Table 1 Studies on rituximab associated with intravenous Immunoglobulin in pemphigus

Ahmed et al., 2006 [12].

Open prospective uncontrolled

USA

11

Mean = 38 yo

55% females

PV

30 to > 96 mo

Months 1 and 2- RTX (375 mg/m² once a week for 3 weeks) + IVIg (2 g/kg in the fourth week).

Months 3, 4, 5, and 6 – a single infusion of RTX + 2 g of IVG / month.

If the patient was disease-free: − 7 additional IVIg infusions.

37 mo.

All patients had improvement between 3rd and 6th infusions of RTX;

Complete clearance between 7th and 9th infusions;

9/11 (82%) had sustained remission (mean of 31.1 mo).

All immunosuppressive drugs were discontinued.

None

Mühlhoff and Megahed, 2007 [13].

Case report

Germany

1

44

PV

4 years

RTX- 375 mg/m² once a week for 3 weeks.

In the fourth week, IVIg 500 mg/kg/day for 3 days and then RTX plus IVIg per month for 9 months

ND

Clinical improvement and reduction in prednisolone to 5 mg/day.

Significant decrease in anti-desmoglein 1 and 3 titers.

None

Foster et al., 2010 [11].

Retrospective,

Comparative

Interventional case series

USA

12 - divided into 2 groups

Group 1- mean age = 57 yo;

Group 2- mean age = 63 yo

50% females

Ocular cicatricial pemphigoid

Group 1→ 21 mo;

Group 2→18.5 mo.

Group1→6 patients received RTX (375 mg/m²/week for 8 weeks followed by once monthly for 4 mo) and IVIg (2 g/kg per cycle →1 cycle/month until B cell level returned to normal and after that at intervals of 6,8,10,12,14 and 16 weeks)

Group 2 →6 patients received aggressive immunosuppression.

Group 1→ median 55.5 mo

Group 2→ median 27.5 mo.

Group 1- no further deterioration of visual acuity;

Group 2- decrease in visual acuity; all patients were blind at the end of the study

None

Feldman et al., 2011 [14].

Retrospective

USA

19

Mean = 51 ± 9 yo

97% females

PV

ND

RTX- 375 mg/m² once a week for 8 weeks and then every 4 weeks until week 24 weeks; IVIg 2 g/kg once a month.

29.6 mo in the LTR group;

40 mo in the relapse group.

11/19 (58%) achieved long-term clinical remission;

8/19 had 15 relapses.

ND

Ahmed et al., 2015 [17].

Retrospective

USA

12

Mean age – 68.2 yo;

58.3% females.

Bullous pemphigoid

36.5 mo

Phase 1- IVIg 2 g/kg/cycle - at monthly intervals + 8 infusions of RTX (375mg/m²) weekly;

Phase 2- IVIG multiple cycles at monthly intervals depending on CD19 + B cell count;

Phase 3–6 cycles of IVIg given at 6-, 8-, 10-, 12-, and 14-week intervals

Mean = 73.8 mo

Control of disease activity was observed in a mean of 4.15 (range 2.3–6.8) weeks;

Two patients relapsed (one after 22 mo and the other after 18 mo) but refused additional infusion of RTX.

None

Namba et al., 2016 [15].

Case report

Japan

1

59

Female

Paraneoplastic pemphigus + bronchiolitis obliterans +

B cell lymphoma

1 mo

375 mg/m² weekly for 3 weeks for 5 cycles; IVIg 400 mg/kg over 5 days once a month for 3 cycles, associated with steroid (pulse) and cyclosporin

+ R-CHOP for lymphoma

6 mo

No clinical response (skin but not mucosal improvement);

Patient died after six months from bronchiolitis obliterans

Infections (bacterial, fungal, and cytomegalovirus).

Steger et al., 2016 [18].

Case series

UK

4

Pat1: 54 yo; male;

Pat 2: 83 yo; male;

Pat 3: 63 yo, female;

Pat 4: 21 yo, male

Autoimmune cicatricial conjunctivitis

(3 with mucous membrane pemphigoid and 1 with linear IgA disease)

Pat 1: 17 mo;

Pat 2: 3 mo;

Pat 3: 0;

Pat 4: 2 mo

RTX: 1.000 mg- twice with 2 weeks interval;

IVIg: 2 g/kg divided into 3 daily doses.

Pat1: 2 courses of RTX + 3 courses of IVIg with 1 st infusion of RTX and 6 courses parallel to 2nd infusion of RTX.

Pat 2 and 4: 1 course of RTX + 2 courses of IVIg.

36, 32, 65, and 42 mo, respectively.

Conjunctival inflammation settled in all cases; fornical shortening continued throughout 8–12 mo without the active conjunctival disease.

Reasonable visual acuities were maintained in all but 1 patient.

Pat 2- developed pneumonia + life-threatening septicemia. Same patient- corneal infection with corneal melting.

Hamadah et al., 2018 [16].

Retrospective

Saudi Arabia

23 (*)

Mean = 45 yo;

48% females

15 PV,

5 PF,

1 each with:

-P. erythematosus,

-P. vegetans,

-P. herpetiformis.

31 mo

RTX- 375 mg/m² once a week for 3 weeks.

In the fourth week, IVIg 2 g/kg over 3 days

69 (8-126) months

90.5% achieved complete remission

17%- infusion reactions.

8% -cellulitis,

8%-cytopenias,

4% - molluscum contagiosum;

1 patient died from MI (not related to therapy).

Narayanan et al., 2021 [20].

Case report

India

1

32 yo

Female

Pemphigoid gestationis

From 2 mo before delivery to 6 mo post-partum

IVIg- 30 g/day for 5 days (3 courses 2 weeks apart);

RTX – 1 g, 2 doses, 2 weeks apart)

Azathioprine after second course of IVIg

6 mo

All the lesions had resolved one month after the 3rd course of IVIg.

ND

Foschi et al., 2022 [19].

Case report

USA

1

73 yo

Male

PV

10 years

375 mg/m² RTX/week for 3 weeks.

After the 4th week, IVIG (2 g/kg/month)

+

methylprednisolone (96 mg)

ND

PV improved, and glucocorticoid was tapered.

Deep vein thrombosis;

Pneumonia by P. carinii