Table 2.
Combination therapy of rituximab with intravenous immunoglobulins (IVIg) or immunoadsorption (IA).
| Study | Study design | Synopsis | Adverse events |
|---|---|---|---|
| RTX PLUS IVIg | |||
| Ahmed et al. (174) | Prospective, including 11 refractory PV patients, treated with 2 cycles of RTX 375 mg/Kg/m2 once a week for 3 weeks followed by a cycle of IVIg 2 g/Kg in the fourth week. Maintenance with RTX and IVIg infusions once a month for 4 months | 9 out of 11 patients achieved a complete remission in parallel with a rapid decreasing of the serum concentrations of anti-Dsg autoantibodies, which allowed successful discontinuation of steroids and adjuvant immunosuppressants. Clinical responses lasted 22–37 months (follow-up after discontinuation of RTX: 15–37 months). In 2 patients experiencing a relapse, retreatment with RTX was effective | No relevant side effects reported, including infections or infusion-related reactions |
| Ahmed et al. (175) | 10-year follow-up study of Ahmed et al. (174) | All the 10 patients previously treated with RTX and IVIg retained clinical remission after 10 years from the last RTX infusion | Not observed |
| Feldman et al. (205) | Retrospective, including 19 patients with refractory pemphigus. RTX was given at week 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, 24. IVIg were given at week 0, 4, 8, 12, 16, 20, 24 | 11 patients achieved long-term remission, allowing discontinuation of corticosteroids and other immunosuppressants. 8 suffered at total of 15 relapses. Re-treatment with RTX and IVIg was effective in achieving a long-term remission. Relapse was associated with incomplete B-cell depletion, B-cell repopulation and raise of serum anti-Dsg autoantibodies | Not reported |
| RTX PLUS IA | |||
| Behzad et al. (208) | Retrospective, including 10 patients with refractory PV. IA was administered at 4-week intervals, followed by RTX according to either the lymphoma protocol or the RA protocol | 8 out of 10 patients obtained a complete remission on therapy at 6 months following the first IA treatment. In 6 of them complete remission on therapy persisted at 12 months. Treatment with IA and RTX leads to a successful tapering of oral prednisone | No serious adverse events reported |
| Kasperkiewicz et al. (214) | Clinical series including 23 consecutive patients. IA was given on 3 consecutive days and repeated at initially 3 and then 4 weeks until lesions clearance of 90%. RTX 1,000 mg was infused at weeks 1 and 3. Patients also received intravenous dexamethasone pulses and oral azathioprine or mycophenolic acid | 19 patients achieved long-term complete remission. Over a period of a mean of 29-month follow-up, 6 patients suffered a relapse | A Staphylococcus aureus sepsis associated with an infected central intravenous line and an episode of extensive herpes simplex infection |
| Kolesnik et al. (215) | Retrospective, including 4 patients with PV and 2 with PF. The treatment protocol included a combination of protein A IA and RTX (375 mg/m2 once a week the day after each IA session) (Magdeburg treatment protocol). Patients with sub-epidermal blistering dermatoses were also included | Complete or partial remission was observed in 88 and 12% of patients, respectively, within an average follow-up of 22 months. Relapse occurred in one patient with PF. Treatment was associated with a substantial decrease of serum autoantibody concentrations | Erysipelas at the lower leg of one patient due to trauma |
| RTX PLUS IVIg PLUS IA | |||
| Shimanovich et al. (216) | Clinical series, including 5 patients with PV and 2 with PF. Treatment included a combination of protein A IA and RTX (375 mg/m2 once a week per 4 consecutive weeks). All patients received adjuvant immunosuppressive therapies. IVIg were given in non-responder patients | Long-term remission was achieved by 3 patients. Partial remission was induced in 1. Three refractory patients achieved long-term disease control following IVIg therapy | Staphylococcus aureus bacteremia, deep venous thrombosis and P. carinii pneumonia |
RTX, rituximab; IA, immunoadsorption; IVIG, intravenous immunoglobulins; PV, pemphigus vulgaris; PF, pemphigus foliaceus; RA, rheumatoid arthritis.