Biologic therapy ice breaking in rheumatology Ahmed Yehia Ismaeel, MD, Beni-Suef Anti-TNF Anti-IL6 Anti-CD20 Golimumab, adalimumab, etanercept, certolizumab, infliximab Sarilumab, tocilizumab Rituximab Biosimilars

1. Biologic therapy,
ice-breaking
Ahmed Yehia, MD
Immunology (Allergy & Rheumatology)

3. ‫مبدئيا‬
,
‫أنا‬
‫كنت‬
‫ما‬
‫باحبش‬
‫أذاكر‬
‫بيولوجي‬
.

4. We were suffering
from Dr. Google.
Now, we struggle with
Dr. ChatGPT

5. 2023 marks 25 years since the
approval of the first biologic drug in
rheumatology.
Feldmann, M., Maini, R.N., Soriano, E.R. et al. 25 years of
biologic DMARDs in rheumatology. Nat Rev Rheumatol 19, 761–
766 (2023). https://doi.org/10.1038/s41584-023-01036-x

6. How did biologics change
rheumatology?

7. The introduction of TNF-alpha inhibitors & new-age
drugs had revolutionized RA treatment by restraining the
disease activity & slowing the progression in the last few
decades (Radner & Aletaha).
Radner H, Aletaha D: Anti-TNF in rheumatoid arthritis: an overview . Wien Med Wochenschr. 2015, 165:3-9.
10.1007/s10354-015-0344-y

8. What was the first biologic
drug in rheumatology? Infliximab

9. Biologics
Why?
How to use?
How to manage special situations (pregnancy, lactation,
surgery, elderly, children, comorbidities)?
How to manage failure?
When?
When not?
How to choose?

10. ‫لحظة‬
‫تعارف‬

12. A biologic is a pharmaceutical drug that is
either manufactured, extracted from, or
semi-synthesized from a biologic source.

13. Biologic
DMARDs are
• Highly specific
• Parenterally administered (All biologics
require parenteral administration.)
• Protein based agents

14. Administration route
(Biologics are proteins,
so they cannot be
taken orally.)
• Infliximab
Intravenously
• Adalimumab
Subcutaneously
• Rituximab
• Ustekinumab
• Tocilizumab
• Abatacebt
• Golimumab
• Secukinumab
By either route

15. • Inflammatory
cytokines
• Cytokine receptors
• Inflammatory cells
• cell surface
molecules on
immune cells
Biological agents
attack extracellular targets.

16. Biologics classification
Cytokine-targeted therapies
• TNF-α inhibitors: etanercept (ETN), infliximab (INF), adalimumab (ADA), golimumab, certolizumab.
• TNF-α inhibitor biosimilars: ETN-szzs, ETN-ykro, INF-dyyb, INF-abba, INF-qbtx, ADA-atto, ADA-abdm, ADA-adaz.
• IL-1 inhibitors: anakinra, rilonacept, canakinumab.
• Anti-IL-5: mepolizumab. Anti-IL-5 receptor: benralizumab.
• Anti-IL-6 receptor: tocilizumab, sarilumab. Anti-IL-6: siltuximab.
• Anti-IL-12/IL-23: ustekinumab.
• Anti-IL-17A: secukinumab, ixekizumab. Anti-IL-17 receptor: brodalumab.
• Anti-IL-23: guselkumab, tildrakizumab, risankizumab.
B-cell-targeted therapies
• Rituximab (RTX, anti-CD20),ocrelizumab (anti-CD20)
• B-cell growth factor inhibitors: belimumab (anti-Blys).
T-cell-targeted therapies:
• Costimulatory molecule inhibitors: abatacept (anti-CD80/86).
Complement-targeted therapies
• Eculizumab (anti-C5).

19. • Many of the drugs used by
clinicians, even if effective & safe,
were discovered empirically,
meaning their molecular target
was not necessarily known in
advance.
• By comparison, therapeutic
agents derived from biologic
molecules & other targeted
therapies have transformed many
areas of medicine over the past 2
decades.

20. A lot of names
(Suffix conveys specific information relating to their
structure)
• cept: receptor drug which prevents a ligand from binding to its receptor (e.g.,
etanercept, abatacept, rilonacept).
• ximab: chimeric monoclonal antibody (e.g., infliximab, rituximab).
• zumab: humanized monoclonal antibody (e.g., certolizumab, tocilizumab,
ixekizumab, eculizumab).
• umab: fully human monoclonal antibody (e.g., adalimumab, golimumab,
belimumab, ustekinumab).
• ra: receptor antagonist (e.g., anakinra).
• -kin: an interleukin-type substance

21. Humanized and chimeric mAbs — mAbs
originally derived from mouse and rat
can be"humanized" to various degrees
using recombinant DNA technologies to
engineer amino acidsubstitutions that
make them more similar to the human
sequence. Several technologies existto
generate fully humanized antibodies.
In principle, the more similar an mAb is
to human sequences shared among
many individuals,the less likely it is to
elicit an immune reaction against the
mAb such as infusion reactions
andreduced efficacy, although these are
not easily predicted.

23. TNFi
armamentarium

25. In late 2021 WHO Nov 2021, an expanded collection
of 4 suffixes was introduced to accommodate the
increasing number of mAbs, to
•decrease sound-alikes
•provide information about
modifications to the immunoglobulin
structure.

26. These suffixes are to be used instead of "mab"
for mAbs developed from 2022 onward.
• "tug" is used for full-length unmodified immunoglobulins that recognize a
single epitope(monospecific)
• "bart" is used for full-length monospecific immunoglobulins with
engineered constantregions or any point mutation introduced by
engineering
• "mig" is used for bispecific or multispecific immunoglobulins with any
structure
• "ment" is used for monospecific immunoglobulin variable region fragments

27. Currently, there are 6 add-on biologics recommended for patients with
asthma.
Currently, there are 6 add-on
biologics recommended for
patients with asthma.

28. It is important to know the mechanism of action & indications.

29. A Behcet disease
patient presents with
anterior uveitis.
How to treat?
Case
Uveitis?!!

31. 2018 update of the EULAR recommendations
for the
management of Behçet’s syndrome

32. Systemic immunosuppressives
could be considered for those
with poor prognostic factors
such as young age, male sex &
early disease onset. (IV D)
Isolated anterior
uveitis

33. A Behcet disease patient
presents with bilateral
panuveitis & sudden
diminution of vision
down to HM.
How to treat?
Case

34. 2018 update of the EULAR recommendations for
the management of BS
Any patient with BS & inflammatory eye
disease affecting the posterior segment
should be on a treatment regime such as
azathioprine (IB), cyclosporine-A (IB),
interferon alpha (IIA) or monoclonal anti-TNF
antibodies (IIA).

35. Systemic glucocorticoids should be
used only in combination with
azathioprine or other systemic
immunosuppressives (IIA).
Patients presenting with an initial or
recurrent episode of acute sight-
threatening uveitis should be treated
with high-dose glucocorticoids, infliximab
or interferon alpha. Intravitreal
glucocorticoid injection is an option in
patients with unilateral exacerbation as
an adjunct to systemic treatment.

36. Cases message: When to use biologics?
IN SEVERE DISEASES AFTER FAILURE OF
CONVENTIONAL THERAPIES

37. Make sure that
punishment fits the
crime.
Anterior
uveitis
Topical
steroids

38. ‫تعطي‬ ‫ليه‬
systemic
‫تكتب‬ ‫ممكن‬ ‫لما‬
topical
‫؟‬
!!

39. Group for Research &
Assessment of Psoriasis &
Psoriatic Arthritis
(GRAPPA):
updated treatment
recommendations for
psoriatic arthritis 2021

40. If the cause is unknown
This is autoimmune.
Give the patient cortisone.
The common
rule.
Dear immunologist,
for your kind care.

41. Dear immunologist, kindly
assess this patient with right
uveitis.
Please, send
me more
details.

42. Acute, chronic
or recurrent?
Unilateral or
bilateral?
Anterior,
intermediate,
posterior or
panuveitis?
Granulomatous
or non?

43. Pattern recognition
Ocular
Extraocular

44. The primary parameters used
to characterize uveitis subsets
• Anatomic location of inflammation: anterior, intermediate,
posterior, or panuveitis.
• Laterality: unilateral (can be asynchronous) or bilateral
(occurring in both eyes simultaneously).
• Onset: sudden or insidious.
• Duration: limited (≤3 months) or persistent (>3 months).
• Course: acute (sudden onset & limited duration), chronic
(persistent disease with relapse within 3 months of
discontinuation of therapy), recurrent (repeat episodes
separated by ≥3 months).

45. Case: This patient
has bilateral
granulomatous
panuveitis.
D.D.
Workup

46. HRCT findings
(A: Ground glass opacity,
B: Micronodule,
C: Nodule,
D: Consolidation).
Serum ACE: elevated
Sarcoidosis

47. No
improvement
No
improvement
No
improvement

48. The patient’s lung & eye worsened despite
progressive treatment?
• Tuberculin skin test

49. Granulomatous uveitis
Sarcoidosis Multiple sclerosis
Vogt-Koyanagi-
Harada disease
Sympathetic
ophthalmia
Lymphoma
Blau syndrome Histiocytosis
Granuloma
annulare
Lens-induced
Drug-induced:
brimonidine &
pembrolizumab
Idiopathic (as
multifocal
choroiditis)
Common variable
immune deficiency
Juvenile idiopathic
arthritis
High-density
silicone oil
tamponade
Intraocular foreign
bodies including
caterpillar hair
Tattoo-associated
granulomatous
uveitis

50. Granulomatous uveitis (Infectious Causes)
Tuberculosis
Syphilis
Herpes viruses
Cytomegalovirus
Lyme disease
Toxoplasmosis
Toxocariasis
Trematodes
Propionibacterium acnes
Post-streptococcal infections
Some fungal infections including following coronavirus disease-2019: candida, histoplasmosis, and cryptococcosis

51. How to Prepare
the patient
before biologic
therapy?

54. •HCV
•HBV
•TB
Screen
for

55. A multidisciplinary expert panel, the Italian
multidisciplinary task force for screening of
tuberculosis before and during biologic therapy
(SAFEBIO)

56. •Increased risk of tuberculosis (TB)
reactivation in patients with latent
tuberculosis infection (LTBI) has
been recorded for anti-TNF
agents, while a low or absent
risk is associated with the non-
anti-TNF targeted biologics.

57. • A multidisciplinary expert panel, the Italian
multidisciplinary task force for screening of
tuberculosis before and during biologic
therapy (SAFEBIO), was constituted, and
through a review of the literature, an
evidence-based guidance for LTBI detection,
identification of the individualized level of
risk of TB reactivation, and practical
management of patients with TB occurrence
was formulated.

58. The literature review confirmed
that TB risk associated with
•
Higher risk
monoclonal anti-TNF agents
•
Low risk
soluble receptor etanercept
•
Low or absent risk
Non-anti-TNF targeted biologics

59. • The majority of recommendations/guidelines
for LTBI screening have been prompted for
patients to be treated with the oldest anti-
TNFα, namely IFX, ETN and ADA, while
no policy document is available for the more
recently marketed biologics such as GOL,
CTP, TCZ, RTX, ABA, and UTK.

60. BCG-unvaccinated
TST & IGRA
Both negative
Annual screening with
TST &/or IGRA if high
risk of TB exposure
TST &/or IGRA positive
Active TB diagnosis
Active TB treatment
Active TB excluded
Prophylaxis for LTBI
BCG-vaccinated
IGRA
IGRA negative
Annual screening with IGRA if
high risk of TB exposure
IGRA positive

61. The panel recommends the use of the IGRA over the TST in
patients who had previously received a BCG vaccination, due to
the high false positive test rates for TST.
Due to the discrepancies between TST & IGRA results & the
recent data on the better performance of combined TST & IGRAs
in the detection of LTBI , in those that are not BCG-vaccinated,
the panel recommends combined use of TST & IGRA as the initial
tests in all patients before starting biologic agents.
Since TST may increase IGRA results, IGRA
determination should precede TST execution.

62. RA, PsA, AS and Pso patients with a positive TST (≥ 5 mm in BCG-unvaccinated) or IGRA (QFT-GIT ≥ 0.35
UI/ml; T-SPOTB when at least one of the antigens has ≥ 6 spots) should have a chest radiograph and, if
suggestive of active TB, a subsequent sputum examination to evaluate the presence of Mycobacterium
tuberculosis .
Patients with RA, PsA, AS and Pso with a negative screening TST or IGRA may not need further evaluation
in the absence of risk factors and/or absence of clinical suspicion for TB in low TB risk countries.
The panel recommends annual testing for LTBI in RA, PsA, AS and Pso patients with a negative screening
TST or IGRA at baseline if they live, travel, or work in situations where TB exposure is likely while they
continue treatment with biologic agents.
After the screening, if the patient results with active TB, the panel recommends appropriate anti-TB
treatment & consideration of referral to a specialist. Oral and written information (education) on TB
infection and disease should be provided to the patient.

63. Treatment
with biologic
agents can be
initiated or
resumed after
1 month of LTBI
treatment with anti-TB
medications
completion of the
treatment of active TB,
as applicable.

64. LTBI treatment
INH for 9 months
INH + RFP for 3 months
RFP for 4 months

65. LTBI patients scored positive to TST or
IGRA at baseline can remain positive
to these tests even after successful TB
preventive therapy.
These patients need monitoring for
clinical signs & symptoms of active TB,
since repeating TST or IGRA will not
help in the diagnosis of TB
reactivation.

66. Host
&
traditional
DMARD-related
TB
risk
reactivation
Host-related Traditional DMARD-related
Demographic characteristic and comorbidity Estimated RR Drug Estimated RR
Age < 50 years 2 Corticosteroids 2.4
Family history of TB 2.38 Methotrexate 3.4
Recent TB infection (< 2 years) 15 Leflunomide 11.7
Former TB disease 2.69
Exposure to active TB subjects 10.1 Cyclosporine 3.8
Cigarette smoker 2 Other (sulphasalazine, azathioprine, hydroxychloroquine) 1.6
Alcohol abuse 1.84
Drug abuse 2.83
Malnutrition, low body weight (BMI ≤ 20) 2
Pso/PsA [24] 3.1
Diabetes 3.11
RA [21] 3.68
AS [25] 3.9
Silicosis 30
Severe kidney disease 25
Abnormal chest x-ray—with upper lobe fibronodular disease typical
of healed TB infection
19

67. SAFEBIO
guidance for
biologic choice in
patients with RA,
PsA, AS & Pso
stratified in
different
categories of TB
risk

68. Panel guidance for the management of RA, PsA,
AS and Pso in patients with active TB complicating
the disease course.

70. Case
A 4-year-old girl presents with 2 months history of
bilateral knee & right wrist arthritis.
What’s the best next step?
Put a D.D. to guide diagnosis plan.

71. D.D. of childhood arthritis.

72. Is this rheumatic fever? ASOT 600  800
Mostly no, duration, echocardiography: normal
Is this JIA?
JIA is a diagnosis of exclusion.
So, we requested ESR, CRP, ANA (IF) with titre, rheumatoid factor,
TSH, calcium, s. 25 OH vitamin D. All were non-significant.

73. Jones criteria for
diagnosis of acute
rheumatic fever

74. ASOT

75. So, this a case of JIA
• Onset: before 16 years of age.
• Duration: manifestations
persist for at least six weeks.
• Exclusion: etiology is unknown.
Per ILAR criteria, JIA is a
diagnosis of exclusion.

76. This is not enough to
make treatment
decision. Which JIA
subtype?
• Persistent
• Extending
Oligoarticular
• RF+ve
• RF-ve
Polyarticular
Systemic onset
Enthesitis-related arthritis (ERA)
Psoriatic arthritis (PsA)
Undifferentiated
ILAR
classification

77. 6 PRINTO JIA categories
•the main modification is that the definition now allows the inclusion of patients with
fever without arthritis, as in the adult equivalent, adult onset Still disease.
Systemic arthritis
•anti-CCP antibodies have been added to the definition
RF positive arthritis
•definition and nomenclature have been made more similar to those of the adult
counterpart
Enthesitis/spondylitis
related JIA
•The major novelty. It has been recognized that this entity, which in the ILAR
classification is split into different categories, represents a homogeneous form of
chronic arthritis, which is typical of children
Early onset ANA+
•Does not fit the disorders a. to d. Arthritis >= 6 weeks.
Other JIA
•Fits more than 1 disorder a. to d. Arthritis >= 6 weeks
Unclassified JIA

79. This is oligoarticular JIA. How will you treat?
• She was initiated on a trial of NSAID with modest response.
• How will you proceed?

80. How to assess
treatment
response?

81. ‫إيه؟‬ ‫البنت‬ ‫مفاصل‬ ‫أخبار‬
‫كويسة‬
.
‫هلل‬ ‫الحمد‬
.

82. ‫إيه؟‬ ‫البنت‬ ‫مفاصل‬ ‫أخبار‬
‫كده‬ ‫أد‬ ‫مش‬
.
‫تانية‬ ‫مرة‬

83. JIA activity assessment?
• Use of validated disease
activity measures is
conditionally recommended to
guide treatment decisions,
especially to facilitate treat-to-
target approaches.
• There is lack of demonstrated
superiority of specific measures.

84. Considered JIA activity
measures
• Wallace preliminary criteria for
Clinical Remission
• ACR provisional criteria for
inactive disease
• Juvenile Arthritis Disease
Activity Score (JADAS)
• Clinical JADAS

85. • The JADAS-CRP & JADAS-ESR
correlate closely, show
similar test characteristics,
and are demonstrated to be
feasible and valid tools to
assess disease activity in all
categories of JIA.

86. Construct & score range of the different
available versions of JADAS
Physician global assessment Parent/patient global assessment Active joint count Acute-phase reactant (range) Score range (total)
JADAS
• JADAS10 0–10-cm VAS 0–10-cm VAS Simple count, 0–10
a
Normalized ESR (0–10)
c
0
–
40
• JADAS27 0–10-cm VAS 0–10-cm VAS Reduced count, 0–27 Normalized ESR (0–10)
c
0
–
57
• JADAS71 0–10-cm VAS 0–10-cm VAS Simple count, 0–71 Normalized ESR (0–10)
c
0
–
101
JADAS-CRP
• JADAS10-CRP 0–10-cm VAS 0–10-cm VAS Simple count, 0–10
a
Normalized CRP (0–10)
b
0
–
40
• JADAS27-CRP 0–10-cm VAS 0–10-cm VAS Reduced count, 0–27 Normalized CRP (0–10)
b
0
–
57
• JADAS71-CRP 0–10-cm VAS 0–10-cm VAS Simple count, 0–71 Normalized CRP (0–10)
b
0
–
101
cJADAS
• cJADAS-10 0–10-cm VAS 0–10-cm VAS Simple count, 0–10
a
– 0
–
30
• cJADAS-27 0–10-cm VAS 0–10-cm VAS Reduced count, 0–27 – 0
–
47
• cJADAS-71 0–10-cm VAS 0–10-cm VAS Simple count, 0–71 – 0
–
91
Consolaro, A., Giancane, G., Schiappapietra, B. et al. Clinical outcome measures in juvenile idiopathic arthritis. Pediatr
Rheumatol 14, 23 (2016). https://doi.org/10.1186/s12969-016-0085-5

87. This is oligoarticular JIA. How will you treat?
• She was initiated on MTX.
• What is the dose?
• Still target is not achieved.

88. This is oligoarticular JIA. How will you treat?

89. Biologic DMARDs
are preferred over
combining
csDMARDs or
switching to a
different csDMARD.
Greater likelihood that bDMARDs will
yield rapid & sustained improvement in
JIA.
While combination csDMARDs have been
used for the treatment of RA in adults, in
children the combination appears to be
less effective & less tolerable.
For these reasons, this recommendation is
strong.

90. There is no preferred bDMARD.
Although TNFi are the most used bDMARDs in
children, other bDMARDs of proven efficacy in
the treatment of JIA may be used.
In the absence of head-to-head trials in children
with oligoarthritis, bDMARD selection may be
driven by specific provider & patient/caregiver
preferences & circumstances, except for IL-1i, which
are preferentially used for the treatment of sJIA

91. She was prescribed
Adalimumab 20 mg
SC/2 weeks.

92. Case
•A 12-year-old female
presents with 3 weeks of
persistent fever &
arthritis.
•Fever is of acute onset &
stationary course of high-
grade fever , constant
through the day not
relieved by antipyretics.

93. • She developed this persistent rash with the fever
onset, which started to fade gradually over the last 3
days.

94. Investigations
•CBC: TLC 20.000, mainly
neutrophils.
•ESR> 100 mm, 1st hour.
•CRP, positive, 24.
•ALT, AST++
•S. ferritin: 2000.
•Hepatosplenomegaly.

95. She was diagnosed as sJIA.
She was initiated on
prednisolone 20 mg daily &
MTX 12.5 mg weekly.
2 weeks later, her fever didn’t
improve with subtle
improvement of arthritis.
Further investigation
revealed:
Blood film: blast cells
30%.

96. sJIA is a diagnosis of exclusion.
• The hallmark of sJIA is the
combination of intermittent but daily
fevers > 38.5ºC (quotidian fever
pattern) & arthritis.
• Rash is evanescent.

97. Fever curve in a patient with sJIA

98. A salmon-pink rash is
characteristic of sJIA.
The rash is brought
out by heat & often
can be found in the
axillae & around the
waist but may be
anywhere.

99. sJIA rash in Panel A, with a
close-up view in Panel B.
The rash usually consists of
multiple round to oval,
salmon-pink macules
slightly raised & of differing
sizes. It can appear
following stroking of the
skin or other minor trauma
(Koebner phenomenon).

100. Case
•A 15-year-old female
with 2 weeks of daily
spiking fever &
evanescent rash
associated with arthritis.

101. Investigations
CBC: TLC 20.000, mainly neutrophils.
ESR> 100 mm, 1st hour.
CRP, positive, 24.
ALT, AST++
S. ferritin: 2000.
Hepatosplenomegaly.

102. A limited work-up for FUO is recommended prior to
treatment to exclude infection, IBD & malignancy.
• Blood & urine cultures
• Radiographs of the chest & affected
bones & joints.
• Obtaining CT of the abdomen & pelvis,
as well as a bone marrow aspiration,
prior to treatment is advised, especially
if a pediatric rheumatologist is
unavailable to confirm the diagnosis.

103. All came negative.
So, we
diagnosed
sJIA.
How to start
treatment?

106. Personalized medicine

107. Case message: No 1 size fits all.
•A good doctor is a good tailor.

108. No 1 biologic
fits all
patients.

110. ‫و‬
‫بالمثال‬
‫يتضح‬
‫المقال‬

111. The Immune System Has 3 Known Types of Responses1,2
Simplified depiction based on key published information; not meant to be exhaustive in nature.
CRSwNP, chronic rhinosinusitis with nasal polyps; IFNγ, interferon gamma; IL, interleukin; ILC, innate lymphoid cell; NK, natural killer; Tfh, follicular helper T cell; TNF, tumor necrosis factor; Th, helper T cell.
1. Haddad EB, et al. Dermatol Ther (Heidelb). 2022;12:1501–1533. 2. Beck LA, et al. JID Innov. 2022;2:100131.
117
Primary immune cells
Key cytokines
Functions
When dysregulated:
Diseases (examples)
Type 1 Type 2
● Antitumor activity
● Cellular immunity: antiviral/antibacterial
● Suppression of type 2 immunity
● Humoral immunity: antiparasitic (helminths)
● Neutralizes toxins
● Regulates wound repair and regeneration
● Suppression of type 1 immunity
Ankylosing spondylitis
Atherosclerosis
Autoimmune gastritis
Diabetes mellitus
Hashimoto thyroiditis
Multiple sclerosis
Rheumatoid arthritis
Sarcoidosis
Atopic dermatitis
Prurigo nodularis
Chronic spontaneous urticaria
Bullous pemphigoid
Allergic rhinitis
Asthma
Chronic rhinosinusitis with nasal polyps
Eosinophilic esophagitis
Macrophage
ILC1
Th1
NK cell Mast cell
Tfh
Th2
Basophil
Eosinophil
ILC2
IL-18
IL-12
IFN
IL-2
TNF
IL-6 IL-5
IL-4 IL-13
IL-31
Type 3
● Regulation of intestinal epithelial barrier
● Responses to extracellular bacteria and
fungi
Ankylosing spondylitis
Multiple sclerosis
Psoriasis
Rheumatoid arthritis
Uveitis
Neutrophil
Th17
ILC3
IL-6
IL-23
IL-22
IL-17
Innate
Adaptive
Innate
Adaptive
Innate
Adaptive

112. Th1 lymphocytes
participate in a broad variety of
inflammatory responses,including
cell-mediated inflammation
RA, PsO, PsA ,acute allograft
rejection, graft-versus-host disease
Interferon gamma (IFNg), TNF, IL 2.
IFNg & IL-2 can inhibit Th2 cell
proliferation.
Th2 lymphocytes
Stimulate antibody production
byB cells & augment eosinophil
responses.
Chronic graft-versus-host
disease, SLE, SSc
IL-4, -5, -10, and -13
IL-4 & IL-10 can inhibit Th1 cytokine production.

113. Th17 cells
Th17 cells differentiate from naive T cells in response
to antigen, transforminggrowth factor (TGF) beta, IL-
6, and IL-23.
Th17 cells secrete a cytokine, IL-17, which in concert
with other cytokines affects inflammation, cartilage,
and bone metabolism
T reg cells
function largely to regulate other T cells. They may
have critical functions in multiple rheumatic diseases,
including GCA, GPA, RA, SLE, SpA, SjS & other
conditions. T reg cells also differentiate under the
influence of antigen & TGF beta & they have a
protective function through IL-10 & TGF beta.
While not yet clinically tested as cell-based therapy,
their capacity to reduceinflammation and
autoimmunity are the subject of interest in this
context.

114. It is important to know the mechanism of action & indications.

115. Endotype: Biological
(molecular) mechanism
Phenotype: Observable
characteristics
(presentation, triggers,
treatment response)
Diabetes
Type 2
Ominous
octat
Insulin
resistance
Type 1
Insulin-
dependent

116. Biological (molecular)
mechanism
Observable characteristics
(presentation, triggers,
treatment response)
Personalized
medicine
Disease
Phenotype
Endotype Endotype
Phenotype
Endotype

119. The major biologic approaches to
treatment of the rheumatologic
diseases include agents that
Interfere with
cytokine
function
01
Inhibit the
"second signal"
required for T-
cell activation
02
Deplete B cells
03

121. summarized flowchart of biologics & cytokines

122. AS case: revise dx if bDMARD fails.

123. What is next? Use of an add-on biologic agent
considered.
Why do we need biologics?

124. There are a lot of Limitations
in Conventional Therapies.

125. Add-On Biologic
Treatment Options

126. Uveitis
AxSPA has a lot of
comorbidities.
IBD Pso

127. Asthma
PsA has a lot of
domains.
AD

128. ‫الحجر‬ ‫يكون‬ ‫لما‬ ‫بالذات‬
‫الجنيهات‬ ‫بآالف‬ ‫بيولوجي‬
.

129. ‫ده؟‬ ‫العمق‬ ‫كل‬ ‫ليه‬

132. • Infection rates are increased with TNF-α
blockers, particularly in the first few
months of treatment, but the rate then
declines.
• There is a known association between RA
and non-Hodgkin’s lymphoma (NHL)
but, overall, registers have not shown an
increased risk of NHL in patients with
RA treated with TNF-α blockers, to date.
There is no convincing evidence of any
increased risk of other cancers.
Reactivation of old tuberculosis may
occur but is probably less common with
etanercept.

134. Putting a maneuver in
unsuitable situation
underestimates its efficacy.

136. •TNFinhibitors are generally well tolerated; increased risk
• for infection is the primary safety concern. Because TNF inhibitors
pose a particul:rrly high risk for reactivation of tuberculosis, all
patients being considered for treatment must be screened for latent
infection and, if needed, receive treatment. Except for nonmelanoma skin
cancer and possibly melanoma, TNF inhibitors do not appear to increase
the risk for
• new cancers; the risk for malignant recurrence remains unclear.
TNFinhibitors may exacerbate heart failure and rarely provoke a
demyelinating condition. Over time, individual TNF inhibitors may lose
efficacy owing to formation of antidrug antibodies.

137. How to manage some special
situations?

138. •A Behcet syndrome lady
developed bilateral
panuveitis flare in the first
trimester of pregnancy
with marked diminution of
vision.

141. • She received prednisolone 40 mg
daily, azathioprine 50 mg twice
daily.
• But her eye condition showed
further deterioration.

143. Another
challenge!!
Her husband

144. Biosimilar definition
by the WHO
•"biotherapeutic product which is
similar in terms of quality, safety, &
efficacy to an already licensed
reference biotherapeutic product".
•"Similarity" is defined as the "absence
of a relevant difference in the
parameter of interest."

145. • Biosimilar agents are "copycat" versions of brand name biologic medications. The drugs are not
exact replicas (hence the term "biosimilar"); therefore, they must undergo phase III testing to prove
equivalent efficacy to the parent biologic.

146. •The regulatory requirements for
biosimilars differ between
countries and regions around the
world.

147. • Not simply generics, but complex molecules requiring rigorous
development and approval processes.
•

149. Biosimilars

150. Benefits of
Biosimilars in
Rheumatology
• Can lead to significant cost
savings, improving access to
treatment for more patients.
Increased
affordability
• Drives down prices of original
biologics, benefiting healthcare
systems.
Enhanced
competition
• Enables treatment continuation
& better disease management.
Improved
long-term
sustainability
• Makes advanced therapies
more accessible to underserved
populations.
Broader
access to
innovation

151. A 40-year-old female
with psoriatic arthritis
& anterior uveitis
which failed topical
treatment, MTX &
cyclosporine. What is
the best option for
her?
Etanercept
Adalimumab
Tocilizumab
Rituximab
Secukinumab

152. The 2021 GRAPPA
Treatment
Recommendations

153. So, you started
adalimumab.
• Don’t forget that some
indications require loading.
• IBD
• Psoriasis
• Uveitis
• Hydradenitis suppurativa

154. Adalimumab 40 mg • 2 syringes once then 1 syringe after 1 week then 1 syringe/2
weeks

155. After 3 months, uveitis improved but
she complained of the affordability.
Can you switch to biosimilar?

159. So, she was switched
to Hyrimoz 40
syringe.
Her disease control
persisted.

160. • A biosimilar, unlike a "biomimic" or
"biocopy," which are medications
marketed in some countries, has
the same primary amino acid
sequence as the reference product
and has undergone rigorous
analytic & clinical testing in
comparison with its reference
product

161. ‫خيرا‬ ‫هللا‬ ‫جزاكم‬