Allergen-AntibodyActa Derm Venereol (Stockh) 1992; Complexes Suppl. 176: 129--131 in the Treatment of Atopic Dermatitis: Preliminary results of a double-blind placebo-controlled study

1 1 2 1 BERNARD1 P. LEROY • GRlET BODEN • MARC G. JACQUEMlN l• JEAN-MARIE LACHAPELLE de Dermruologie Professionndle Envi.ronnemem, Cinical Jmmwwl lnstillue of Cell11lar and Mo/ecu/ar and JEAN MARIE R. SAINT-REMYet 1 ogy Parhology. Caiholu,ue de Louvain, Brussels, Belgium Unite de I' arui ! Alle11fyQfld Uni1; Univusile Twenty-three adult patients suffering from chronic atopic der­ the matitis (AD) have been treated by regular injections of com­ plexe.� made of D. pteronyssinus allergens and specific autolo­ Encouraged by results obtained in aUcrgic bronchial antibodies. double-blind. ,placebo-controlled protocol asthma we have conducted an open trial in aduJt AD. and have foUowed for months, then the patients were treated shown a rapid and sustained improvcment in tbe clinical condi­ openlygous to completeA a full :year on active therapy. Preliminary tion of the patients (6). A double-blind placcbo-controlled was 4 results are presented for the months. Seventy-three study was therefore initiated, whose preliminary resuJts are percent of patients improved when treated with complexes, reported here. showing a mean improvementfirst 8 tban after months. This study injectionsof allergen-antibody of more 70% 4 Parilllls complexes is an etTective treatment least some forms MATERIAL AND METHODS and confirms that airbornesuggests allergensthat are significant exacerbat­ of at of AD f ing f.actors AD. Key words: Atopic dermatitis; Twemy-three adult patients, aged 15 to 64. sufering from severe AD therapy; D. pteronyssi,ms. nmuno­ in of b participated in this study. The diagnosis of AD was established accord­ ing to Hanifin & Rajka's criteria but. addition, the patieatsIU/mJ). had evidenceof sensitization to Dpt (high leve I of spocific lgE to 0pt) and Acta Derm Venereol (Stockh) 1992; Suppl. 176: 129-131. elevated titres of total lgE antibodies (greater tllan 200 The mean duration of AD was 26 years and an average of 71 % of the body J. M. R. Saint-Remy, Allergy and Clinical Immunology Unit, surface area was affected by skin lesions. Fifty-six percent of tbe ICP 7430. 74 Avenue Hippocrate, 1200 Brusscls, Belgium. patientsdesign also suffcred from allergic bronchial asthma.

Swdy Clinical evidence has recently emerged(AD) showing that at least The patient population was randomly allotted to two groups: Group A some forms of atopic dermatitis can be exacerbated with 12 patients who were actively treated by injection5 of allergen­ antibody complexes from the start of the study. and Group B, desig­ when the patient is exposed to airborne allergens, such as nated as placebo group, with the rcmaining 11 patients. The study those contained in house dust (1). Long-term avoidance from comprised lhree phascs: (1) a 4-week prc-treatment periodwbicb

130

fected. In addition, the intensity of pruritus was evaluated by the shows that most of the placebo effect was attributable to a patient using a 0-4 scale. reduction in pruritus and lichenification, which is the physical consequence of chronic scratching. RESULTS The data from 22 out of 23 patients were analysed. Sixteen DlSCUSSION patients (73%) showed a clinical improvement as a rcsult of injection of allergen-antibody complexes. Fig. 1 shows the These preliminary data show that injections of allergen-anti­ evolution of the disease intensity score for these 16 patients body complexes in adult patients suffering from AD can pro­ over the first 8 months of the study. In order to dcal with foundly improve thc clinical condition in a majority of cases. inter-individual variations, a mean of the three clinical evalu­ The number of patients treated so far is, however, too small to ations made during the 4-week pre-treatment period was taken decide whcther a comparable improvement could be obtained as baseline value, which was then ·normalized' to 1,000. Fig. l in a majority of AD patients. or whether the patients treated shows that: (1) group A patients bcgan to improve shortly here represent a particularly responsive subgroup of patients. after the start of the injection schedule; 50% improvement was However, it should be noted that the criteria used to select the obtained af ter 9 weeks of therapy, 72% by the end of the patients, namely, confimed diagnosis of AD coupled with fourth month and 85% after 8 months; (2) group B patients evidence of sensitization to Dpt and high levets of total IgE also improved during the first weeks, but then rapidly deterio­ antibodies, are by no means restrictive, insofar as most AD rated, to resume their initial intensity scores at the end of the patients have serological evidence of Dpt sensitivity. fourth month; (3) on active thcrapy, group B patients showed It also remains to determine whether the long-term fol­ a rapid and sustained improvement, which reached 71 % at the low-up of these patients will confirm the benefit of such ther­ end of the eighth month of the study. apy. The evolution of patients treated by allergen-antibody Table I shows the evolution of pruritus and of individual complexes in thc first open trial we (manuscriplconducted (6)submiued). already clinical symptoms during the first 8 months of therapy. The indicates a sustained improvement for at least 2 years in an pcrcentages of reduction in severity vis-a-vis the baseline val­ overwhelming majority of patients ues are also given (italics). This indicates that the clinical Whether or not any significant alteration of the immune re­ evolution was the result of an overall improvement in both sponse to Dpt accompanies the clinical changes is currently acute and chronic signs of AD, together with pruritus. It also under investigation.

1200 l

c,: 1000

KIX)

� Cl>.. 600 � ·;;; C 400 C

200

()+ -,--,-..--,--,,.....,-,.--,---,,---,--,--,--,-..--,--,,.....,-,.--,-...,...... ,...... ,....-,--,--,-..--,--,,.....,-, Fig. I. 0 6 8 10 12 16 I 8 20 22 24 26 28 31 2 4 Evolution of AD□ .intensity score during the Wttks first 8 months of allergcn-antibody complcx thcrapy: .& .group A; group B; vertical range bars represent SEM. Acta Derm Venereo/ (Stockh) 71 Allergen-antibody complex treatment of AD 131

Tablc C/inical symptoms of AD evaluated prior lo /rea/ment and after 4 and 8 months of allergen-antibody complex therapy.

I. Mean score (% change from baseline)

Week 0 Week 16 Week 32

Bascline score Mcan score % red Mean score % red

Group A Pruritus 3.25 2.18 33 1.39 57 Erythema 4.12 2.35 43 2.14 48 Ederna 3.75 1.54 59 1.42 62 Papulation 2 62 1.2 54 0.86 67 Excoriations 3 1.77 41 1.11 63 Lichenification 3.5 1.89 46 0.98 72 Desquamation 3 1.68 44 1.44 52

Activc therapy

Group 8 Pruritus 3.25 2.6 19 1.9 41 Erythema 4.25 4.16 2 3.06 28 Ederna 4.12 3.83 7 2.27 45 Papulation 3.87 3 89 0 0.81 79 Excoriations 3.12 2.87 8 l.22 61 Lichenification 4.12 2.8 32 1.73 58 Desquamation 2.25 2.25 0 2.18 3

Active therapy

SR. The role of dust mite allergens in atopic dcrmatitis. Clin Exp Dermatol 1983; 8: 233-247. ACKNOWLEDGEMENT 3. Arlian LG. House dust mite allergens: a review. Experimental & The authors thank Therese Briet and Monique Schroeder for excellent Applied Acarology 1991; 10: 167-186. technical assistance, Alan Barclay for reviewing the typescript and 4. Machiels JJ. Somville MA. Lebrun PM. Lcbccque SJ. Jacquernin Brigitte Firkct for secretarial help. MG, Saint-Remy JMR. Allergic bronchial asthma due to D. ptero­ nyssinus hyperscnsitivity can be efficiently treated by inocula1ion of allcrgen-antibody complexes. J Ciin lnvest 1990; 85: 1024-1035. 5. Blaser K, de Weck AL. Regulation of the lgE antibody response by I. Adinoff AD, Tellcz P. Clark RAF. Atopic dcrmatitis and aero­ idiotype-anti-idiotype network. Progr Allergy 1982; 32: 203-264. REFERENCESallergen contact sensitivity. J Allergy Clin lmmunol 1988; 81: 736- 6. Leroy B, Lachapellc JM, Somville MM, Jacquemin MG. Saint­ 742. Rcmy JM. lnjection of allergen-antibody complcxes is an effective 2. Plans-Milis TA, Mitchell EB, Rowntree S, Chapman MD, Wilkins treatrnent of atopic dermatitis. Dermatologica 1991; 182: 98-106.

Acta Dem, Venereol (Stockh) 71

9•