS-76 pooled data. ‡ 51.5% SRI response rate vs. 31.7% with standard therapy + placebo

(p<0.001). § HR (95% CI) 0.61 (0.44, 0.85); p=0.004 vs. placebo + standard

therapy. ¶ ≤7.5 mg/day reduction in 24.6% vs. 15.0% with standard therapy

+ placebo (p=0.035). ¥ FACIT-Fatigue score improvement from baseline at week 52

(least-squares mean) 4.07 vs. 1.80 with placebo + standard therapy (p=0.004).


Prescribing Information for BENLYSTA®

PRESCRIBING INFORMATION: BENLYSTA® ▼ (belimumab) powder for concentrate for solution for infusion 120mg, 400mg.

This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. Refer to Summary of Product Characteristics (SmPC) before prescribing. Benlysta is a human IgG1λ monoclonal antibody specific for soluble human B Lymphocyte Stimulator protein.

Indication: Add-on therapy in adult patients with active, autoantibody-positive systemic lupus erythematosus (SLE) with a high degree of disease activity (e.g. positive anti-dsDNA and low complement) despite standard therapy.

Dosage: Treatment should be initiated and supervised by a qualified physician experienced in the diagnosis and treatment of SLE. Benlysta infusions should be administered by a qualified healthcare professional trained to give infusion therapy. Administration may result in severe or life- threatening hypersensitivity reactions and infusion reactions several hours after the infusion has been administered.



Recurrence of clinically significant reactions after initial appropriate treatment of symptoms has also been observed. Benlysta should be administered in an environment where resources for managing potential hypersensitivity reactions and infusion reactions are immediately available. Patients should remain under clinical supervision for a prolonged period of time (for several hours), following at least the first 2 infusions, taking into account the possibility of a late onset reaction. Patients should be made aware of potential risk of severe or life-threatening hypersensitivity and potential for delayed onset or recurrence of symptoms. The package leaflet should be provided to the patient each time Benlysta is administered. The recommended dose is 10 mg/kg intravenously by infusion over a 1 hour period on Days 0, 14 and 28, and at 4 week intervals thereafter. Infusion rate may be slowed or interrupted if the patient develops an infusion reaction. Discontinue infusion immediately if the patient experiences a potentially life-threatening adverse reaction. Benlysta must be reconstituted and diluted before administration. For instructions, see SmPC. Premedication: An antihistamine, with/without an antipyretic, may be administered. Discontinuation: The patient’s condition should be evaluated continuously. Consider discontinuation if no improvement in disease control after 6 months. Older people (over 65 years): Not recommended unless benefits outweigh risks. Dosage adjustment not required. Renal impairment: Dosage adjustment is not required. Caution in severe impairment.



Hepatic impairment: Dosage adjustment unlikely to be required. Children (under 18 years): No data are available.

Contraindications: Hypersensitivity to belimumab or any excipients.

Warnings and precautions: Not recommended in patients with severe active central nervous system lupus, severe active lupus nephritis, HIV, history of/ current hepatitis B or C, hypogammaglobulinaemia (IgG <400 mg/dl) or IgA deficiency (IgA <10 mg/dl) and patients with a history of major organ transplant or hematopoietic stem/cell/marrow transplant or renal transplant. Caution in patients receiving other B cell targeted therapy or cyclophosphamide and patients with a history of malignancy or who develop malignancy whilst receiving treatment. Administration may result in hypersensitivity reactions and infusion reactions which can be severe, and fatal. In the event of a severe reaction, administration must be interrupted and appropriate medical therapy administered. Risk of hypersensitivity reactions is greatest with the first two infusions; however the risk should be considered for every infusion. Patients with a history of multiple drug allergies or significant hypersensitivity may be at increased risk. Premedication including an antihistamine, with or without antipyretic, may be administered before infusion of Benlysta. There is insufficient knowledge to determine whether premedication could diminish



the frequency or severity of infusion reactions. Patients have been reported to develop symptoms of acute hypersensitivity several hours after the infusion has been administered. Recurrence of clinically significant reactions after initial appropriate treatment of symptoms has also been observed.

Therefore, Benlysta should be administered in an environment where resources for managing such reactions are immediately available. Patients should remain under clinical supervision for a prolonged period of time (for several hours), following at least the first 2 infusions, taking into account the possibility of a late onset reaction. Patients should be advised that hypersensitivity reactions are possible on the day of, or the day after infusion, and be informed of potential signs and symptoms and the possibility of recurrence. Patients should be instructed to seek immediate medical attention if they experience any of these symptoms. The package leaflet should be provided to the patient each time Benlysta is administered. Delayed-type, non-acute hypersensitivity reactions have also been observed and included symptoms such as rash, nausea, fatigue, myalgia, headache, and facial oedema. The mechanism of action of Benlysta could increase the potential risk of infections, including opportunistic infections and may interfere with the response to immunisations. Exercise caution when considering use in patients with chronic infections or a history of recurrent infection. Do not use in patients receiving therapy for chronic infection. Patients who develop an infection while treated with Benlysta should be



monitored closely. Live vaccines should not be given for 30 days before, or concurrently with Benlysta, see SmPC.

Interactions: No interaction studies have been performed.

Pregnancy and lactation: Limited data on use in pregnant women. Not to be used unless clearly necessary. Not known whether Benlysta is excreted in human milk or absorbed after ingestion. Maternal IgG is secreted in breast milk so recommended to either discontinue Benlysta or breast feeding.

Undesirable effects: See SmPC for full details. Very common: Bacterial infections (e.g. bronchitis, cystitis), diarrhoea, nausea. Common: Gastroenteritis viral, pharyngitis, nasopharyngitis, leucopenia, hypersensitivity reactions, depression, insomnia, migraine, pain in extremity, infusion-related reactions, pyrexia. Uncommon: Anaphylactic reaction, angioedema, urticaria, rash. Rare: Delayed-type, non-acute hypersensitivity reactions.

Basic NHS Costs: Available as 120mg and 400mg vials containing white/off-white powder for reconstitution to provide 80mg/ml belimumab. 1 x 120mg vial, £121.50, 1 x 400mg vial, £405.00.



Legal category: POM.

Marketing authorisation numbers: BENLYSTA 120mg EU/1/11/700/001, BENLYSTA 400mg EU/1/11/700/002.

Marketing authorisation holder: Glaxo Group Limited, 980 Great West Road, Brentford, Middlesex, TW8 9GS, UK.

Further information is available from: UK Customer Contact Centre, GlaxoSmithKline, Stockley Park West, Uxbridge, Middlesex UB11 1BT, UK. Freephone: 0800 221 441.

Email: [email protected].

Prescribing information updated: Jan 2014.

Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported to GlaxoSmithKline on 0800 221 441.

Date of preparation: April 2014.


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