This document discusses various biological agents used to treat uveitis, including tumor necrosis factor inhibitors like infliximab, adalimumab, etanercept, golimumab, and certolizumab. It provides dosing information and potential adverse effects for each drug. Anti-interleukin therapies like daclizumab, anakinra, tocilizumab, rituximab, gevokizumab, and secukinumab are also summarized. Key points are provided on initiating and monitoring patients on biological therapies to help maximize efficacy and safety. Biologics are described as potent treatments for uveitis when conventional therapies have failed or been poorly tolerated.

1. Biologicals in uveitis

2. Tumor necrosis factor inhibitors
Infliximab
Adalimumab
Etanercept (both TNF α , β)
Golimumab
Certolizumab

3. Infliximab (Remicade)(Infmab)
IV
loading dose at weeks 3-5 mg/kg 0, 2, and6, wk maintenance
3-10 mg/kg every 4-8 weeks
(20 mg/kg maximum in children)
AE: Susceptibility to infections,
reactivation of TB, histoplasmosis, hepatitisB,
fungal infection
autoantibody production

4. Most commonly used biologic agent in the treatment of
uveitis
its efficacy has been particularly promising, especially
in sight-threatening Behcet’s uveitis
Successful treatment has also been reported for
sarcoidosis,
birdshot chorioretinopathy, and
multifocal choroiditis.

5. Adalimumab (Humira)(Exemptia) (Adfrar)
SC
40 mg every 1-2 weeks
loading doses of 80-160 mg
AE: Hypersensitivity reactions;
demyelinating disease;
lupus-like syndrome;
malignancy;
thromboembolic events;
congestive heart failure

6. to conclude,
 ADA is a well-tolerated drug helpful
in decreasing inflammatory activity in refractory uveitis
to reduce steroid requirement
proven to be a more effective alternative in patients
not responsive or
allergic to IFX.

7. Etanercept (Enbrel)
 SC
 Adults 50 mg weekly (may be given
50 mg twice weekly for frst 3 months
for PSA); children 0.8 mg/kg/week
(max 50 mg/week)
The final conclusion
ocular inflammation is paradoxically a potential adverse effect
of etanercept, even in previously uninvolved eyes, although
minority of the patients treated

8. Golimumab (Simponi)
SC
50 mg SC monthly; except for UC
200 mg at week 0, 100 mg at week 2,
then 100 mg every 4 weeks
There are a few case reports on successful use of golimumab
in JIA-associated uveitis and Behcet’s uveitis

9. Certolizumab (Cimzia)
SC
400 mg SC at weeks 0, 2, and 4, then
200 mg every 2 weeks or 400 mg every 4 weeks

10. Anti-interleukin therapies
Daclizumab
Anakinra
Tocilizumab
Rituximab
Anakinra
Gevokizumab (XOMA 052)
Secukinumab (anti-interleukin-17A antibody

11. Daclizumab (Zenapax)
 T cells (IL-2)
 IV, SC
1-2 mg/kg every 2 or 4 weeks
AE :Hypersensitivity reactions; headache;
gastrointestinal upset
Daclizumab has been demonstrated
effective for refractory birdshot retinochoroidopathy in one
study

12. Anakinra (Kineret)
 IL-1 receptor
SC
100 mg daily Injection-
AE: site reaction infections,
neutropenia especially if concurrently used
withTNF-inhibitors
more effective in the treatment of CINCA syndrome than
corticosteroids (chronic infantile
neurological cutaneous articular (CINCA) syndrome)

13. Tocilizumab (Actemra)
IL-6 receptor
IV
4 mg/kg infusion over 1 hour every
4 weeks, can increase to 8 mg/kg
based on response
AE : Infections; neutropenia; thrombocytopenia; transaminitis
Tocilizumab may represent
a treatment option for otherwise refractory JIA-associated
uveitis

14. Anakinra
competitively inhibits binding of IL-1
more effective in the treatment of CINCA syndrome than
corticosteroids.
Subcutaneous
dose1 mg/kg/day until remission
was acheived Inflammatory remission was achieved within
the 1st year of treatment,
No adverse side effects were reported.

15. Gevokizumab (XOMA 052)
granted orphan drug status in the
European Union for non infectious uveitis.
single infusion of XOMA 052 (0.3 mg/kg)
resulted in a rapid onset and
sustained reduction in intraocular inflammation in patients
with resistant uveitis and retinal vasculitis.

16. Secukinumab (anti-interleukin-17A antibody)
Secukinumab is a fully humanized IgG1k monoclonal antibody
neutralizing IL-17A.
It has proved to be quite effective in the
treatment of patients with anterior and posterior uveitis with
no serious adverse effects

17. Rituximab (Rituxan (Reditux) (Ristova)
B-cells (CD20)
IV
500 or 1000 mg at week 0 and 2
AE: Infusion reactions; severe mucocutaneous reactions;
hypertension; bronchospasm; progressive multifocal
leukoencephalopathy

18. Rituximab
a promising effective treatment option for refractory uveitis
associated with JIA leading to long-term quiescence of uveitis,
particularly for patients who have not previously responded
to other biologic therapies
It has been effective for treatment
of various systemic vasculitis associated uveitis, retinal
vasculitis, and scleritis.

19. Interferons
Interferon α-2a (Roferon)
SC
3-6 million IU/day tapering over 6 months
AE: Injection site reaction, flu-like reaction, bone marrow
suppression
Few case reports on successful use of abatacept
in refractory uveitis

20. Fusion protein of CTLA-4(CTLA: Cytotoxic T-lymphocyte antigen)
Abatacept (Orencia)
T-cells (CTLA-4)
IV
500 or 1000 mg at week 0, 2, 4 then
every 4 weeks (children: 10 mg/kg,
maximum 1000 mg)
AE: Serious infections; allergic reactions; malignancy; respiratory
problems in patients with chronic obstructive pulmonary
disease

21. Things to Remember for Patients on
Biologics
1. It is contraindicated in patients with tuberculosis (TB),
chronic hepatitis B or C, or any active infection
2. IFX, etanercept, and ADA, all have been categorized as the
United States Food and Drug Administration category B
for use in pregnancy
Avoid pregnancy till 5 months after stopping the last dose
of biologics
3. Rule out malignant conditions before starting biologics

22. 4. Patient to be advised to see a doctor if he develops fever,
sore throat, bleeding
5. As TNF-α agents can aggravate multiple sclerosis, rule out
demyelinating disease before starting these agents in those
set of patients
6. Common side effects:
• Reduced immunity leading to increased risk of infection
including flare-up of latent TB
• Worsening of heart failure if already present, so
contraindicated in the New York Heart Association
Class III/IV heart failure.

23. Key Points for Initiating and Monitoring
Patients on Biological Therapies
1. Before starting biologics, a careful clinical examination is
important to rule out previous cardiac diseases, malignancy,
neurological disorders, or infections
2. The patient who will be treated with biologics should know
the main signs and symptoms (“red flags”) of the adverse
effects associated with their use
3. Laboratory tests
• Annual TB skin test; alternatives include the
QuantiFERON®-TB gold blood test and chest X-ray if
indicated
• Complete metabolic panel with liver function tests for
each IFX infusion and with any sign of hepatic injury

24. • Complete metabolic panel (renal function test, electrolyte,
liver function test, and glucose) every 3–6 months on all
biological therapies
• Complete blood counts every 3–6 months on all biological
therapies
• Hepatitis screen and human immunodefciency virus
testing when risk factors present on all biological
therapies.
4. Patients initiating anti-TNF therapy should be up-to-date
for pneumococcal, influenza (nonlive virus), and hepatitis
B vaccines. Patients receiving anti-TNF therapy should not
have live virus vaccine, including varicella zoster, oral polio,
or rabies vaccination

25. Conclusion
Biologics are potent medications and very useful when
conventional immunosuppressive therapy
has failed or
hasbeen poorly tolerated, or
to treat concomitant ophthalmic
and systemic inflammation that might benefit from these
medications, such as those with RA, JIA, AS, BD, and
inflammatory bowel disease.

26. IFX and ADA can be considered as the first-line
immunomodulator for the treatment of ocular manifestations
of Behcet’s disease and
 as the second-line immunomodulatory
agent for the uveitis associated with juvenile arthritis and
seronegative spondyloarthropathy with good quality
evidence.
The literature for ADA is less developed than
for IFX, but these agents seem to show similar efficacy in
most studies. Until more comparative data are available, no
recommendation can be made as to preferred agent although
numerous studies have suggested that ADA may be effective
in patients who have become intolerant to or have developed
reduced clinical responsiveness to IFX.

27. Evidence suggests that etanercept may not be as effective for
uveitis as IFX and ADA and it has been associated with
development of uveitis in JIA patients and development of
sarcoid-like disease in others.
Other agents, such as golimumab, abatacept, gevokizumab,
and tocilizumab, may have great future promise for the
treatment of noninfectious uveitis.
 An ophthalmologist
should seek to treat the patient, rather than simply suppress
the uveitis. As such, it is important to take a holistic approach
to treatment.

28. Due to limited data from randomized clinical trials on
biologic agents for uveitis, many studies are currently
underway. Because the pool of patients with uveitis is not that
large, it is not easy to do clinical trials.
 A major unanswered question is whether biologic therapies will
be effective if delivered locally to the eye. New drugs and
innovative drug delivery systems
will pave the way for future treatments in uveitis.
It is crucial that we continue to develop new therapies for
use in uveitis that aims to suppress disease activity, prevent
accumulation of damage, and preserve visual function for
patients with the minimum possible side effects.

29. Thank you