Guidelines for Using Antipruritic Drugs in Dogs

Guidelines for Using Antipruritic Drugs in Dogs: Comparison

Please note this is a comparison between Version 2 by Beatrix Zheng and Version 1 by Marie Christine Cadiergues.

Pruritus is defined as an unpleasant sensation that provokes the desire to scratch. Pruritus is a common clinical sign of many skin disorders and is the most common complaint in canine dermatology. Pruritic skin diseases can affect the quality of life (QoL) of dogs and their owners. The first indication for the use of antipruritic drugs is, of course, allergies, notably canine atopic dermatitis (AD). However, in pruritic infections or parasitic dermatoses, the speed of action and the level of efficacy of etiological treatments vary and, to improve the QoL of both the dog and the owner, the use of an additional symptomatic antipruritic drugs in addition to etiological treatment sometimes makes sense after obtaining a clear diagnosis.

dog
pruritus
allergy
atopic dermatitis
glucocorticoids
antihistamines
ciclosporin
oclacitinib
lokivetmab

1. Introduction

The most common causes of pruritus are allergies, parasites and bacterial or fungal infections. Diagnosis requires a methodical workup, and successful treatment depends on the identification of the underlying causes. Antiparasitics, antibiotics and/or antifungals are the first step in the control of pruritus. The high prevalence of pruritus and its impact on animals should encourage veterinarians to carefully consider the appropriate symptomatic treatment. In 2007, in humans, members of the International Forum for the Study of Itch proposed an etiological classification of pruritus [3]. An adaptation of this classification for dogs was recently proposed, with six distinct origins: dermatological, systemic, neurological, psychogenic, mixed, and other [4]. The aim of this article is to guide the practitioner in the choice of the most appropriate symptomatic antipruritic in the most frequent situations of dermatological pruritus.

1. Introduction

The most common causes of pruritus are allergies, parasites and bacterial or fungal infections. Diagnosis requires a methodical workup, and successful treatment depends on the identification of the underlying causes. Antiparasitics, antibiotics and/or antifungals are the first step in the control of pruritus. The high prevalence of pruritus and its impact on animals should encourage veterinarians to carefully consider the appropriate symptomatic treatment. In 2007, in humans, members of the International Forum for the Study of Itch proposed an etiological classification of pruritus ^[1]. An adaptation of this classification for dogs was recently proposed, with six distinct origins: dermatological, systemic, neurological, psychogenic, mixed, and other ^[2].

Antipruritic management is a multi-faceted approach that includes etiological, topical, and systemic symptomatic treatment. Even if topical treatments such as shampoos and emollients are helpful [5,6], this review only focuses on the main systemic and topical molecules with a veterinary drug registration and market authorization with antipruritic and/or antiallergic indications in Europe: glucocorticoids, antihistamines, ciclosporin, oclacitinib, and lokivetmab.

Antipruritic management is a multi-faceted approach that includes etiological, topical, and systemic symptomatic treatment. Even if topical treatments such as shampoos and emollients are helpful ^[3][4], this entry only focuses on the main systemic and topical molecules with a veterinary drug registration and market authorization with antipruritic and/or antiallergic indications in Europe: glucocorticoids, antihistamines, ciclosporin, oclacitinib, and lokivetmab.

Different methods of synthesizing information and confronting conflicting opinions can be used [7]. Because of the absence or the paucity of literature with a high level of evidence, for this review, the seven experts used the consensus development conference leading to formalized consensus guidelines (not clinical practice guidelines) [7]. The experts conducted a critical analysis of the literature and formulated their recommendations. A minimum agreement among six out of the seven experts (>80%) was chosen to represent a consensus.

Different methods of synthesizing information and confronting conflicting opinions can be used ^[5]. Because of the absence or the paucity of literature with a high level of evidence, for this research, the seven experts used the consensus development conference leading to formalized consensus guidelines (not clinical practice guidelines) ^[5]. The experts conducted a critical analysis of the literature and formulated their recommendations. A minimum agreement among six out of the seven experts (>80%) was chosen to represent a consensus.

2. Recommendations

The results are summarized in

Table 8 and

1 and

Table 9.

Table 81.

Summary of antipruritic drugs that may be used, according to the clinical situation.

Clinical Situation		Molecules That Can Be Recommended

Dog with atopic dermatitis

During flares

The strength of recommendation (SoR) was ranked as follows ^[6]: A—recommendation based on consistent and good-quality patient-oriented evidence; B—recommendation based on inconsistent or limited-quality patient-oriented evidence; C—recommendation based on consensus, opinion, case studies, or disease-oriented evidence.

Table 92.

Summary of antipruritic drugs that may be used in atopic dogs with co-morbidities.

Type of Co-Morbidity	Antipruritic Drug That Can Be Recommended and SoR	¹
liver disorder	(reactive therapy)	oral glucocorticoids ((SoR A))	¹	topical glucocorticoids (mainly hydrocortisone aceponate) (SoR C) antihistamines (SoR C) topical glucocorticoids ((SoR C)) antihistamines (mild AD flares) ((SoR C)) oclacitinib (SoR A) lokivetmab (SoR A)
oclacitinib (SoR C)		In non-flares periods (proactive therapy)	topical glucocorticoids (SoR A) antihistamines (SoR B) ciclosporin (SoR A) oclacitinib (SoR A) lokivetmab (SoR A)
renal disorder
lokivetmab (SoR C)
lokivetmab (SoR C)	topical glucocorticoids (mainly hydrocortisone aceponate) (SoR C) antihistamines (SoR C) ciclosporin (SoR C) oclacitinib (SoR C) lokivetmab (SoR C)	With superficial pyoderma or microbial overgrowth	Antihistamines (SoR C) ciclosporin (SoR C) oclacitinib (SoR C) lokivetmab (SoR C)
diabetes mellitus	topical glucocorticoids (hydrocortisone aceponate) (SoR C) antihistamines (SoR C) oclacitinib (SoR C) lokivetmab (SoR C)	During the induction period of ASIT	oral glucocorticoids (SoR B) topical glucocorticoids (SoR C) antihistamines (SoR C) oclacitinib (SoR C) lokivetmab (SoR C)
neoplastic diseases	topical glucocorticoids (hydrocortisone aceponate) (SoR C) antihistamines (SoR C) oclacitinib (SoR B) lokivetmab (SoR C)	During allergologic tests	oral glucocorticoids (serological tests only) (SoR B) antihistamines (serological tests only) (SoR A)	During dietary trials
urinary infections	ciclosporin (SoR B) oclacitinib (SoR C) oral glucocorticoids (SoR C) topical glucocorticoids (SoR C) antihistamines (SoR C) oclacitinib (SoR C)
In pruritic ectoparasitic dermatoses		oral glucocorticoids (short course) (except demodicosis) (SoR C) antihistamines (SoR C) oclacitinib (except demodicosis) (SoR C) lokivetmab (SoR C)

¹ The strength of recommendation (SoR) was ranked as follows [8]: A—recommendation based on consistent and good-quality patient-oriented evidence; B—recommendation based on inconsistent or limited-quality patient-oriented evidence; C—recommendation based on consensus, opinion, case studies, or disease-oriented evidence.

oral glucocorticoids (occasional urinary tract infections) (SoR C)

topical glucocorticoids (hydrocortisone aceponate) (SoR C)
	antihistamines (SoR C) ciclosporin (occasional urinary tract infections) (SoR B) oclacitinib (occasional urinary tract infections) (SoR B) lokivetmab (SoR C)

¹ The strength of recommendation (SoR) was ranked as follows [8]: A—recommendation based on consistent and good-quality patient-oriented evidence; B—recommendation based on inconsistent or limited quality patient-oriented evidence; C—recommendation based on consensus, opinion, case studies, or disease-oriented evidence.

2.1. Systemic Glucocorticoids

2.1.1. In Atopic Dogs, excluding the Induction Period of ASIT

During Flares (Reactive Therapy)

Oral glucocorticoids (prednisolone, methylprednisolone (SoR A), prednisone (SoR B) and injectable dexamethasone (SoR C) are effective for the treatment of flares of canine AD. They can be administered initially at 0.5–1.0 mg/kg (prednisolone) or 0.4–1 mg/kg (methylprednisolone) per day (SoR A), in one or divided into two administrations (SoR A), using a dose that is maintained or that can be decreased after 3–7 days (SoR B) using either a standard protocol or based on the outcome (SoR B). A significant reduction in pruritus is obtained rapidly, in a few hours or in a few days (SoR B).

In Non-Flare Periods (Proactive Therapy)

No data are available. Use of systemic glucocorticoids for long-term management of canine AD is not recommended (SoR C) or only with great care, if a low dose (SoR C) is administered at 48 or 72 h intervals. Adrenal insufficiency can be minimized by instituting therapy eod, but adrenal insufficiency may occur at any pharmacologically active dose. Adrenal insufficiency may be particularly obvious after the discontinuation of corticosteroid therapy. Dose reduction and discontinuation should be gradual to avoid precipitating adrenal insufficiency even temporarily (SoR C).

Adverse events are frequent in short-term treatments and mainly consist of polyuria, polydipsia, polyphagia (SoR A) and gastrointestinal disorders (SoR B).

In Dogs with Superficial Pyoderma or Microbial Overgrowth

Few data are available. Daily oral administration of 0.75 mg/kg prednisolone for one month did not alter the skin microbiome of six asymptomatic atopic dogs [118]. Nevertheless, considering their potential pro-infectious characteristics, their use should be restricted in the case of secondary skin infections and infectious diseases (SoR C).

In Dogs with Specific Problems

Liver disorders

Changes in liver parameters associated with the use of systemic glucocorticoids are commonly observed. In the case of long-term use, their detection by regular liver function tests is recommended. The use of glucocorticoids is not recommended in animals with liver failure (SoR C).

Renal disorders

The use of glucocorticoids is not recommended in dogs with renal disorders (SoR C).

Diabetes mellitus

Glucocorticoids stimulate gluconeogenesis. Lipogenesis is enhanced in certain areas of the body and adipose tissue may be redistributed away from the extremities to the trunk (SoR C). The use of glucocorticoids is associated with an increase in serum insulin but not serum fructosamine concentrations in dogs with canine AD (SoR B). Since prolonged use of systemic glucocorticoids can lead to the development of diabetes, their use in a diabetic animal, even if controlled, is not recommended (SoR C).

Neoplastic diseases

Long-term use can cause immunomodulation that can lead to the development of neoplasia (SoR C). The use of glucocorticoids is not generally recommended in dogs with cancers (SoR C) unless they are part of the chemotherapy regimen [119,120].

Urinary infections

Routine urine cultures and assessment of bacteriuria by cystocentesis should be part of the monitoring for dogs on long-term glucocorticoids. Glucocorticoids should be used cautiously in dogs with occasional urinary tract infections and be avoided in dogs with recurrent urinary infections (more than two episodes in six months or more than three episodes per year) (SoR C) [121].

2.1.2. In Atopic Dogs, during the Induction Period of ASIT

Systemic glucocorticoids can be used during ASIT (SoR B) and can be used in the case of an adverse event during ASIT rush therapy (SoR B).

2.1.3. In Atopic Dogs, during Allergy Testing

Systemic glucocorticoids do not interfere with specific allergen serology tests (SoR B). They should be stopped at least two weeks prior to IDST as they can interfere with cutaneous reactions (SoR B).

2.1.4. In Atopic Dogs, during Dietary Trials

Systemic glucocorticoids can be used during the initial period of an elimination diet (SoR C).

2.1.5. In Pruritic Ectoparasitic Dermatoses

No data are available. Long-term use may indirectly promote parasitic infestation while masking or reducing symptoms. With the exception of demodicosis (confirmed or previous), for which glucocorticoids should be avoided, a short course (five days maximum) of oral glucocorticoids would be acceptable when initiating the treatment of a highly pruritic sarcoptic mange, flea infestation or flea allergy dermatitis (SoR C).

2.1.6. With Vaccines

In the case of vaccination with live attenuated vaccines, an interval of two weeks should be observed before or after treatment (SoR C). In the guidelines for the vaccination of dogs and cats published in 2016, experts reported the suggestion that immunosuppressive glucocorticoid treatment, i.e., with higher doses than for allergic diseases, prior to or concurrently with vaccination, has no significant suppressive effect on antibody production in response to vaccines. However, revaccination is recommended two or more weeks after glucocorticoid therapy has ended, especially when treatment occurs during the administration of the initial series of core vaccines [122].

2.2. Topical Glucocorticoids

2.2.1. In Atopic Dogs, excluding the Induction Phase of ASIT

During Flares (Reactive Therapy)

Topical glucocorticoids (hydrocortisone aceponate (SoR C), triamcinolone (SoR C)) are effective for the treatment of flares of canine AD, especially for localized lesions. At the time of writing (2022), the lack of data on the efficacy of topical glucocorticoids in the first two weeks of treatment does not allow a recommendation beyond SoR C. The optimal regimen is daily treatment followed by a reduction in the frequency of application on the skin based on outcome (SoR C).

In Non-Flare Periods (Proactive Therapy)

The use of triamcinolone is also possible and effective, although there may be an increase in side effects (SoR B). With the use of other topical glucocorticoid formulations, there may be variations in efficacy and safety depending on the strength of the glucocorticoid, the chemical structure, and the vehicle [123,124]. Most topical corticosteroids are absorbed in quantities that can produce both systemic and local adverse effects [125]. These marked adverse effects may be observed with prolonged or frequent use and are more rapidly observed, more frequent, and more severe with potent topical corticoids (SoR C).

In Dogs with Superficial Pyoderma or Microbial Overgrowth

No data are available but, for the same reasons as systemic corticosteroids, it is not recommended to use topical glucocorticoids in the case of secondary skin infections and infectious diseases (SoR C).

In Dogs with Specific Problems

Liver disorders

No data are available but as hydrocortisone aceponate does not cause changes in biochemical parameters, this molecule could be used in dogs with liver disorders (SoR C). Caution is required with other topical glucocorticoids (SoR C).

Renal disorders

No data are available. Hydrocortisone aceponate does not cause changes in renal parameters so this molecule could be used in dogs with renal disorders, but regular biochemical tests are mandatory (SoR C).

Diabetes mellitus

No data are available. Due to its mode of action, hydrocortisone aceponate could be used in dogs with diabetes mellitus, but regular biochemical tests should be performed (SoR C). Like with other topical corticoids, there is a risk of developing diabetes mellitus as in humans with the cumulative dose and cumulative duration of use (SoR C) [126].

Neoplastic diseases

No data are available. Hydrocortisone aceponate could be used in dogs with neoplastic diseases after evaluation of the benefit/risk ratio by the responsible veterinarian (SoR C).

Urinary infections

No data are available. Because of its mode of action, hydrocortisone aceponate could be used in dogs with urinary infection (SoR C).

2.2.2. In Atopic Dogs, during the Induction Phase of ASIT

No data are available, but topical glucocorticoids can be used during the induction period of ASIT (SoR C).

2.2.3. In Atopic Dogs, during Allergy Testing

Hydrocortisone aceponate and other topical glucocorticoids should be stopped at least two weeks prior to IDST as they can interfere with the cutaneous reactions (SoR B) [127,128]. No data are available but topical glucocorticoids should not interfere with specific allergen serology tests (SoR C).

2.2.4. In Atopic Dogs, during Dietary Trials

No data are available, but topical glucocorticoids can be used at the beginning of trials for localized lesions to relieve the animal (SoR C).

2.2.5. In Pruritic Ectoparasitic Dermatoses

Topical glucocorticoids can be used when initiating treatment for flea allergy dermatitis (SoR B). With the exception of demodicosis (confirmed or previous), for which topical glucocorticoids should be avoided, a short course of treatment would be acceptable when initiating the treatment of a flea- or sarcoptic-mange-induced pruritus (SoR C).

2.2.6. With Vaccines

No data are available, but because of the absence of a systemic impact, hydrocortisone aceponate can be used (SoR C). Caution is required with other glucocorticoids, depending on their potency, especially when using live attenuated vaccines (SoR C).

2.3. Antihistamines

2.3.1. In Atopic Dogs, Excluding the Induction Period of ASIT

During Flares (Reactive Therapy)

Antihistamines are not recommended for the treatment of severe acute flare-ups of AD (SoR A). However, because their actions are animal-dependent and often mild, as they are relatively fast acting, mainly inexpensive and have few side effects, they can be used for mild AD flare-ups (SoR C).

In Non-Flare Periods (Proactive Therapy)

Limited evidence-based clinical data are available concerning the antipruritic effect of antihistamines and there is a quasi-absence of knowledge concerning the doses and frequency of administration of antihistamines in dogs. Antihistamines could have a global moderate antipruritic efficiency with individual variation (SoR B). Their use for long-term management can be tested alone in the case of mild to moderate dermatosis or associated with other molecules for any degree of severity of dermatosis (SoR C). Indeed, antihistamines can be used in a multimodal approach to reduce the dose of other drugs, such as corticosteroids (SoR C).

In Dogs with Superficial Pyoderma or Microbial Overgrowth

Antihistamines can be used in dogs with superficial pyoderma or microbial overgrowth (SoR C).

In Dogs with Specific Problems

Liver disorders

No data are available. First-generation antihistamines mainly have a hepatic metabolism. In humans, a dose reduction is recommended in the case of hepatic insufficiency, but their use is not contraindicated [129,130]. So, these molecules could be used in dogs with liver disorders, perhaps at a lower dose (SoR C).

Renal disorders

No data are available. Some antihistamines such as cetirizine have a renal metabolic route in humans, but the route is still not known in dogs [70]. In humans, in the case of renal insufficiency, a reduction in dose is recommended, but its use is not contraindicated [129,130]. Antihistamines could be used in dogs with renal disorders, perhaps at a lower dose (SoR C).

Diabetes mellitus

No data are available. Antihistamines appear to be usable in dogs with diabetes mellitus (SoR C).

Neoplastic diseases

No data are available. Antihistamines appear to be usable in dogs with neoplastic diseases (SoR C).

Urinary infections

No data are available. Antihistamines appear to be usable in dogs with urinary infections (SoR C).

2.3.2. In Atopic Dogs, during the Induction Period of ASIT

Antihistamines can be used during desensitization in dogs (SoR C).

2.3.3. In Atopic Dogs, during Allergologic Tests

A therapeutic window of seven to ten days is necessary before performing an IDST (SoR A). There have been no studies on the impact of antihistamines on serological tests. The mode of action of antihistamines should not interfere with the measurement of allergen-specific IgE. Thus, the withdrawal of antihistamines does not appear to be needed.

2.3.4. In Atopic Dogs, during Dietary Trials

No data are available. Antihistamines are not contraindicated (SoR C) [131].

2.3.5. In Pruritic Ectoparasitic Dermatoses

Antihistamines can be used in cases of mild to moderate parasitic pruritus (SoR C).

2.3.6. During Vaccines

No data are available. The summaries of product characteristics of the available formulations do not limit the use of antihistamines during vaccination. Antihistamines can be used alongside vaccines (SoR C).

2.4. Ciclosporin A

2.4.1. In Atopic Dogs, excluding the Induction Period of ASIT

During Flares (Reactive Therapy)

Ciclosporin is partially effective at the beginning of treatment, and is fully effective after four to six weeks of treatment (SoR A); it is therefore not recommended for the treatment of flares (SoR A).

In Non-Flare Periods (Proactive Therapy)

At the beginning of treatment, the combination of ciclosporin (5 mg/kg/day) and prednisolone (1 mg/kg/day for 7 days, then eod for 14 days), accelerates the clinical response with no increase in severe adverse effects (SoR B), and with a threefold greater effect on pruritus in the first few days. The authors suggest modifying the protocol by rapidly reducing the prednisolone dose to 0.5 mg/kg/d (SoR C).

EFA supplementation in the plateau stage (after two months) could improve pruritus and clinical signs (SoR B) and reduce the dose of ciclosporin (from 0.85 mg/kg/day).

Gastrointestinal side effects, most often transient and moderate, are common (46% of cases) (SoR A) [99]. Neoformations are rare (SoR A). Papillomatous lesions are reported, usually not linked to the presence of papillomaviruses, but possibly in response to bacterial infections [132]. These lesions and gingival hyperplasia usually regress after stopping ciclosporin (SoR B).

Infections were present in 11% of treated animals [133]. As the infections were mostly cutaneous (68%), it is difficult to confirm a role for the molecule given the naturally high frequency of infections during CAD and in the absence of studies with control groups [134]. Bacterial urinary tract infections (30% of infections mentioned) are neither statistically more frequent than in untreated dogs, nor are they accompanied by clinical urinary signs [98]. A link between clinical urinary bacterial infection and the use of the drug has therefore not been established, although caution is recommended and regular urinary analyses may be required during long-term treatment (SoR B).

In Dogs with Superficial Pyoderma or Microbial Overgrowth

No available information indicates any adverse effects of ciclosporin in dogs with canine AD and superficial infections, and proper management will reduce the frequency of these infections. Ciclosporin is advisable for superficial bacterial infections in dogs with well-managed canine AD (SoR C).

In Dogs with Specific Problems

Liver disorders

Ciclosporin, even when used at high doses and for long periods, does not appear to be hepatotoxic in dogs [133], but no data are available in the case of pre-existing liver disorders. The molecule does not seem to be advisable in animals with hepatic disorders because of its mainly hepatic metabolism via cytochrome P-450 [135]. However, ciclosporin seems to be beneficial to hepatocytes during porto-cavity shunting and improves hepatic biochemical parameters during chronic idiopathic hepatitis [136,137].

Ciclosporin is not recommended for liver disorders, but the benefit–risk balance should be assessed (SoR C).

Renal disorders

Unlike in humans, even when used at high doses and for long periods, ciclosporin does not appear to be nephrotoxic in dogs [133] and no adverse effects have been reported in studies on canine AD. No abnormalities in renal biochemical parameters were detected experimentally after two years of treatment in 38 dogs [87]. However, to the best of the authors’ knowledge, no studies have been conducted on animals with renal failure. Ciclosporin seems to be suitable for use in dogs with renal disorders, but the benefit–risk balance should be assessed and regular biochemical tests performed (SoR C).

Diabetes mellitus

Observations of diabetes mellitus in dogs monitored in studies are limited to one case of hyperglycemia and diabetes mellitus after three years of treatment with ciclosporin [12]. Clinical data suggest that treatment in West Highland white terriers is associated with increased incidence of diabetes mellitus [138]. Experimentally, ciclosporin may reversibly increase peripheral insulin resistance and decrease insulin secretion [139]. In a study of 16 dogs with canine AD, ciclosporin (5 mg/kg/day; six weeks) significantly increased glucose levels and decreased serum insulin concentrations, whereas fructosamine levels (statistically increased) remained within the normal range and no dog developed diabetes mellitus [93]. In diabetic dogs, the clearance of ciclosporin increased significantly and the half-life shortened compared with controls [134]. This led to the recommendation to avoid treating diabetic dogs with ciclosporin (SoR C).

Neoplastic diseases

No increase in the prevalence of neoplasia has been reported in published clinical studies. One study of 51 dogs given ciclosporin for six to 30 months did not show increased neoplasia compared with the general population [87], and ciclosporin treatment in canine AD was not a risk factor for cutaneous lymphoma [140]. No articles analyzed the effect of ciclosporin in animals with neoplastic diseases. However, the immune effects and the potential impact on tumor progression led to the recommendation to avoid using ciclosporin in dogs with neoplasia or when neoplasia is diagnosed during treatment (SoR C).

Urinary tract infections

Ciclosporin can be used in dogs with occasional urinary tract infections (SoR B) but is not recommended in dogs with recurrent episodes of bacterial cystitis (SoR C) [121].

2.4.2. In Atopic Dogs, during the Induction Period of ASIT

No data are available. An increase in the population of regulatory T cells could play a role in desensitization [141]. Ciclosporin administration increases populations of regulatory T cells in humans [142], and has no effect in dogs [143], but never reduces this population. Ciclosporin could react in synergy or have no effect on desensitization. Ciclosporin is usable during desensitization in dogs (SoR C).

2.4.3. In Atopic Dogs, during Allergologic Tests

In addition to the sole published article, one other study showed that ciclosporin reduced reactivity to the skin tests, but not the IgE assay, in relation to an Ascaris allergen [144], whereas two abstracts, one from an experimental study and the other from a clinical study, reported no effect [145,146].

Ciclosporin can be used without a therapeutic window before these sensitization tests are performed (SoR B).

2.4.4. In Atopic Dogs, during Dietary Trials

Because ciclosporin is too slow-acting to control pruritus during the induction period of a hypoallergenic diet, and because of its persistent action several days after discontinuation, potentially masking the response to the challenge diet, this molecule is not recommended during a dietary trial (SoR C).

2.4.5. In Pruritic Ectoparasitic Dermatoses

External antiparasitics are rapidly effective, whereas ciclosporin is slow, so its use is not recommended (SoR C).

2.4.6. During Vaccines

There are no published effects of ciclosporin on the efficacy and hazards of vaccination. Only indications of the summary of the product characteristics of ciclosporin-containing drugs are available: do not vaccinate with a live vaccine during treatment or in the two weeks preceding or following treatment (SoR C).

2.5. Oclacitinib

2.5.1. In Atopic Dogs, excluding the Induction Period of Allergen-Specific Immunotherapy

During Flares (Reactive Therapy)

When the molecule chosen for the control of canine AD is ciclosporin, oclacitinib can be used concomitantly at the beginning of the treatment to accelerate the reduction in pruritus (SoR B) during the flare.

Hydrocortisone aceponate can also be combined with oclacitinib to prevent the relapse of pruritus and skin lesion when reducing the frequency of administration of oclacitinib from bid to sid (SoR A).

In Non-Flare Periods (Proactive Therapy)

Oclacitinib is safe and effective and is recommended for the long-term management of canine AD (SoR A). Adverse events associated with oclacitinib are uncommon (mainly gastro-intestinal) (SoR B).

In Dogs with Superficial Pyoderma or Microbial Overgrowth

Oclacitinib could be used when dogs are affected by these infectious diseases, provided the infectious component is concomitantly—or ideally previously—controlled (SoR C). No study has shown that administration of oclacitinib aggravates the clinical signs of bacterial overgrowth, superficial pyoderma or Malassezia dermatitis. Moreover, allergic dogs treated with oclacitinib received less antibiotics than allergic dogs treated with other anti-pruritic treatments [106].

In Dogs with Specific Problems

Liver disorders

No data are available. In one case of necrolytic migratory erythema syndrome, oclacitinib was effective as long-term therapy (12 weeks) in controlling pruritus [147]. No study reported adverse hepatic effects in atopic dogs treated with oclacitinib. It thus seems that this molecule can be used in dogs with hepatic troubles, but the benefit–risk balance should be evaluated and a biochemical follow-up test conducted regularly (SoR C).

Renal disorders

No study reported adverse renal effects in atopic dogs treated with oclacitinib. It thus appears that this molecule can be used in dogs with renal troubles, but the benefit–risk balance should be evaluated and the biochemical profile checked regularly (SoR C).

Diabetes mellitus

No study reported signs of diabetes mellitus in atopic dogs treated with oclacitinib. It thus seems that this molecule can be used in dogs with diabetes mellitus, but the benefit–risk equation should be evaluated and the biochemical profile checked regularly (SoR C).

Neoplastic diseases

The summary of product characteristics prevents the use of this molecule in dogs with neoplastic diseases. The development of papilloma has also been reported in dogs. However, there is no association between the daily administration of oclacitinib and the odds of malignancies or benign skin masses [104]. Oclacitinib was a therapeutic option in one case of cutaneous epitheliotropic T-cell lymphoma [148]. Oclacitinib was well tolerated when administered in combination with carboplatin or doxorubicin in nine tumoral cases [149]. Oclacitinib was shown to modulate the production of interleukin-8 and monocyte chemoattractant protein-1 by certain canine MCT cell lines [150]. Oclacitinib appears to be able to reduce pruritus in dogs affected with cutaneous tumors (SoR B).

Urinary tract infections

Some authors observed urinary tract infection/cystitis [100,102] but bacteriuria is not an expected adverse effect in dogs with no prior history of urinary tract infection or predisposed condition. Oclacitinib can be used in dogs with occasional urinary tract infections (SoR B), but it is not recommended for dogs with recurrent episodes of bacterial cystitis (SoR C) [121].

2.5.2. In Atopic Dogs, during the Induction Period of ASIT

No studies have assessed the impact of oclacitinib during desensitization. Some dogs were receiving oclacitinib while being desensitized, but the consequences were not assessed (SoR C) [109]. Because of its mechanism of action, oclacitinib seems usable during the induction period of ASIT with no negative impacts (SoR C).

2.5.3. In Atopic Dogs, during Allergy Testing

No studies have assessed the impact of oclacitinib during allergy testing in atopic dogs. One pilot study used experimental models of canine AD and showed no influence of oclacitinib on allergen-specific IgE results. Oclacitinib can be used during allergy testing (SoR C).

2.5.4. In Atopic Dogs, during Dietary Trials

No negative effect on dietary trials has been published and oclacitinib can be used (SoR C).

2.5.5. In Pruritic Ectoparasitic Dermatoses

With the exception of demodicosis (confirmed or previous), in which case oclacitinib should be avoided (SoR C), a short course of treatment would be acceptable when initiating the treatment of a highly pruritic sarcoptic mange or flea infestation (SoR C).

2.5.6. With Vaccines

No data are available. In the summary of product characteristics, oclacitinib administration was associated with an adequate immune response to modified live vaccine canine distemper virus and canine parvovirus vaccination, but a decreased serological response to modified live vaccine canine parainfluenza and inactivated rabies vaccine. Oclacitinib can be used depending on the vaccine type (SoR C).

2.6. Lokivetmab

2.6.1. In Atopic Dogs, excluding the Induction Period of ASIT

During Flares (Reactive Therapy)

Lokivetmab subcutaneous injection results in an impressive improvement in pruritus between 4 and 24 h (SoR A) and is effective for the treatment of flares of canine AD (SoR A). Reductions in the pruritus score and in the lesional score were significant 28 days after one injection (SoR B). The lokivetmab dose used in Europe is a minimum of 1 mg/kg, and 2 mg/kg in North America.

In Non-Flare Periods (Proactive Therapy)

Lokivetmab is recommended for non-flare periods of canine AD (SoR A). The lesional score improved after the first injection and continued to improve after the second and the third injections (SoR C). Lokivetmab can delay disease flares in some atopic dogs (SoR C).

In Dogs with Superficial Pyoderma or Microbial Overgrowth

Lokivetmab can be recommended in dogs with canine AD and superficial pyoderma or microbial overgrowth (SoR C), even if, to date, no data are available to assess the efficacy of lokivetmab or the impact of lokivetmab on dogs with superficial pyoderma or microbial overgrowth. No data are available that suggest a pro-infectious role of lokivetmab when used in dogs suffering from allergic dermatitis (SoR C).

In Dogs with Specific Problems

Liver disorders

The strength of recommendation (SoR) was ranked as follows ^[6]: A—recommendation based on consistent and good-quality patient-oriented evidence; B—recommendation based on inconsistent or limited quality patient-oriented evidence; C—recommendation based on consensus, opinion, case studies, or disease-oriented evidence.

2.1. Systemic Glucocorticoids

2.1.1. In Atopic Dogs, excluding the Induction Period of ASIT

During Flares (Reactive Therapy)

In Non-Flare Periods (Proactive Therapy)

In Dogs with Superficial Pyoderma or Microbial Overgrowth

Few data are available. Daily oral administration of 0.75 mg/kg prednisolone for one month did not alter the skin microbiome of six asymptomatic atopic dogs ^[7]. Nevertheless, considering their potential pro-infectious characteristics, their use should be restricted in the case of secondary skin infections and infectious diseases (SoR C).

In Dogs with Specific Problems

Liver disorders Changes in liver parameters associated with the use of systemic glucocorticoids are commonly observed. In the case of long-term use, their detection by regular liver function tests is recommended. The use of glucocorticoids is not recommended in animals with liver failure (SoR C). Renal disorders The use of glucocorticoids is not recommended in dogs with renal disorders (SoR C). Diabetes mellitus Glucocorticoids stimulate gluconeogenesis. Lipogenesis is enhanced in certain areas of the body and adipose tissue may be redistributed away from the extremities to the trunk (SoR C). The use of glucocorticoids is associated with an increase in serum insulin but not serum fructosamine concentrations in dogs with canine AD (SoR B). Since prolonged use of systemic glucocorticoids can lead to the development of diabetes, their use in a diabetic animal, even if controlled, is not recommended (SoR C). Neoplastic diseases Long-term use can cause immunomodulation that can lead to the development of neoplasia (SoR C). The use of glucocorticoids is not generally recommended in dogs with cancers (SoR C) unless they are part of the chemotherapy regimen ^[8][9]. Urinary infections Routine urine cultures and assessment of bacteriuria by cystocentesis should be part of the monitoring for dogs on long-term glucocorticoids. Glucocorticoids should be used cautiously in dogs with occasional urinary tract infections and be avoided in dogs with recurrent urinary infections (more than two episodes in six months or more than three episodes per year) (SoR C) ^[10].

2.1.2. In Atopic Dogs, during the Induction Period of ASIT

Systemic glucocorticoids can be used during ASIT (SoR B) and can be used in the case of an adverse event during ASIT rush therapy (SoR B).

2.1.3. In Atopic Dogs, during Allergy Testing

2.1.4. In Atopic Dogs, during Dietary Trials

Systemic glucocorticoids can be used during the initial period of an elimination diet (SoR C).

2.1.5. In Pruritic Ectoparasitic Dermatoses

2.1.6. With Vaccines

2.2. Topical Glucocorticoids

2.2.1. In Atopic Dogs, excluding the Induction Phase of ASIT

During Flares (Reactive Therapy)

In Non-Flare Periods (Proactive Therapy)

Hydrocortisone aceponate can be recommended in non-flare periods (SoR A). The frequency of application can be reduced after one or two weeks of treatment, which reduces the risk of adverse reactions (SoR B). Twice weekly applications on previous lesional skin areas reduce relapses (SoR A). Skin thinning can be observed after 14 days of treatment (SoR B). The use of triamcinolone is also possible and effective, although there may be an increase in side effects (SoR B). With the use of other topical glucocorticoid formulations, there may be variations in efficacy and safety depending on the strength of the glucocorticoid, the chemical structure, and the vehicle ^[12][13]. Most topical corticosteroids are absorbed in quantities that can produce both systemic and local adverse effects ^[14]. These marked adverse effects may be observed with prolonged or frequent use and are more rapidly observed, more frequent, and more severe with potent topical corticoids (SoR C).

In Dogs with Superficial Pyoderma or Microbial Overgrowth

In Dogs with Specific Problems

No data are available, but hydrocortisone aceponate seems to be a safe molecule because of its particular metabolic pathway, i.e., in the skin with no systemic absorption (SoR C). Because of its potential local effect on skin (thinning), its use is not recommended in dogs suffering from other systemic diseases that have an impact on skin integrity (e.g., Cushing disease) (SoR C). Like with the use of other topical glucocorticoids, caution is required because systemic absorption, potencies and the risk of adverse reaction will vary with the glucocorticoid molecule (SoR C). Liver disorders No data are available but as hydrocortisone aceponate does not cause changes in biochemical parameters, this molecule could be used in dogs with liver disorders (SoR C). Caution is required with other topical glucocorticoids (SoR C). Renal disorders No data are available. Hydrocortisone aceponate does not cause changes in renal parameters so this molecule could be used in dogs with renal disorders, but regular biochemical tests are mandatory (SoR C). Diabetes mellitus No data are available. Due to its mode of action, hydrocortisone aceponate could be used in dogs with diabetes mellitus, but regular biochemical tests should be performed (SoR C). Like with other topical corticoids, there is a risk of developing diabetes mellitus as in humans with the cumulative dose and cumulative duration of use (SoR C) ^[15]. Neoplastic diseases No data are available. Hydrocortisone aceponate could be used in dogs with neoplastic diseases after evaluation of the benefit/risk ratio by the responsible veterinarian (SoR C). Urinary infections No data are available. Because of its mode of action, hydrocortisone aceponate could be used in dogs with urinary infection (SoR C).

2.2.2. In Atopic Dogs, during the Induction Phase of ASIT

No data are available, but topical glucocorticoids can be used during the induction period of ASIT (SoR C).

2.2.3. In Atopic Dogs, during Allergy Testing

Hydrocortisone aceponate and other topical glucocorticoids should be stopped at least two weeks prior to IDST as they can interfere with the cutaneous reactions (SoR B) ^[16][17]. No data are available but topical glucocorticoids should not interfere with specific allergen serology tests (SoR C).

2.2.4. In Atopic Dogs, during Dietary Trials

No data are available, but topical glucocorticoids can be used at the beginning of trials for localized lesions to relieve the animal (SoR C).

2.2.5. In Pruritic Ectoparasitic Dermatoses

2.2.6. With Vaccines

2.3. Antihistamines

2.3.1. In Atopic Dogs, Excluding the Induction Period of ASIT

During Flares (Reactive Therapy)

In Non-Flare Periods (Proactive Therapy)

In Dogs with Superficial Pyoderma or Microbial Overgrowth

Antihistamines can be used in dogs with superficial pyoderma or microbial overgrowth (SoR C).

In Dogs with Specific Problems

Liver disorders No data are available. First-generation antihistamines mainly have a hepatic metabolism. In humans, a dose reduction is recommended in the case of hepatic insufficiency, but their use is not contraindicated ^[18][19]. So, these molecules could be used in dogs with liver disorders, perhaps at a lower dose (SoR C). Renal disorders No data are available. Some antihistamines such as cetirizine have a renal metabolic route in humans, but the route is still not known in dogs ^[20]. In humans, in the case of renal insufficiency, a reduction in dose is recommended, but its use is not contraindicated ^[18][19]. Antihistamines could be used in dogs with renal disorders, perhaps at a lower dose (SoR C). Diabetes mellitus No data are available. Antihistamines appear to be usable in dogs with diabetes mellitus (SoR C). Neoplastic diseases No data are available. Antihistamines appear to be usable in dogs with neoplastic diseases (SoR C). Urinary infections No data are available. Antihistamines appear to be usable in dogs with urinary infections (SoR C).

2.3.2. In Atopic Dogs, during the Induction Period of ASIT

Antihistamines can be used during desensitization in dogs (SoR C).

2.3.3. In Atopic Dogs, during Allergologic Tests

2.3.4. In Atopic Dogs, during Dietary Trials

No data are available. Antihistamines are not contraindicated (SoR C) ^[21].

2.3.5. In Pruritic Ectoparasitic Dermatoses

Antihistamines can be used in cases of mild to moderate parasitic pruritus (SoR C).

2.3.6. During Vaccines

2.4. Ciclosporin A

2.4.1. In Atopic Dogs, excluding the Induction Period of ASIT

During Flares (Reactive Therapy)

In Non-Flare Periods (Proactive Therapy)

Ciclosporin is recommended to manage canine AD in non-flare periods (SoR A). It is possible to reduce the frequency of administration after two to four months depending on the clinical response, while maintaining the efficacy of the molecule with treatment on alternate days or twice a week (SoR A). A decrease in the daily dose is also possible (SoR B). At the beginning of treatment, the combination of ciclosporin (5 mg/kg/day) and prednisolone (1 mg/kg/day for 7 days, then eod for 14 days), accelerates the clinical response with no increase in severe adverse effects (SoR B), and with a threefold greater effect on pruritus in the first few days. The authors suggest modifying the protocol by rapidly reducing the prednisolone dose to 0.5 mg/kg/d (SoR C). EFA supplementation in the plateau stage (after two months) could improve pruritus and clinical signs (SoR B) and reduce the dose of ciclosporin (from 0.85 mg/kg/day). Gastrointestinal side effects, most often transient and moderate, are common (46% of cases) (SoR A) ^[22]. Neoformations are rare (SoR A). Papillomatous lesions are reported, usually not linked to the presence of papillomaviruses, but possibly in response to bacterial infections ^[23]. These lesions and gingival hyperplasia usually regress after stopping ciclosporin (SoR B). Infections were present in 11% of treated animals ^[24]. As the infections were mostly cutaneous (68%), it is difficult to confirm a role for the molecule given the naturally high frequency of infections during CAD and in the absence of studies with control groups ^[25]. Bacterial urinary tract infections (30% of infections mentioned) are neither statistically more frequent than in untreated dogs, nor are they accompanied by clinical urinary signs ^[26]. A link between clinical urinary bacterial infection and the use of the drug has therefore not been established, although caution is recommended and regular urinary analyses may be required during long-term treatment (SoR B).

In Dogs with Superficial Pyoderma or Microbial Overgrowth

In Dogs with Specific Problems

Liver disorders Ciclosporin, even when used at high doses and for long periods, does not appear to be hepatotoxic in dogs ^[24], but no data are available in the case of pre-existing liver disorders. The molecule does not seem to be advisable in animals with hepatic disorders because of its mainly hepatic metabolism via cytochrome P-450 ^[27]. However, ciclosporin seems to be beneficial to hepatocytes during porto-cavity shunting and improves hepatic biochemical parameters during chronic idiopathic hepatitis ^[28][29]. Ciclosporin is not recommended for liver disorders, but the benefit–risk balance should be assessed (SoR C). Renal disorders Unlike in humans, even when used at high doses and for long periods, ciclosporin does not appear to be nephrotoxic in dogs ^[24] and no adverse effects have been reported in studies on canine AD. No abnormalities in renal biochemical parameters were detected experimentally after two years of treatment in 38 dogs ^[30]. However, to the best of the authors’ knowledge, no studies have been conducted on animals with renal failure. Ciclosporin seems to be suitable for use in dogs with renal disorders, but the benefit–risk balance should be assessed and regular biochemical tests performed (SoR C). Diabetes mellitus Observations of diabetes mellitus in dogs monitored in studies are limited to one case of hyperglycemia and diabetes mellitus after three years of treatment with ciclosporin ^[31]. Clinical data suggest that treatment in West Highland white terriers is associated with increased incidence of diabetes mellitus ^[32]. Experimentally, ciclosporin may reversibly increase peripheral insulin resistance and decrease insulin secretion ^[33]. In a study of 16 dogs with canine AD, ciclosporin (5 mg/kg/day; six weeks) significantly increased glucose levels and decreased serum insulin concentrations, whereas fructosamine levels (statistically increased) remained within the normal range and no dog developed diabetes mellitus ^[34]. In diabetic dogs, the clearance of ciclosporin increased significantly and the half-life shortened compared with controls ^[25]. This led to the recommendation to avoid treating diabetic dogs with ciclosporin (SoR C). Neoplastic diseases No increase in the prevalence of neoplasia has been reported in published clinical studies. One study of 51 dogs given ciclosporin for six to 30 months did not show increased neoplasia compared with the general population ^[30], and ciclosporin treatment in canine AD was not a risk factor for cutaneous lymphoma ^[35]. No articles analyzed the effect of ciclosporin in animals with neoplastic diseases. However, the immune effects and the potential impact on tumor progression led to the recommendation to avoid using ciclosporin in dogs with neoplasia or when neoplasia is diagnosed during treatment (SoR C). Urinary tract infections Ciclosporin can be used in dogs with occasional urinary tract infections (SoR B) but is not recommended in dogs with recurrent episodes of bacterial cystitis (SoR C) ^[10].

2.4.2. In Atopic Dogs, during the Induction Period of ASIT

No data are available. An increase in the population of regulatory T cells could play a role in desensitization ^[36]. Ciclosporin administration increases populations of regulatory T cells in humans ^[37], and has no effect in dogs ^[38], but never reduces this population. Ciclosporin could react in synergy or have no effect on desensitization. Ciclosporin is usable during desensitization in dogs (SoR C).

2.4.3. In Atopic Dogs, during Allergologic Tests

One other study showed that ciclosporin reduced reactivity to the skin tests, but not the IgE assay, in relation to an Ascaris allergen ^[39], whereas two abstracts, one from an experimental study and the other from a clinical study, reported no effect ^[40][41]. Ciclosporin can be used without a therapeutic window before these sensitization tests are performed (SoR B).

2.4.4. In Atopic Dogs, during Dietary Trials

2.4.5. In Pruritic Ectoparasitic Dermatoses

External antiparasitics are rapidly effective, whereas ciclosporin is slow, so its use is not recommended (SoR C).

2.4.6. During Vaccines

2.5. Oclacitinib

2.5.1. In Atopic Dogs, excluding the Induction Period of Allergen-Specific Immunotherapy

During Flares (Reactive Therapy)

Due to the rapid and efficient reduction in pruritus, oclacitinib (SoR A) is effective for the treatment of flares, with efficacy obtained in a few hours (SoR B) or a few days (SoR A). The dose of oclacitinib is 0.4–0.6 mg/kg twice a day orally for 14 days, thereafter reduced to 0.4–0.6 mg/kg once a day (SoR A). When tapering oclacitinib therapy, a slight rebound of pruritus is observed (SoR B). When the molecule chosen for the control of canine AD is ciclosporin, oclacitinib can be used concomitantly at the beginning of the treatment to accelerate the reduction in pruritus (SoR B) during the flare. Hydrocortisone aceponate can also be combined with oclacitinib to prevent the relapse of pruritus and skin lesion when reducing the frequency of administration of oclacitinib from bid to sid (SoR A).

In Non-Flare Periods (Proactive Therapy)

Oclacitinib is safe and effective and is recommended for the long-term management of canine AD (SoR A). Adverse events associated with oclacitinib are uncommon (mainly gastro-intestinal) (SoR B).

In Dogs with Superficial Pyoderma or Microbial Overgrowth

In Dogs with Specific Problems

Liver disorders No data are available. In one case of necrolytic migratory erythema syndrome, oclacitinib was effective as long-term therapy (12 weeks) in controlling pruritus ^[43]. No study reported adverse hepatic effects in atopic dogs treated with oclacitinib. It thus seems that this molecule can be used in dogs with hepatic troubles, but the benefit–risk balance should be evaluated and a biochemical follow-up test conducted regularly (SoR C). Renal disorders No study reported adverse renal effects in atopic dogs treated with oclacitinib. It thus appears that this molecule can be used in dogs with renal troubles, but the benefit–risk balance should be evaluated and the biochemical profile checked regularly (SoR C). Diabetes mellitus No study reported signs of diabetes mellitus in atopic dogs treated with oclacitinib. It thus seems that this molecule can be used in dogs with diabetes mellitus, but the benefit–risk equation should be evaluated and the biochemical profile checked regularly (SoR C). Neoplastic diseases The summary of product characteristics prevents the use of this molecule in dogs with neoplastic diseases. The development of papilloma has also been reported in dogs. However, there is no association between the daily administration of oclacitinib and the odds of malignancies or benign skin masses ^[44]. Oclacitinib was a therapeutic option in one case of cutaneous epitheliotropic T-cell lymphoma ^[45]. Oclacitinib was well tolerated when administered in combination with carboplatin or doxorubicin in nine tumoral cases ^[46]. Oclacitinib was shown to modulate the production of interleukin-8 and monocyte chemoattractant protein-1 by certain canine MCT cell lines ^[47]. Oclacitinib appears to be able to reduce pruritus in dogs affected with cutaneous tumors (SoR B). Urinary tract infections Some authors observed urinary tract infection/cystitis ^[48][49] but bacteriuria is not an expected adverse effect in dogs with no prior history of urinary tract infection or predisposed condition. Oclacitinib can be used in dogs with occasional urinary tract infections (SoR B), but it is not recommended for dogs with recurrent episodes of bacterial cystitis (SoR C) ^[10].

2.5.2. In Atopic Dogs, during the Induction Period of ASIT

No studies have assessed the impact of oclacitinib during desensitization. Some dogs were receiving oclacitinib while being desensitized, but the consequences were not assessed (SoR C) ^[50]. Because of its mechanism of action, oclacitinib seems usable during the induction period of ASIT with no negative impacts (SoR C).

2.5.3. In Atopic Dogs, during Allergy Testing

2.5.4. In Atopic Dogs, during Dietary Trials

No negative effect on dietary trials has been published and oclacitinib can be used (SoR C).

2.5.5. In Pruritic Ectoparasitic Dermatoses

2.5.6. With Vaccines

2.6. Lokivetmab

2.6.1. In Atopic Dogs, excluding the Induction Period of ASIT

During Flares (Reactive Therapy)

In Non-Flare Periods (Proactive Therapy)

In Dogs with Superficial Pyoderma or Microbial Overgrowth

In Dogs with Specific Problems

Liver disorders No specific study has been performed, but lokivetmab does not cause changes in biochemical parameters (SoR C). Lokivetmab can thus be recommended in dogs with liver disorder (SoR C). Renal disorders No data are available. Renal parameters are not modified by lokivetmab (SoR C). Lokivetmab thus seems to be usable in dogs with renal disorder (SoR C). Diabetes mellitus No data are available. Lokivetmab does not stimulate gluconeogenesis (SoR C). Lokivetmab thus seems to be usable in dogs with diabetes mellitus (SoR C). Neoplastic diseases Few data are available. A monthly injection of lokivetmab at a dose of 2 mg/kg was effective in resolving and maintaining pruritus remission over a period of 15 months in a dog with widespread cutaneous mastocytosis ^[51] (SoR C). Similarly, it was used at a dose of 1.25 mg/kg in a dog with cutaneous epitheliotropic lymphoma in combination with prednisolone and resolved pruritus ^[52] (SoR C). Lokivetmab can be used in dogs with mastocytosis or epitheliotropic lymphoma and for other neoplastic diseases; however, although its use seems to be safe, there are no data on the safety of lokivetmab in the presence of tumor (SoR C). Urinary infections In clinical trials, lokivetmab does not induce urinary infections, or changes in biochemical, hematological, and renal parameters (SoR C). Lokivetmab can thus be recommended in dogs with urinary infections (SoR C).

2.6.2. In Atopic Dogs, during the Induction Period of ASIT

No negative effect on ASIT has been published and lokivetmab can be used during the induction period of ASIT (SoR C).

2.6.3. In Atopic Dogs, during Allergy Testing

No published data are available. Lokivetmab could be used during allergy tests without the need for the withdrawal of the drug before the tests are performed (SoR C).

2.6.4. In Atopic Dogs, during Dietary Trials

No negative effect on dietary trials has been reported and lokivetmab can be used (SoR C). However, due to its prolonged effect beyond six weeks in some dogs, the interpretation of the outcome of the eviction regime should be made with caution.

2.6.5. In Pruritic Ectoparasitic Dermatoses

No data are available. A single injection would be acceptable when initiating the treatment of a highly pruritic sarcoptic mange or FBH (SoR C).

2.6.6. With Vaccines

No data are available. The summary of product characteristics does not limit the use of lokivetmab during vaccination, except to recommend giving the injections at different time points. Lokivetmab can be used with vaccines (SoR C).