Table 1 Rituximab use in refractory non-infectious uveitis and scleritis - summary of comprehensive literature review

Number of Studies

31

36

Total Patients

108

121

Age

(years)

Mean 39.8±19.4

Median 40.0

Range 8.0-86.0

Mean 48.5±16.6

Median 52.0

Range 16.0-81.0

Gender

0.26:1 (M:F)

0.56:1 (M:F)

Ocular Condition

Treated with Rituximab

(Ratio, %)

Posterior uveitis (57/108, 52.8%);

Anterior uveitis (30/108, 27.8%);

Panuveitis (13/108, 12.0%);

Unspecified uveitis (4/108, 3.7%);

Anterior and intermediate uveitis (2/108, 1.9%);

Intermediate uveitis (1/108, 0.9%);

Anterior and posterior uveitis (1/108, 0.9%);

Anterior scleritis (71/121, 58.7%);

Episcleritis (7/121, 5.7%);

Posterior scleritis (7/121, 5.7%);

Anterior and posterior scleritis (3/121, 2.5%);

Location unspecified (33/121, 27.3%)

Underlying Systemic

Condition

(Ratio, %)

npAIR (30/107, 28.0%) [14,15,16,17,18,19,20,21,22];

Juvenile idiopathic arthritis (21/107, 19.6%) [23,24,25,26];

Vogt-Koyanagi-Harada disease (12/107, 11.2%) [27,28,29,30];

Behçet disease (11/107, 10.3%) [31, 32];

Cancer-associated retinopathy (10/107, 9.3%) [14, 33,34,35,36];

Sarcoidosis (4/107, 3.7%) [37];

Granulomatosis with polyangiitis (3/107, 2.8%) [38,39,40];

Systemic lupus erythematosus (2/107, 1.9%) [40];

Birdshot chorioretinopathy (1/107, 0.9%) [41];

HLA-B27 (1/107, 0.9%) [40];

Multiple sclerosis (1/107, 0.9%) [42];

Melanoma-associated retinopathy (1/107, 0.9%) [14];

Type 2 essential cryoglobulinemia (1/107, 0.9%) [43];

Indeterminate (9/107, 8.4%) [24, 40, 44, 45]

GPA (75/121, 62.0%) [11, 24, 38, 39, 46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66];

Rheumatoid arthritis (15/121, 12.4%) [48, 55, 60, 67,68,69,70];

ANCA-associated vasculitis, NOS (5/121, 4.1%) [37];

GPA and Rheumatoid arthritis (3/121, 2.5%) [56];

GPA and IgG4-related disease (1/121, 0.8%) [71];

Microscopic polyangiitis (1/121, 0.8%) [60];

Sjogren's syndrome (1/121, 0.8%) [12];

HLA-B27 (1/121, 0.8%) [40];

Behcet's disease (1/121, 0.8%) [24];

Mixed connective tissue disease

and Scleroderma (1/121, 0.8%) [55];

IgG4-related disease (1/121, 0.8%) [72];

Cogan syndrome (1/121, 0.8%) [48];

Indeterminate (15/121, 12.4%) [48, 55, 60, 70, 73, 74]

Treatment Prior to Rituximab

(Ratio, %)

Corticosteroid only (18/90, 20.0%)

1 Steroid sparing agent (19/90, 21.1%);

2 Steroid sparing agents (11/90, 12.2%);

≥3 Steroid sparing agents (37/90, 41.1%);

None (5/90, 5.6%)

Corticosteroid only (4/94, 4.3%)

1 Steroid sparing agent (30/94, 31.9%)

2 Steroid sparing agents (27/94, 28.7%)

≥3 Steroid sparing agents (31/94, 33.0%);

None: (2/94, 2.1%)

Previously Utilized Immunosuppressants

(Ratio, %)

Corticosteroids (69/85, 81.2%);

methotrexate (39/85, 45.9%);

cyclosporine (30/85, 35.3%);

adalimumab (24/85, 28.2%);

infliximab (24/85, 28.2%);

mycophenolate mofetil (24/85, 28.2%);

etanercept (15/85, 17.6%);

azathioprine (11/85, 12.9%);

IVIG (8/85, 9.4%);

chlorambucil (4/85, 4.7%);

leflunomide (4/85, 4.7%);

cyclophosphamide (3/85, 3.5%);

hydroxychloroquine (3/85, 3.5%)

tacrolimus (2/85, 2.4%);

abatacept (2/85, 2.4%)

anakinra (1/85, 1.2%)

sulfasalazine (1/85, 1.2%);

interferon-alpha (1/85, 1.2%);

bortezomib (1/85, 1.2%)

Corticosteroids (62/90, 68.9%);

cyclophosphamide (55/90, 61.1%);

methotrexate (42/90, 46.7%);

mycophenolate mofetil (24/90, 26.7%);

azathioprine (24/90, 26.7%);

infliximab (12/90, 13.3%);

NSAID (11/90, 12.2%);

etanercept (10/90, 11.1%);

adalimumab (9/90, 10.0%);

cyclosporine (8/90, 8.9%);

leflunomide (6/90, 6.7%);

hydroxychloroquine (3/90, 3.3%);

IVIG (2/90, 2.2%);

sulfasalazine (2/90, 2.2%);

doxycycline (2/90, 2.2%);

Unspecified anti-TNF agent (2/90, 2.2%);

anakinra (1/90, 1.1%);

minocycline (1/90, 1.1%);

interferon alpha (1/90, 1.1%);

golimumab (1/90, 1.1%);

Abatacept (1/90, 1.1%);

Chlorambucil (1/90, 1.1%);

Tocilizumab (1/90, 1.1%);

Cytarabine (1/90, 1.1%)

Line of Therapy

(Ratio, %)

First line (5/90, 5.6%);

Second line (18/90, 20.0%);

Third or greater (67/90, 74.4%)

First line: (2/96, 2.1%);

Second line: (4/96, 4.2%);

Third line: (90/96, 93.8%)

Treatment Regimen and Number of Cycles

(Ratio, %)

Rheumatologic protocol (45/87, 51.7%);

Other (19/87, 21.8%);

Foster protocol (18/87, 20.7%);

Oncologic protocol (5/87, 5.7%).

1 treatment cycle: (27/88, 30.7%);

2 treatment cycles: (26/88, 29.5%)

>2 treatment cycles: (35/88, 39.8%)

Rheumatologic protocol (87/114, 76.3%);

Other (11/114, 9.6%);

Foster protocol (10/114, 8.8%);

Oncologic protocol (6/114, 5.3%)

1 treatment cycle: (34/95, 35.8%);

2 treatment cycles: (18/95, 18.9%);

>2 treatment cycles: (43/95, 45.3%)

Types of Responses

(Ratio, %)

Responsive (81/97, 83.5%)

- Disease Remission (51/81, 63.0%)

- Author report: (30/81, 37.0%)

Nonresponsive (16/97, 16.5%)

Responsive (112/120, 93.3%)

- Disease Remission: (99/112, 88.4%)

- Author report: (13/112, 11.6%)

Non-responsive (8/120, 6.7%)

Incidence of Recurrence

(Ratio, %)

24/81, 29.6%

33/107, 30.8%

Adverse Events

(Ratio, %)

None (74/97, 76.3%);

Unspecified Infusion reaction (6/97, 6.2%);

neutropenia (2/97, 2.1%);

conjunctivitis (2/97, 2.1%);

GI discomfort (1/97, 2.1%);

herpes zoster (1/97, 2.1%);

leukopenia (1/97, 1.0%);

pneumonia (1/97, 1.0%);

flushing (1/97, 1.0%);

ventricular tachycardia (1/97, 1.0%);

Staphylococcus aureus skin infection (1/97, 1.0%);

fungal skin infection (1/97, 1.0%);

unspecified dermatitis (1/97, 1.0%);

UTI (1/97, 1.0%);

Sinusitis (1/97, 1.0%);

Abdominal pain, dryness, eyelid swelling (1/97, 1.0%);

Sinusitis, herpes zoster, nodular scleritis (1/97, 1.0%)

None (71/83, 85.5%);

Itching (infusion reaction) (2/83, 2.4%);

Disease exacerbation (2/83, 2.4%);

Pneumonia and septic shock (1/83, 1.2%);

Herpetic mouth ulcers (1/83, 1.2%);

Acute retinal necrosis (1/83, 1.2%);

Herpes zoster (1/83, 1.2%);

Hypotension (Infusion reaction) (1/83, 1.2%);

Ocular hypertension (1/83, 1.2%);

Dry eyes, weight loss, fatigue, and joint pain (1/83, 1.2%);

Bronchitis, bacterial pneumonia,

leukopenia, and anemia (1/83, 1.2%)