As a result, eight studies could be identified that suited the aim of this review. One of the trials had been conducted in the United Kingdom, one in Turkey, one in Egypt, one in China, and four in Germany. The publications had been released between 2000 and 2012 and concerned a total of 642 patients, 281 of whom had been treated with AWB. The times of administration of intramuscular AWB varied between three and ten injections once to thrice weekly, the dosage between one and five milliliters.
Four controlled trials were devoted to the treatment of urticaria. The other four RCTs concerned each one a different indication, including atopic dermatitis, ankylosing spondylitis, treatment of common cold and prevention of recurring respiratory tract infections.
Efficacy of AWB
Five RCTs found no statistical difference between the groups, including four of the five larger RCTs. One of these, a non-blinded trial about the prevention of recurring respiratory tract infections [
2], used as control instead of Placebo Engystol® (Biologische Heilmittel Heel GmbH, Baden-Baden, Germany), a homeopathic remedy made of sulfur and white swallow-wort (
Vincetoxicum hirundinaria) which is used for the prevention of common cold and has antiviral properties in vitro [
20]. As two treatments with possible but unclear efficacy were compared in this trial no conclusion on efficacy of AWB therapy can be drawn from it.
Another one of these RCTs compared AWB with autologous serum injections for chronic urticaria in 30 ASST-positive patients and found no statistical difference between the groups either [
14]. The treatment was administered once weekly for 8 weeks (2,5 ml at the first, 5 ml in subsequent treatments). Outcome measure was the Urticarial Total Severity score (TSS). The difference between the mean TSS at baseline and in week 8 as well as week 12 was highly significant in both groups (
p < 0,01). Because again two treatments with possible but unclear efficacy were compared in this trial no conclusion on efficacy of AWB therapy can be drawn from it.
Also, a RCT investigating AWB therapy in patients with ankylosing spondylitis found no significant difference between verum and control group [
18]. In the double-blinded trial 1 ml AWB mixed with 1 ml
Formica rufa 6x was injected intramuscularly twice weekly for 4 weeks. The control group was treated in the same frequency and application mode with 1.5 ml sodium chloride 0.9% solution. This trial was effected in a rehabilitation facility. All patients of both groups underwent in parallel an intensive therapeutic training scheme of 4 weeks. Both, verum and control group showed an improvement of symptoms. An additional effect of AWB mixed with
Formica rufa could not be detected. The use of AWB and
Formica rufa 6x injections as an adjunct to an effective therapeutic training program blurs the statistical analysis, so that efficacy of the injections cannot be estimated.
The fourth of the RCTs showing no statistical difference between verum and control group was effected by Gündling et al. about the treatment of common cold [
15]. The trial was double-blinded, in the verum group 2 ml of AWB were administered thrice weekly. The control consisted in the application of the same amount of sodium chloride solution, also thrice weekly. Only 10% of the patients who were asked agreed to participate in the trial and the rate of discontinuing patients was high. Reasons for patients to refuse to participate might be due to the time-consuming treatment and the declination of intramuscular application of Placebo. The authors admit that these factors might have led to a selection of the patient sample. Otherwise, this study was well designed, reached the maximum Jadad score (Table
1) and was valid. Common cold can, therefore, not be regarded as promising indication for further studies with AWB therapy.
The last of the RCTs showing no statistical difference between AWB and Placebo group included 88 patients, but as these were split into six groups, the trial must still be considered within the scope of a pilot study [
16]. Kocatürk et al. submitted patients with ASST-positive
1 and ASST-negative urticaria to AWB, autologous serum and Placebo injections.
Three controlled trials reported a statistically significant effect of AWB compared with the control group. Pittler et al. presented a pilot RCT about efficacy of AWB injections in atopic dermatitis [
3]. The study was well designed and showed beneficial effects in the verum group. However, the authors suggest that the treatment period of 5 weeks might not have been long enough to show the full potential of AWB injections, seeing as the improvement in the verum group was more pronounced towards the end of the treatment and especially towards at the end of week 9.
A larger dimensioned controlled trial [
17] studied efficacy of AWB injections combined with traditional Chinese medicine and Western medicine in patients with chronic urticaria. One hundred fifty-seven patients were divided into three groups. One group was treated with traditional Chinese herbs, the other with Western medicine, consisting in antihistamines, vitamin c, and calcium. The third group received both traditional Chinese and Western medicine with additional AWB injections, diluted with sterile water and lidocaine, every 3 days for a period of 24 days in both buttocks. In the AWB group, 29 out of 52 patients were considered healed after the treatment, whereas in the TCM group 9 out of 52 and in the western medicine group 8 out of 53 showed no further symptoms. In the AWB group, only one out of 52 patients showed no improvement, whilst in the TCM group 13 out of 52 and in the Western medicine group 15 out of 53 patients did not report any change compared with baseline. As there was no control group combining TCM and Western medicine, the effectiveness of AWB injections cannot be estimated by this trial.
The third RCT with reported beneficial effects of AWB therapy was conducted single-blinded and Placebo controlled with sample sizes between 9 and 16 individuals per group comparing ASST-positive and ASST-negative urticaria patients [
19]. The data showed a tendency for ASST-positive patients to benefit from AWB injections, whereas no difference between AWB and Placebo could be noted in ASST-negative patients. No significant differences in the level of FcεRI-targeting autoantibodies or of IgE could be noted between ASST-positive and ASST-negative patients, so that this study supplied no clue as to the effector mechanisms of AWB in urticaria.
Three of the four urticaria trials used the same dosage and frequency of AWB injections. Two RCTs with Placebo as control found a better response to AWB in ASST-positive patients [
16,
19]. One small RCT [
14] examined the difference in the efficacy of AWB and autologous serum in ASST-positive patients, which both showed equally good results.
All in all, four out of eight controlled trials used inadequate, that means potentially active controls (autologous serum injections [
14], homeopathic injections [
2], training schedules [
18], Traditional Chinese Medicine, Western Medicine [
17]). These study designs do not allow a statement about the efficacy of AWB, neither in the positive nor in the negative.
In the other four out of eight controlled trials, Placebos were used as controls. Two of the Placebo controlled trials showed no statistical difference [
15,
16], while two others reported superior results of AWB [
3,
19].
An overview of methods and results of all studies is displayed in Table
2.
| Chronic autoreactive urticaria | 30 ASST+ (15 AWB, 15 AS) | RCT: AWB vs. AS, not blinded | 8 weeks | 1x/w; AWB: 1st injection 2.5 ml, following 5 ml; AS: 2 ml every time | AWB: p < 0.01 (weeks 8 + 12) AS: p < 0.01 (weeks 8 + 12) No statistical difference between treatments | |
Hensler, Gündling et al. [ 15] | Treatment of Common Cold | 114 (58 AWB, 56 Placebo) | RCT: AWB vs. Placebo double-blinded | 1 week | 3x/w 2 ml | No statistical difference | |
Jobst, Altiner et al. [ 2] | prevention of recurring respiratory tract infections | 75 (38 AWB, 37 Engystol®) | RCT: AWB vs. Engystol®, not blinded | 5 weeks | 2x/w 3 ml | No statistical difference between AWB and Engystol® | |
| Urticaria | 88 (ASST+ 59: 20 AWB, 20 AS, 19 Placebo; ASST- 29: 9 AWB, 10 AS, 10 Placebo) | RCT: AWB vs. AS vs. Placebo, single-blinded | 10 weeks | 1x/w; 1st injection 2.5 ml, following 5 ml | No statistical difference | |
| Chronic Urticaria | 157 (52 AWB, TCM (Chinese Herbs) + Western Medicine, 53 Western Medicine, 52 TCM) | Controlled trial: AWB + TCM + Western Medicine vs. TCM vs. Western Medicine, not randomized, not blinded | 24 days | Every 3 days (total of 8 injections) 5 ml AWB + 1 ml lidocaine + 4 ml H2O, each side 5 ml | Treatment group (AWB + TCM + Western Medicine) more effective than the other groups (p < 0.05) | |
Pittler, Ernst et al. [ 3] | Atopic Dermatitis | 30 (15 AWB, 15 Placebo) | RCT: AWB vs. Placebo, double-blinded | 5 weeks | 1x/w; 1–2 – 3 – 2 – 1 ml | SASSAD score: week 5 P = 0.001 week 9 P < 0.001 patient’s statement: no statistical difference | |
Schirmer, Fritz, Jäckel [ 18] | Spondylitis ankylosans | 100 (51 AWB + Formica, 49 Placebo) + training scheme (both groups) | RCT: AWB + Formica vs. Placebo double-blinded | 4 weeks | 2x/w 1 ml AWB + 1 ml Formica rufa 6x | No statistical difference | Trial effected in rehabilitation facility |
Staubach, Onnen et al. [ 19] | Chronic Urticaria | 48 (29 ASST+: 13 AWB, 16 Placebo, 19 ASST-: 10 AWB, 9 Placebo) | RCT: AWB vs. Placebo, single-blinded | 8 weeks | 1x/w; 1st injection 2.5 ml, following 5 ml | ASST+ patients: AWB UAS −41%, p < 0.05, wheals duration + size −46%/−48%, p < 0.05, erythema −56%, p < 0.05, DLQI week8 + 70%, p < 0.005, week12 + 66%, p < 0.05, antihistamines −52%, p < 0.05; Placebo UAS −18%; ASST- patients: AWB UAS −21%, Placebo UAS −11% | |