Our systematic literature search revealed one prospective case series using OBI in three patients with phospholipase A₂ receptor (PLA₂R)-mediated membranous nephropathy who had previously been refractory to treatment with RTX (26). The duration of the study was 27 months for the first two cases and 30 months for the third case. The article does not mention the source of funding of the study.

The first patient (case 1, 54-year old white woman) presented with nephrotic syndrome, diagnosed as PLA₂R-associated membranous nephropathy based on a kidney biopsy. She showed persistently elevated anti-PLA₂R antibody titers and severe proteinuria despite a treatment with two courses (six months apart) of twice 1 g RTX. Thus, the patient was premedicated with 40 mg intravenous (IV) methylprednisone plus 25 mg oral diphenhydramine and 650 mg oral acetaminophen, followed by treatment with 1 g OBI, given 100 mg IV the first day and 900 mg IV the second day, to reduce possible infusion reactions. 12 and 18 months after treatment with OBI, the patient’s anti-PLA₂R antibody titers and proteinuria became low and kept on decreasing, respectively, along with an improvement of serum albumin and serum creatinine concentrations.

The second patient (case 2, 61-year old white man) had also nephrotic syndrome, diagnosed as PLA₂R-associated membranous nephropathy based on a kidney biopsy. He was treated with cyclosporine and prednisone, which resulted in a transient improvement of anti-PLA₂R antibody titers and proteinuria. Because proteinuria continued to be severe, he was given prednisone and cyclophosphamide, which did not improve the patient’s situation, followed by discontinuation of cyclophosphamide after nine months of treatment and administration of RTX. Despite these treatments, the patient showed an increase in anti-PLA₂R antibody titers and very severe proteinuria, which motivated a treatment with OBI, given 100 mg IV on day 1, 900 mg IV on day 2, and 1 g IV on day 8, along with a premedication similar to case 1. Seven and nine months after treatment with OBI, the patient’s anti-PLA₂R antibody titers and proteinuria became low and kept on decreasing, respectively, along with an improvement of serum albumin and serum creatinine concentrations.

The third patient (case 3, 54-year old white man) also presented with nephrotic syndrome, diagnosed as PLA₂R-associated membranous nephropathy based on a kidney biopsy. He received a treatment with two courses (three months apart) of twice 1 g RTX, following which his anti-PLA₂R antibody titers decreased, however, his severe proteinuria remained unchanged. Thus, a treatment with OBI was initiated, given 100 mg IV on day 1, 900 mg IV on day 2, and 1 g IV on day 15. Six, 18 and 24 months after receiving OBI, the patient’s anti-PLA₂R antibody titers remained undetectable and his proteinuria decreased and kept on decreasing, along with an improvement of serum albumin concentrations.

Only one adverse event was noted during treatment with OBI. Patient 3 experienced localized herpes zoster reactivation, which was managed conservatively. There were no other adverse events (AEs) or serious adverse event (SAEs).

The health-related QoL was not assessed.

Synopsis: Based on a case series of three patients with PLA₂R-associated membranous nephropathy whose disease was refractory to treatment with RTX, OBI was more efficacious than RTX in reducing proteinuria and improving serum albumine concentrations. RCTs are needed to confirm these promising results.

We found one multicenter double-blind RCT comparing OBI to placebo treatment in 125 patients with SLE and proliferative lupus nephritis (27). All patients received maintenance treatment with MMF and corticosteroids. Furthermore, concomitant treatment with an antimalarial drug, angiotension-converting enzyme inhibitor, angiotensin II receptor blocker, calcium and vitamin D was allowed.

62 patients received placebo and 63 patients OBI. OBI was administered at a dose of 1000 mg on day 1, week 2, week 24, and week 26. The primary endpoint, proportion of patients with complete renal response – measured by urine protein-to-creatinine ratio of less than 0.5, normal serum creatinine and inactive urinary sediment – at 52 weeks was met more often in patients treated with OBI, but the difference was not statistically significant between OBI and placebo (p = 0.115). However, significantly more patients in the OBI group reached an overall renal response (p = 0.025). Although clinical endpoints did not differ markedly between OBI and placebo, patients receiving OBI significantly increased complement factors C3 and C4 and significantly decreased titers of anti-double stranded DNA antibodies.

91% of patients receiving OBI experienced at least one AE and 25% had a SAE. There was one death in the OBI group caused by a gastrointestinal perforation. Urinary tract infection and bronchitis were the most common AEs.

Synopsis : This RCT in SLE with active lupus nephritis showed little efficacy of OBI on disease progression when compared to placebo. Further studies with different dosing regimens of OBI are needed to draw a conclusion.

We identified four double-blind placebo-controlled RCTs, one open-label extension study, and one substudy with predefined endpoints using OCR in patients suffering from MS (28–32). Study duration varied from 24 to 192 weeks. All studies were funded by the industry.

In total 2621 patients with relapsing-remitting multiple sclerosis (RRMS) (28, 29) and 732 patients with primary progressive multiple sclerosis (PPMS) (29) were treated with either OCR or a control medication. In three of the studies diagnosis was made based on the McDonald criteria (29–31). Predefined expanded disability status scale (EDSS) had to be between 0 and 6.5 and all patients had to be at least 18 years of age.

In the first study, published in 2011, patients in the active treatment arms received IV OCR (300 mg or 1000 mg) on days 1 and 15 and again on day 1 (600 mg or 1000 mg, respectively) of the second, third, and fourth cycle (weeks 24, 48 and 72) (28). The control group was treated with matching placebo. A fourth treatment arm received open-label interferon-β-1a weekly until week 24. The placebo and interferon-β-1a arms were both offered two doses of OCR (300 mg) on days 1 and 15 of the second, third, and fourth cycle. The OPERA I and II trials used a similar treatment regimen administering 600 mg of IV OCR every 24 weeks compared to interferon β-1a (29). The only study available in patients with PPMS used the same dosing regimen for OCR compared to placebo (29). 100 mg IV methylprednisolone was given as premedication in all four studies. The primary endpoint was either the total number of gadolinium-enhancing (GdE) T1 lesions at weeks 12, 16, 20, and 24, the annualized relapse rate at week 96, the percentage of patients with a disability progression at week 12, or the proportion of infusion-related reactions (IRR). Secondary endpoints comprised the relapse rate, disability progression, proportion of relapse-free patients, safety, as well as various assessments concerning MRI lesions.

The mean number of GdE T1 lesions, the primary endpoint of the study by Kappos et al., decreased significantly as compared to placebo (28). There was an 89% reduction in the 300 mg group (p<0.0001) and a 96% reduction in the 1000 mg group (p<0.0001). Furthermore, the annualized relapse rate was significantly reduced and the total number of new and persisting GdE lesions was significantly lower in both OCR groups.

In the OPERA I and II trials, also conducted in patients with RRMS, there was also a significant reduction (46% and 47%, respectively) in the annualized relapse rate as compared to interferon-β-1a (29). Thus, the primary endpoint was achieved. Furthermore, OCR led to a significant decrease in GdE lesion on T1 MRI and a reduced number of new or newly enlarged T2 lesions. After completion of the double-blind phase, patients could enter an open-label extension trial, where OCR was administered at a dose of 600 mg every 24 weeks (32). The trial was planned for a duration of eight years, with results of the three-year follow-up available currently. Annualized relapse rates remained low in the group previously receiving OCR and continuing to receive OCR during the open-label extension phase. Moreover, there was a significant reduction in annualized relapse rates in the group receiving interferon-β-1a during the double-blind period, followed by OCR during the open-label extension phase. A significant difference between these two groups in terms of mean change in EDSS, brain atrophy, and clinical disease progression remained in the open-label extension phase. No significant differences were noted concerning the number of MRI lesions. Safety data during the extension phase were consistent with the double-blind phase.

Remarkably, results in patients with PPMS were similar to those seen in patients with RRMS. There was a significant reduction in disease progression as early as week 12 (29). The results remained significant until at least week 24. Furthermore, patients in the OCR group had a significantly smaller volume of hyperintense T2 lesions and a significantly smaller change in brain volume.

The ENSEMBLE PLUS substudy in patients with RRMS investigated the occurrence of IRRs in patients receiving OCR at a conventional infusion rate amounting to an infusion time of 3.5 hours versus a shorter infusion time of 2 hours (31). Primary endpoint was the proportion of patients with IRRs following the first dose of OCR. Although there was a slight increase in IRRs in patients receiving the shorter infusion rate, this difference was not significant and there were no serious IRRs in either group. Thus, a shorter infusion rate was considered safe.

AEs and SAEs occurred at a similar frequency in patients treated with OCR, interferon-β-1a, and placebo. Nine patients died during the studies, including two cases of suicide (29), one road-traffic accident (30), one mechanical ileus (29), one pulmonary embolism (30), one pancreatic carcinoma (30), one systemic inflammatory response syndrome of unknown cause (28), one case of pneumonia (30), and one case of aspiration (30). The number of deaths during the open-label extension study was unavailable.

The health-related QoL was assessed in neither of the studies.

Synopsis: Above-mentioned trials demonstrated a superiority of OCR above placebo and interferon-β-1a leading to the approval of the drug by the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) for the use in patients with RRMS and PPMS.

Five placebo-controlled, double-blind RCTs using OCR in patients with RA met our inclusion criteria (33–37). The study durations ranged from 48 to 104 weeks, including two trials, which were terminated early (34, 36).

2835 patients participated in either of the trials. Main inclusion criteria were diagnosis of RA according to the 1987 revised American College of Rheumatology (ACR) criteria and active disease. In most studies a minimum disease duration of three months was required for inclusion. Inflammatory joint disease other than RA and systemic involvement secondary to RA were the most common exclusion criteria (35–37).

OCR was usually given two weeks apart at doses ranging from 10 mg to 1000 mg with either concomitant methotrexate or leflunomide. In all but one trial (37), other disease-modifying antirheumatic drugs (DMARDs) had to be discontinued four weeks prior to enrollment (33–36). Premedication consisted of 100 mg IV methylprednisolone with the exception of the ACTION trial (33). All patients were allowed to use acetaminophen and an antihistamine as premedication (34–37).

Three studies assessed the ACR20 response rate as primary endpoint (34, 35, 37). In contrast, the FILM trial was planned to investigate the change in the van der Heijde-modified total Sharp score at week 104, but due to early termination this endpoint was analyzed earlier at week 52. The ACTION trial (33) analyzed safety events as primary outcome measure. Secondary endpoints comprised ACR50/70 response rates, change in the health assessment questionnaire–disability index, remission rate according to the 28-joint disease activity score (DAS28), and European League Against Rheumatism (EULAR) responses.

Rigby et al. (35), Stohl et al. (36), and Tak et al. (37), reported significant results concerning ACR20, ACR50, and ACR70 response rates as well as DAS28-erythrocyte sedimentation rate (ESR) remission rates. One of the two remaining trials reported significant ACR20 response rates in all OCR-treated patients while ACR50 response rates were only significant in two OCR arms (50 mg and 200 mg) (34). The last trial did not report any p-values concerning those endpoints (33).

There was no statistically significant difference in the occurrence of AEs between patients treated with OCR and patients receiving placebo. Although the STAGE and the SCRIPT studies reported comparable frequencies of SAEs and infections, the number of serious infections was elevated in patients receiving OCR leading to the early termination of two other trials (34, 36). In total 8/1951 patients receiving OCR and 5/1007 placebo-treated patients died.

Three studies assessed change in health assessment questionnaire–disability index as a marker for QoL (35–37). All three studies showed a significant improvement.

Synopsis: Although OCR led to significantly better results when assessing the ACR response rates as well as the DAS28-ESR remission rates, two studies reported increased rates in serious infections.

Only one double-blind, placebo-controlled RCT assessed the efficacy of OCR in patients with SLE (38). The study lasted 96 weeks. Patients with an adequate response at week 48 continued blinded treatment, whereas patients with an inadequate response had the option of open-label treatment.

378 patients were initially enrolled. Diagnosis of SLE according to the ACR criteria with active lupus nephritis class III/IV were the main inclusion criteria. Patients with an eGFR <25ml/min were excluded. Minimum age for inclusion was 16 years.

OCR (400 mg or 1000 mg) was given on days 1 and 15 followed by a single infusion at week 16 and every 16 weeks thereafter. The control group received matching placebo. A premedication consisting of methylprednisolone, acetaminophen, and an antihistamine was given. Furthermore, all patients received concomitant treatment with MMF (3 mg/d) or cyclophosphamide (500 mg IV every 2 weeks for 6 times) followed by a maintenance therapy with azathioprine.

The proportion of patients with a renal response at week 48 was the primary endpoint and was higher in patients receiving OCR. However, the difference was not statistically significant.

83.4% of the patients receiving OCR had at least one AE, which was comparable with the 88% in the placebo group. The percentage of patients with at least one SAE was also comparable, amounting to 28.85% vs 27.2% in the OCR and placebo group, respectively. Remarkably as in patients with RA, the rate of serious infections was increased at 18.2% in patients receiving OCR vs 14.4% in placebo-treated patients, leading to early termination of the study.

Influence on QoL was not assessed.

Synopsis: OCR improved the renal response rate, however, this change was not significant when compared to placebo. OCR led to an increased rate of serious infections.

There was only one case series eligible for our review. It tested the efficacy and safety of OFA in patients with ANCA-associated vasculitis (AAV) over a period of 2 years (39). Eight patients with a mean age of 52 years matched the only reported inclusion criteria being a diagnosis of AAV.

IV OFA was given at a dose of 700 mg on days 0 and 14. Concomitant treatment comprised 1 mg/kg oral prednisolone and 10 mg/kg cyclophosphamide, the latter given IV on days 0 and 14 and every 14 days thereafter. After three months, maintenance therapy with azathioprine or MMF was introduced. All patients received prophylactic co-trimoxazole for 3 months, a proton pump inhibitor, and calcium and vitamin D3 supplementation.

There were no predefined endpoints set. All patients achieved clinical remission by month 3. This was accompanied by the ability to taper corticosteroids and by a reduction in acute phase reactants. No relapse occurred during the first year of the study.

Five patients experienced an AE. None of them were considered severe AEs or SAEs.

QoL was not analyzed.

Synopsis: Currently available results seem promising, although OFA was only used in eight patients suffering from AAV. Further trials with a randomized-controlled design involving more patients are needed to confirm theses findings.

We found one prospective case series publication on treatment with OFA in three patients with PLA₂R-mediated membranous nephropathy (40).

Patient 1 was a 74-year-old man suffering from nephrotic syndrome positive for anti-PLA₂R antibodies. After ineffective treatment with RTX, he was assigned to receive three cycles of double-filtration plasmapheresis (DFPP) followed by OFA. Despite the depletion of B cells, anti-PLA₂R levels remained high and the nephrotic syndrome persisted leading to end-stage renal disease.

The second patient, a 69-year-old man, experienced an anaphylactic reaction after a single RTX infusion, which was associated with a transient reduction of anti-PLA₂R antibodies. Thus, he was offered a rescue therapy with OFA and DFPP. Six days after a 100 mg OFA infusion he received three cycles of DFPP. Anti-PLA₂R titers remained low for three months but increased again to pretreatment levels after six months. Accordingly, proteinuria persisted.

The third patient, a 80-year-old man, had very high anti-PLA₂R titers and was treated with 100 mg OFA followed by 4 cycles of DFPP. During follow-up, anti-PLA₂R antibody titers decreased and were undetectable at six months. Partial remission of nephrotic syndrome was observed.

The study did not report safety data or effects on QoL.

Synopsis : The available case series included only three patients with rather negative results. Only one of three treated patients achieved partial remission of kidney disease.

We identified four placebo-controlled RCTs using OFA in 1136 patients with RRMS (41–43) or secondary progressive MS (43) according to the McDonald criteria. The treatment period lasted 24, 48 weeks, and 30 months, respectively. Patients were aged between 18-55 years old and had an EDSS of 0 to 5 (41) or 5.5 (42, 43).

In the study of Sorensen et al. (41), patients received two doses OFA (100 mg, 300 mg, or 700 mg) or placebo IV two weeks apart. After 24 weeks, treatment was switched and another two infusions were administered in a blinded manner. The primary endpoint was safety. There were significant reductions noted in the number of new GdE T1 lesions, total number of GdE T1 lesions, and new and/or enlarging T2 lesions (41). However, there were no significant changes found in the EDSS score.

In the MIRROR study (42), patients received OFA 3 mg, 30 mg, or 60 mg every 12 weeks subcutaneously (SC). A fourth treatment arm received OFA 60 mg SC every four weeks. The cumulative number of new GdE lesions at week 12 was the primary endpoint and was found to be reduced by 65% in patients receiving OFA (p<0.001). However, there was no significant difference concerning EDSS and relapse rates (42).

The ASCLEPIOS I and II trials were multicenter RCTs conducted concurrently and following the same study design (43). 20 mg OFA were administered SC every four weeks with loading doses on days one, seven, and 14. After one month of treatment, patients were allowed to apply the medication at home. The control group received daily teriflunomide orally. Both groups received matching placebo in order to blind the study. The primary endpoint, reduction in annualized relapse rate, was achieved in both trials. For the secondary endpoints a pooled analysis of both trials was performed, which showed a significant reduction in disability worsening at three and six months, whereas there was no significant disability improvement noted. While there was a significant reduction in GdE T1 and T2 lesions in the OFA groups, the annually brain volume loss was comparable in the teriflunomide and OFA groups.

The frequency of AEs and SAEs was comparable between OFA and placebo in all studies. There was one death in the teriflunomide group of the ACLEPIOS II trial.

QoL was not analyzed.

Synopsis: Based on the available data, the FDA and EMA approved subcutaneous OFA for the treatment of patients with RRMS or secondary progressive MS.

Four placebo-controlled RCTs (44–47) including 852 patients investigating OFA in RA patients were included in our systematic review. The main inclusion criteria were diagnosis of RA according to the ACR criteria with a minimum disease duration of six months and a patient age of at least 18 years. In all but one trial (47), disease needed to be active. Concomitant treatment with DMARDs, another autoimmune disease, and significant comorbidity were the most important exclusion criteria.

Except in the trial by Kurrasch et al. (44) where patients received a single SC dose, IV OFA was given with a dosing interval of two weeks. IV doses ranged from 300 mg to 1000 mg. All patients were allowed to receive concomitant methotrexate and oral corticosteroids at stable dosages. In all, except the SC trial (44), non-steroidal anti-inflammatory drugs, analgesics and one inter-articular injection of corticosteroids were permitted. Premedication consisted of acetaminophen, an antihistamine, and corticosteroids. Only Kurrasch et al. did not administer corticosteroids as premedication (44).

Kurrasch et al. (44) and part A of Ostergaard et al. (45) investigated safety as primary endpoint. Part B of Ostergaard et al. (45) assessed the proportion of patients with an ACR20 improvement as primary endpoint, while the extension trial explored time to treatment withdrawal. The third RCT assessed the ACR20 response rate at week 24 (47). Secondary endpoints comprised pharmacokinetics, anti-drug antibodies, EULAR responses, DAS28 response, and B cell depletion.

Both studies with available results demonstrated significantly better outcomes for OFA-treated patients (p<0.001 for both studies) when ACR20 was assessed. Ostergaard et al. also proved superiority in ACR50 response rates and proportion of patients with EULAR good or moderate response (45). Similarly, Taylor et al. (47) reported significantly better results concerning ACR50/70 response rates, proportion of patients with good or moderate EULAR response, and change in DAS28-ESR or DAS28–C-reactive protein. The open-label study of Quattrocchi et al. was terminated early due to the study sponsor’s refocus on the investigation of SC administration and no efficacy results were available at study termination (46). Kurrasch et al. did not report markers of disease activity (44).

All four studies determined the occurrence of AEs. The incidence of AEs in OFA-treated patients ranged from 85% to 89% and in the placebo group from 55% to 62.5%. Thus, AEs occurred with a numerically but not significantly higher frequency in patients treated with OFA. SAEs occurred in 3.7%, 5%, 9.4%, 9.5%, 13%, and 20% of the OFA-treated patients compared with 0%, 0%, 3%, 5%, and 7% of the placebo treated-patients. Only one death was reported (interstitial lung disease) occurring in a patient that received 700 mg OFA.

Health-related QoL was assessed in the study of Taylor et al. (47) using scoring by FACIT-F and version 2 of the 36-Item Short Form Health Survey. For both scores significant improvements were seen in OFA-treated patients (47).

Synopsis: Available results show that OFA in combination with methotrexate is more effective than placebo treatment. There were no safety concerns. However, results from SC administered OFA are sparse and need further investigation.

One study matched our inclusion criteria assessing OFA in SLE patients with refractory lupus nephritis (48). It was a case series including four patients with initial response to RTX, however, during the course of RTX treatment, patients had developed infusion reactions and were thus treated with OFA.

IV OFA was administered at different dosing regimens. All patients received prednisolone as concomitant treatment. One patient was additionally treated with cyclosporine A and another with antimalarial drugs. No primary nor secondary endpoints were defined.

The efficacy of OFA treatment was assessed using the urine albumin-to-creatinine ratio. Although it decreased in all four patients, only one reached normalization.

The only observed AE occurring in one patient one day after OFA infusion was widespread urticaria, which caused discontinuation of OFA in that patient.

The influence on their QoL was not assessed.

Synopsis: Available results are sparse but indicate a treatment effect in SLE patients with lupus nephritis. However, RCTs involving more patients are needed to confirm these initial findings.

We found one study assessing UBL in 48 patients with relapsing-remitting MS, as defined by the 2010 McDonald criteria (49). Patients were randomized to receive either placebo (12 patients) or UBL (36 patients), within six cohorts treated with different doses (450 mg or 600 mg) given over 1–4 hours of infusion. The study was unblinded on day 28 and patients in the placebo group could cross over to the corresponding treatment group.

The primary endpoint, CD19⁺ B cell depletion of at least 95%, was achieved in all patients receiving UBL. In most patients CD19⁺ B cell depletion was achieved within 24 hours after the first dose of UBL and was maintained for up to 48 weeks. No new or persisting GdE T1 lesions were observed, however, 8 patients developed one or more new GdE T2 lesions. 93% of all patients remained relapse-free, and, overall, 74% had no evidence of disease activity.

UBL was well tolerated, with infusion-related reactions representing the most common AEs. There was only one SAE observed. No deaths were reported.

Synopsis : UBL was well tolerated and resulted in a significant reduction of circulating CD19⁺ B cells and a reduced annualized relapse rate of MS. However, the included number of patients was too small to conclude. Moreover, future studies should compare UBL to established treatments of MS.

One phase I open-label study tested UBL in patients with neuromyelitis optica spectrum disorder (NMOSD) (50). 5 patients with NMOSD and new neurological symptoms received an IV infusion of 450 mg UBL in addition to standard treatment with IV methylprednisolone.

The primary endpoint was safety. Secondary endpoints included efficacy and assessment of B cell counts. Efficacy was assessed by measuring the EDSS score at baseline, during relapse, at discharge, and at a 90-day follow-up visit. Overall, EDSS increased from 4.0 at baseline to 6.5 during relapse and remained high until discharge. However, it returned to 4.0 at the 90-day follow-up visit.

Only one patient experienced a SAE, which was leukopenia without corresponding symptoms or complications.

Synopsis : This small phase I study using UBL in NMOSD patients showed promising safety results. However, the currently available data on the efficacy of UBL in NMOSD are sparse and need further assessment in RCTs.

We identified two clinical trials conducted as open-label studies without control group matching our inclusion criteria (51, 52). The study durations were 48 weeks (51) and five years (52).

91 patients were treated with VEL during either of the two trials. Patients needed to have a diagnosis of primary immune thrombocytopenia (ITP) according to the American Society of Hematology guidelines with a platelet count <30 x 10⁹ g/L on two separate occasions to enter the study. Marked or major bleeding were exclusion criteria.

VEL was either given IV (51) or SC (51, 52). All but one treatment arm, which received weekly VEL, was treated with two doses given two weeks apart. Single doses ranged from 80 to 320 mg. One study permitted the concomitant use of prednisone and danazol if given at stable doses (51), whereas a second trial only allowed concomitant prednisone (52). Before IV administration, antipyretics and antihistamines were given as premedication.

Both studies had no predefined primary endpoint. However, studies were planned to determine safety, efficacy, pharmacodynamics, pharmacokinetics, and immunogenicity.

Efficacy was assessed through objective response, corresponding to a platelet count of ≥30 x 10⁹ g/L measured twice at least one week apart with at least two-fold increase from baseline count, and complete response, corresponding to a platelet count of ≥100 x 10⁹ g/L. Of the IV treated patients 67% achieved an objective response with 33% complete responders. SC administration led to 53% and 49% objective responses and 28% and 32% complete responses in the two studies, respectively. Median time to relapse was eight months (51) and 1.3 years (52), respectively. One study also reported a bleeding reduction in all treatment groups (52).

71.4% of the IV VEL-treated patients had at least one treatment-related AE, whereas 73.5% and 78% of the SC groups had at least one AE. A total of two SAEs occurred, one in a SC treated patient (grade 3 viral gastroenteritis) and one in a patient receiving IV VEL (grade 3 hypersensitivity reaction).

Neither of the studies assessed QoL.

Synopsis: Available efficacy results of VEL treatment of 91 patients suffering from primary ITP seemed promising, with no unexpected safety events. However, both studies were conducted as open-label uncontrolled trials making the available data rather unreliable. Thus, blinded RCTs need to verify the results reported above.