Dermatology: Practical and Conceptual Review | Dermatol Pract Concept. 2025;15(4):5749 1 Targeted Therapies and Pharmacologic Advances in Mucous Membrane Pemphigoid: A Comprehensive Review Vera Nikolaevna Busol1, Nikita Victorovich Kudryashov2 1 N.V. Sklifosovsky Institute of Clinical Medicine, Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia 2 Department of Pharmacology, Institute of Digital Biodesign and Modelling of Living Systems, Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia Key words: Autoimmune Bullous Dermatoses, Mucous Membrane Pemphigoid, Cicatricial Pemphigoid, Pemphigoid Antibodies, Novel therapies Citation: Busol VN, Kudryashov NV. Targeted Therapies and Pharmacologic Advances in Mucous Membrane Pemphigoid: A Comprehensive Review. Dermatol Pract Concept. 2025;15(4):5749. DOI: https://doi.org/10.5826/dpc.1504a5749 Accepted: July 20, 2025; Published: October 2025 Copyright: ©2025 Busol et al. This is an open-access article distributed under the terms of the Creative Commons Attribution- NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: None. Competing Interests: None. Authorship: All authors have contributed significantly to this publication. Corresponding Author: Vera Nikolaevna Busol, The Federal State Autonomous, Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of Russia, Sechenov University. 8-2 Trubetskaya str., Moscow, Russia, 119991. E-mail: verafbmusik@yandex.ru. Introduction: Mucous membrane pemphigoid (MMP) is a rare autoimmune bullous dermatosis which predominantly affects the mucous membranes and, occasionally, the skin. The exact pathogen- esis of MMP remains unclear and should be considered as a unique phenomenon, which involves the formation of subepithelial blisters and fibrosis. Objectives: This narrative review aimed to summarize the pharmacological agents which showed efficacy in the management of MMP but that are not included in the guidelines. Methods: We conducted a search on Google Scholar, PubMed, and the Web of Science databases con- cerning articles published in English on the management of MMP between January 2000 and February 2025; all the sourced articles were full-text reviewed. Results: We included 13 articles. The studied pharmacological agents are classified as immunosuppres- sive agents (leflunomide, sirolimus, daclizumab) and biologics (daclizumab, dupilumab, omalizumab, bevacizumab, aflibercept, cenegermin); the immunosuppressant leflunomide and the antimalarial agent hydroxychloroquine are also classified as disease-modifying antirheumatic drugs. Other pharmacologi- cal agents (colchicine, corticotropin, varenicline, lifitegrast) exert miscellaneous mechanisms. ABSTRACT 2 Review | Dermatol Pract Concept. 2025;15(4):5749 Introduction Mucous membrane pemphigoid (MMP) is a rare autoim- mune bullous dermatosis (AIBD) which predominantly af- fects mucous membranes and the skin. Generally, MMP has a late onset, and the mean age of patients ranges from 60 to 80 years; the association between the condition and HLA- DQB1*0301, HLA-DRB1*1101, HLA-DQA1*0505 alleles has been notes noted. The pathogenesis of MMP remains unclear and in- volves the formation of subepithelial blisters and fibrosis. The formation of blisters is linked to the production of an- tibodies (IgG and/or IgA) against the basement membrane proteins BP230 and BP180, α6 and β4 integrin subunits, laminin-332, laminin-6, type VII collagen. The activation of fibroblasts and hyperproduction of collagen may be associ- ated with the dysregulation of immunity, excessive release of pro- inflammatory molecules, and proteolytic enzymes [1]. Transforming growth factor beta (TGF-β) plays a major role in fibrosis, and an increased expression of TGF-β and alpha-smooth muscle actin were observed in conjunctiva samples taken from patients with MMP [2]. MMP develops through three distinct phases: injury, acute inflammation and proliferation, and fibrosis. Sub- epithelial tense blisters precede erosions and scarring. Histologically, the separation of the epithelium from the un- derlying connective tissue, leukocyte infiltrates, granulation tissue, and fibrosis may be seen. Direct immunofluorescence demonstrates peculiar linear depositions of immunoglobu- lins (IgG and/or IgA) and/or complement C3 along the basal membrane; indirect immunofluorescence (salt-split) and im- munoserological tests detect pathogenic autoantibodies [1]. Since 2002, several guidelines have evolved on the management of MMP. The First International Consensus on MMP [3] and the guidelines of the Brazilian Society of Dermatology [4] and the Japanese Dermatological Associa- tion [5] classify patients as low risk (oral and/or cutaneous lesions) or high risk (ocular, pharyngeal, laryngeal, esoph- ageal, and/or genital involvement), with adapted treatment options depending on the risk category; the guidelines of the French Society of Dermatology [6] are based on the loca- tion and disease severity. The European Guidelines (S3) [7] and the S2k guideline [8] offer lines of therapy, alternative combinations, and treatment options, depending on the clin- ical course, location, and response. Given the risk of disease progression and complications, early initiation of immuno- suppressive therapy is of vital importance; in severe cases, surgical treatment is considered. Nonetheless, there is no gold standard for treatment. This narrative review aimed to summarize the pharma- cological agents which showed efficacy in the management of MMP but that are not included in the earlier published guidelines. We conducted a search on Google Scholar, PubMed, and the Web of Science databases concerning articles pub- lished in English on the management of MMP between January 2000 and February 2025, using the search terms “mucous membrane pemphigoid”, “cicatricial pemphigoid”, “Brunsting-Perry pemphigoid”, “management”, “guide- lines”. All the sourced articles were full-text reviewed. The criteria for inclusion of the articles were publication in En- glish and the use of pharmacological options not included in the published guidelines. Drug Review We included 13 articles in English in which the diagnosis of MMP was verified and the data on the capacity to in- duce disease control and improvement and the absence of reported severe adverse effects of the suggested pharmaco- logical options were available (Table 1). The studied pharmacological agents are classified as immunosuppressive agents (leflunomide, sirolimus, dacli- zumab) and biologics (daclizumab, dupilumab, omalizumab, bevacizumab, aflibercept, cenegermin); the immunosuppres- sant leflunomide and the antimalarial agent hydroxychloro- quine are also classified as disease-modifying antirheumatic drugs. Other groups of pharmacological agents (colchicine, corticotropin, varenicline, lifitegrast) exert miscellaneous mechanisms, which are specified bellow. Interleukin (IL)-2 is a pro-inflammatory cytokine, also known as T cell growth factor; positive expression of IL-2 is observed in T cells, infiltrating the MMP-affected conjunc- tiva [9]. Daclizumab, a monoclonal anti-CD25 antibody, binds to the human IL-2 receptor (IL-2Rα) in the IL-2Rα Conclusion: Considering the severity of the condition, progressive fibrosis, and resistance to therapy, more research is required in relation to the pathogenesis of MMP and the efficacy and safety profile of novel pharmacological options. Pharmacological agents should provide the achievement and main- tenance of remission with minimal adverse effects. A broader spectrum of pharmacological agents will allow a personalized approach and more alternatives, in particular for recalcitrant cases, failure of the previous therapy, and in patients with MMP and malignancy. Review | Dermatol Pract Concept. 2025;15(4):5749 3 Table 1. Pharmacological Agents Reported in the Management of Mucous Membrane Pemphigoid. Drug Drug class Condition No. of reported patients No. of patients with improvement References Omalizumab Monoclonal anti-IgE antibody MMP 5 3 Alexandre et al. (2022) Daclizumab Monoclonal anti-CD25 antibody / IL-2R antagonist OcMMP 1 1 Papaliodis et al. (2003) Dupilumab IL-4/IL-13-inhibitor MMP BPP 1 1 1 1 Wang et al. (2024) Raef et al. (2021) Cenegermin rhNGF OcMMP 1 1 1 1 Abbot et al. (2024) Surico et al. (2024) Colchicine Anti-mitotic agent OrMMP MMP 6 12 5 8 Fribourg et al. (2024) Chaidemenos et al. (2011) Leflunomide Pyrimidine synthesis inhibitor OcMMP MMP 1 1 1 1 Smichowski et al. (2020) Boedeker et al. (2003) Hydroxychloroquine Antimalarial agent OcMMP BPP 1 1 1 1 Morel et al. (2022) Guerrero et al. (2025) Corticotropin Adrenocorticotropic hormone formulation OcMMP 15 9 Sharon et al. (2022) Varenicline Selective nAChR partial agonist OcMMP 4 1 Abbot et al. (2024) Lifitegrast ICAM-1 and LFA-1 antagonist OcMMP 10 2 Abbot et al. (2024) ectodomain, the binding site of IL-2 to immune cells, and inhibits B cell proliferation and IL-2-mediated T cell activa- tion. Papaliodis et al. (2003) reported one patient diagnosed with ocular MMP (OcMMP) and successfully treated with daclizumab [10]. An increased expression of IL-4 was noted in conjuncti- val sections of patients with OcMMP and in isolated fibro- blasts; IL-4 may exert a modulatory effect on macrophages via inducing m-CSF as well as uncontrolled extracellular matrix accumulation [11]. An elevated stromal expression of IL-13 is seen in active OcMMP, suggesting profibrotic and pro-inflammatory effects on human conjunctival fibro- blasts [12]. Dupilumab, a recombinant fully human IgG4 monoclonal antibody, suppresses inflammatory signaling via binding to the IL-4Rα subunit of IL-4 and IL-13 receptor complexes. Dupilumab combined with systemic corticoste- roids was reported as effective in a patient with multisite MMP (oral, genital, and cutaneous involvement) [13] and Brunsting-Perry pemphigoid [14]. The circulation of sera IgE autoantibodies against the BM components [15,16] as well as linear IgE depositions along BM on immunofluorescence [15,17] have been ob- served in patients with MMP. Omalizumab is a humanized monoclonal anti-IgE antibody which neutralizes total serum IgE via forming interactions with IgE Cɛ3 domains outside the FcɛRI-binding site and inhibiting FcɛRI and CD23 bind- ing. Omalizumab was reported to induce complete remission in three out of 5 patients with MMP (with oral, laryngeal, and genital MMP-related lesions) [18]. Neutrophils are present in inflammatory infiltrates at the acute stage and persist in MMP-affected tissues even when inflammation is visually resolved [9,19], and the in- volvement of other mechanisms (i.e., neutrophil recruitment) has been suggested in the pathogenesis of MMP [20]. Col- chicine, a bioactive plant alkaloid derived from Colchicum autumnale, is commonly used in gout flares, familial Medi- terranean fever, Behçet’s disease, psoriasis, Sweet’s syndrome, and erythema nodosum [21]. Colchicine inhibits neutrophil recruitment and disrupts the NLRP3 inflammasome assem- bly in neutrophils and monocytes through the inhibition of cellular P2X7 receptors; the suppression of β-tubulin polymerization and synthesis of microtubules is related to anti-mitotic properties [22]. Colchicine has been offered as a second-line option in oral MMP [23]; earlier colchicine was also suggested as a first-line corticosteroid-sparing agent in MMP [24]. Adverse effects (AEs) of colchicine include car- diomyopathy, cytopenia, elevation of hepatic transaminases, maculopapular rash, and alopecia [21]. 4 Review | Dermatol Pract Concept. 2025;15(4):5749 Vascular endothelial growth factor (VEGF) is involved in immune responses and proliferation, exerting signaling by binding to tyrosine kinase receptors, and bevacizumab and aflibercept neutralize VEGF via forming interactions with the receptor-binding regions. Subconjunctival and intravit- real injections of bevacizumab and aflibercept [39,40] have been reported in OcMMP; in the mentioned cases, these agents did not alter the severity of the disease course. How- ever, hypothetically, given their capacity to suppress angio- genesis and tissue remodeling, these agents may represent an opportunity to improve quality of life of patients with MMP as adjuvant therapy, although clinicians must be aware of drug-induced MMP [1]. Dry eye disease is frequently associated with OcMMP. Varenicline, a selective nicotinic acetylcholine receptor (nA- ChR) partial antagonist, induces the basal tear film formation by the lacrimal gland via the stimulation of the trigeminal parasympathetic nerve pathway [41]. Lifitegrast binds to the integrin lymphocyte function-associated antigen-1, prevent- ing its interaction with the intercellular adhesion molecule-1, blocking the formation of immunological synapse, T cell ac- tivation, and suppressing inflammatory cascades [42]. These agents are employed in dry eye disease; however, their effi- cacy was limited in OcMMP [35]. Mucous Membrane Pemphigoid and Malignancy In MMP, malignancy is reported in 15.5% of cases [43], while in patients with sera anti-laminin 332 antibodies (anti-laminin-332 MMP), the malignancy rate is 21–21.8% [43,44]. Laminin-332 is a structural glycoprotein of BM which is involved in extracellular matrix formation, cell proliferation and migration; its elevation has been observed in some tumors and may trigger autoimmune reactions and cross-reactivity with BM proteins [45,46]; thus, various stud- ies highlight an elevated malignancy risk in anti-laminin-332 MMP [44,47]. Another issue is MMP induced by malignancy treatment (e.g., radiation [48] and immune checkpoint in- hibitors [49]). The current guidelines do not contain sections on the man- agement of anti-laminin-332 MMP or of MMP in patients with a history of previous or concurrent malignancy, and the selection of therapy depends on lesion location and severity of the disease course. The use of immunosuppressive agents raises concerns over tumorigenesis risks [43,50,51], and sev- eral studies warn about elevated malignancy risks [52]. On the other hand, malignancy was detected before establish- ing the diagnosis of MMP in 47.1% of patients [43], and immunosuppressive agents have also been reported to have antineoplastic effects [51,53,54,55]. Corticosteroids remain among the most frequently indicated drugs in oncological conditions [56]. In paraneoplastic pemphigus, another au- toimmune blistering disease, the guidelines indicate systemic Hydroxychloroquine, an antimalarial and antirheumatic agent, exerts anti-inflammatory action via the disruption of antigen presentation in the background of intracellular pH alteration, processing of antigenic protein, and formation of the alpha and beta chains of major histocompatibility com- plex class II proteins, reducing T cell stimulation and immune responses [25]. Hydroxychloroquine has been reported to induce disease control in MMP [26] and Brunsting-Perry pemphigoid [27]; however, retinopathy, as well as car- diac and auditory toxicity [28] and dermatological AEs, in particular in autoimmune conditions [29], are linked to hydroxychloroquine. Leflunomide is an isoxazole derivative and pyrimidine synthesis inhibitor used in MMP. The drug inhibits the mi- tochondrial enzyme dihydroorotate dehydrogenase, disrupt- ing de novo synthesis of pyrimidine ribonucleotide uridine monophosphate, required for the progression from G1 to S phase in activated lymphocytes; these cytostatic and anti-proliferative effects may contribute to disease control in patients with MMP [30,31]. Diarrhea, elevation of liver enzymes, rash, and alopecia are the most frequent AEs of leflunomide in rheumatoid arthritis [32]. Melanocortins exert anti-inflammatory effects via the stimulation of glucocorticoid-dependent and glucocorticoid-independent pathways, reducing the release of pro-inflammatory cytokines and ROS. Repository cor- ticotropin injection (RCI) was earlier offered for systemic lupus erythematosus, given the reduction of B cell prolif- eration (possibly, via suppressing the activity of IL-6 and B-cell-activating factor of the tumor necrosis factor (TNF) family signaling) [33]. Furthermore, RCI has been sug- gested as a safe and well-tolerated alternative or adjunctive option for patients with severe and refractory OcMMP, in- ducing improvement in 60% of cases; no serious AE has been reported [34]. The recombinant human nerve growth factor (rhNGF) cenegermin improves corneal healing via binding to the tyro- sine kinase receptor TrkA and to p75NTR, promoting neu- ronal and epithelial cell growth. Abbot et al. (2024) reported the resolution of MMP-associated large, non-healing corneal defect in two patients treated with cenegermin [35,36], but Surico et al. (2024) highlighted patient monitoring due to the formation of corneal superficial plaque linked to posttreat- ment epithelial hyperplasia [36]. Sirolimus, a mammalian target of rapamycin (m-TOR) inhibitor, suppresses cytokine and growth factor receptor sig- naling and T cell progression from G1 to S [30]. Sirolimus was reported in combined and rotation therapy in OcMMP [37]. On the other hand, sirolimus-induced bullous pemphigoid was reported in two renal transplant recipients [38]; conse- quently, sirolimus should be employed with caution in auto- immune skin blistering diseases (AIBDs). Review | Dermatol Pract Concept. 2025;15(4):5749 5 potential of omalizumab; additionally, omalizumab can be em- ployed in desensitization to chemotherapeutic agents [75]. The rarity of MMP and its comorbidity with malignancy complicates the collection of further data on the association between MMP and malignant tumors and the impact of im- munosuppressive and other pharmacological agents on ma- lignancy risks. Future Perspectives Considering that the mechanisms of action of the above- mentioned agents are directed against the earlier discussed or hypothesized components of the pathogenesis of MMP and its complications, the studied drugs possess the potential for ad- ditional research concerning their efficacy and safety profile. The analysis of the guidelines shows the susceptibility to therapeutic novelties. Azathioprine, cyclophosphamide, and mitomycin C were included in the First International Con- sensus on MMP, while mycophenolate mofetil, rituximab, intravenous immunoglobulin, ciclosporin A, and etanercept were introduced by the guidelines of the French Society of Dermatology; a broader term “TNF-inhibitors” was later in- cluded in the S3 and S2k guidelines, Janus kinase inhibitors were indicated by the S2k guidelines for severe and recalci- trant cases. Corticosteroids are the most frequently employed immunosuppressive agents owning to their availability and efficiency. However, the unacceptance of long-term use of sys- temic corticosteroids due to severe AEs (e.g., aseptic hip ne- crosis, uncontrolled diabetes mellitus, and hypertension) was earlier highlighted in patients diagnosed with OcMMP [76], and there is a wide range of both topical and systemic ste- roid-sparing immunosuppressants, which are included in the guidelines and which exert effects through various pathways, reduce proliferation of immune cells, and release of patho- genic autoantibodies, with the underlying risk of compli- cations, therapy resistance, and recalcitrant disease course. The search for new options with minimal AEs continues, and time will show which pharmacological agents will be included in new guidelines; some options will remain out- side the list of recommended agents (e.g., thalidomide), while others may fade away. Furthermore, in preclinical studies, additional pharmaco- logical targets have been proposed. In a murine model of anti-laminin-332 MMP the inhi- bition of phosphodiesterase-4, responsible for cell signaling, resulted in the improvement of oral lesions [77]. Phosphatidylinositol-3-kinase-δ (PI3Kδ) is involved in cutaneous blistering following leukocyte activation after Fc gamma receptor-dependent binding to the skin-located im- mune complexes and subsequent production of proteases and ROS. Parsaclisib, a PI3Kδ-selective inhibitor, showed the amelioration of cutaneous lesions in the MMP-induced mouse model [78]. Additionally, laminin-332 is linked to corticosteroids and steroid-paring agents: cyclophosphamide, azathioprine, mycophenolate mofetil, rituximab, intravenous immunoglobulin (IVIG) [57,58]. The latter two were recently reported in anti-laminin-332 MMP [59,60,61], while cyclo- phosphamide is associated with bladder malignancy [62]. The use of mycophenolate mofetil raises concerns [52] but may also be associated with lower cancer risks [52,63]. Cu- riously, in inflammatory bowel disease, thiopurines (azathi- oprine) should be withdrawn in patients with active cancer, and the combination of thiopurines and TNF-alpha inhib- itors is linked to a higher lymphoma risk, which should be considered before the therapy selection [64]. The pharmacological agents discussed in this review may also be of interest in the management of MMP and malignancy. The antitumor effect of leflunomide has been confirmed in myeloma (NCT02509052) and will be examined in other clin- ical trials (NCT06540937, NCT04997993, NCT03709446, NCT04508790, NCT06229340, NCT06454383); the eval- uation of the effect of hydroxychloroquine in melanoma and various cancer types in different regimes is planned for clinical trials (NCT04464759, NCT05647330, NCT0632 8387, NCT07061717, NCT06949982, NCT05518110, NCT06229340, NCT06408298, NCT05733000, NCT0584 3188, NCT04841148). The expression of CD25 is observed in activated T cells and some malignancies; regulatory T lymphocytes (Tregs) constitute the tumor microenvironment, contributing to drug resistance via the suppression of immune surveillance [65]. Before its global withdrawal, daclizumab was reported in combination with chemotherapy and as an option to over- come the Tregs-mediated drug resistance [66,67]. Develop- ing pharmacological agents which target CD25 may be of use for the management of both malignancy and MMP. Given the link between the PI3K/mTOR signaling path- way and genetic mutations [51,68], sirolimus is a curi- ous option. Colchicine exerts anti-mitotic properties [69] and has been associated with a lower risk of colorectal cancer in immune-mediated inflammatory diseases [70]. Dupilumab is generally considered safe, but caution is re- quired in patients with cutaneous T-cell lymphoma [71,72]. However, the initially incorrect diagnosis of atopic derma- titis was suggested as an explanation for the poor progno- sis in such cases [52]. Patient monitoring is recommended for cenegermin, given its growth factor properties [73]. The anti-angiogenic agent bevacizumab is used in combination with immune and chemotherapy, but patient selection crite- ria should be developed due to the risk of hemorrhage and to high mortality rates [74]. The presence of IgE antibodies to BM proteins (e.g., laminin-332 [17]) were earlier reported in MMP, suggesting the 6 Review | Dermatol Pract Concept. 2025;15(4):5749 Intercellular adhesion molecule-1 (ICAM-1); Interleukin-2 receptor (IL-2R); IL-4 receptor alpha chain (IL-4Rα); Adre- nocorticotropic hormone (ACTH); Tropomyosin receptor kinase A (TrkA); Nerve growth factor receptor (p75NTR); Mucous membrane pemphigoid (MMP); Ocular mucous membrane pemphigoid (OcMMP); Oral mucous membrane pemphigoid (OrMMP); Brunsting-Perry pemphigoid (BPP). References 1. Rashid H, Lamberts A, Borradori L, et al. European guide- lines (S3) on diagnosis and management of mucous membrane pemphigoid, initiated by the European Academy of Derma- tology and Venereology – Part I. J Eur Acad Dermatol Vene- reol. 2021;35(9):1750-1764. DOI: 10.1111/jdv.17397. PMID: 34245180. 2. Di Zazzo A, Cutrupi F, De Antoniis MG, et al. Tissue Remodeling in Ocular Mucous Membrane Pemphigoid. Invest Ophthalmol Vis Sci. 2023;64(15):17. DOI: 10.1167/iovs.64.15.17. PMID: 38095906. 3. Chan LS, Ahmed AR, Anhalt GJ, et al. The first international con- sensus on mucous membrane pemphigoid: definition, diagnostic criteria, pathogenic factors, medical treatment, and prognostic indicators. Arch Dermatol. 2002;138(3):370-9. DOI: 10.1001 /archderm.138.3.370. PMID: 11902988. 4. Santi CG, Gripp AC, Roselino AM, et al. Consensus on the treatment of autoimmune bullous dermatoses: bullous pem- phigoid, mucous membrane pemphigoid and epidermolysis bullosa acquisita – Brazilian Society of Dermatology. An Bras Dermatol. 2019;94(2 Suppl 1):33-47. DOI: 10.1590/abd1806- 4841.2019940207. PMID: 31166405. 5. Ujiie H, Iwata H, Yamagami J, et al. Japanese guidelines for the management of pemphigoid (including epidermoly- sis bullosa acquisita). J Dermatol. 2019;46(12):1102-1135. DOI: 10.1111/1346-8138.15111. PMID: 31646663. 6. Bedane C, Prost C, Ingen-Housz-Oro S, Joly P, Bernard P; Cen- tres de référence des maladies bulleuses auto-immunes. Société Française de Dermatologie. Recommandations des centres de référence des maladies bulleuses auto-immunes pour le di- agnostic et la prise en charge de la pemphigoïde cicatricielle [Mucous membrane pemphigoid. Guidelines for the diagno- sis and treatment. Centres de référence des maladies bulleuses auto-immunes. Société Française de Dermatologie]. Ann Der- matol Venereol. 2011;138(3):259-63. French. DOI: 10.1016 /j.annder.2011.01.014. PMID: 21397156. 7. Schmidt E, Rashid H, Marzano AV, Lamberts A, Di Zenzo G, Diercks GFH, et al. European Guidelines (S3) on diagnosis and management of mucous membrane pemphigoid, initiated by the European Academy of Dermatology and Venereology – Part II. J Eur Acad Dermatol Venereol. 2021;35(10):1926-1948. DOI: 10.1111/jdv.17395. PMID: 34309078. 8. Hofmann SC, Günther C, Böckle BC, et al. S2k Guideline for the diagnosis and treatment of mucous membrane pemphigoid. J Dtsch Dermatol Ges. 2022;20(11):1530-1550. DOI: 10.1111 /ddg.14905. PMID: 36354061. 9. Elder MJ, Lightman S. The immunological features and patho- physiology of ocular cicatricial pemphigoid. Eye (Lond). 1994; 8(Pt 2):196-9. DOI: 10.1038/eye.1994.45. PMID: 7958021. malignancy development through the activation of PI3K and the Rho family of small GTPases [45,46], with decreased sig- naling of the latter after the administration of IVIG demon- strated by Murthy et al. (2024) [20]. Thus, the role of these pathways should be further clarified in MMP. MMP-associated fibrosis may be linked to the aldehyde dehydrogenase/retinoic acid (ALDH/RA)-mediated dendritic cell paracrine effect and activation of a pro-fibrotic pheno- type of fibroblasts. Patzelt et al. (2021) concluded that the ALDH inhibitor disulfiram does not reduce fibrosis in ocular and oral lesions in MMP-induced mice but improved cutane- ous lesions [79]. However, earlier disulfiram effectively alle- viated fibrotic changes in human OcMMP fibroblasts and in a mouse model [80]. In patients with MMP, high serum levels of IL-1 [81] and IL-5 [82] and an elevated expression of IL-6, IL-12, IL-17 [83], and IL-5 mRNA [84] in biopsy samples were reported. IL-1, IL-5, IL-6, IL-12, and IL-17 inhibitors are employed in dermatology; IL-5, IL-12/23, and IL-17 inhibitors were used in bullous pemphigoid [85,86]. Nonetheless, these agents oc- casionally paradoxically induce BP [87,88]. Moreover, com- plement inhibitors have been suggested for BP [85,86]; no report on the use of these agents in MMP was found. Summarizing the above-mentioned data, a broader spec- trum of pharmacological agents will allow a personalized approach and more alternatives, in particular for recalcitrant cases and failure of previous therapy. Moreover, given the participation of mechanisms other than the formation of au- toantibodies in the pathogenesis of MMP [20], it is advisable to collect more data on the impact of cytokines, complement, proteases, immune cells, and other agents in search of solu- tions to avoid severe complications and overcome therapy resistance. Conclusion We present the analysis of pharmacological agents used in the management of MMP but that are not included in earlier published guidelines. Considering the severity of the condi- tion, progressive fibrosis, and resistance to therapy, more re- search is required in relation to the pathogenesis of MMP and the efficacy and safety profile of novel pharmacological options. Pharmacological agents should provide the achieve- ment and maintenance of remission with minimal adverse effects. A broader spectrum of pharmacological agents will allow a personalized approach and more alternatives, in par- ticular for recalcitrant cases, failure of the previous therapy, and patients with MMP and malignancy. Abbreviations: Recombinant human nerve growth fac- tor (rhNGF); Nicotinic acetylcholine receptor (nAChR); Lymphocyte function-associated antigen-1 (LFA-1); Review | Dermatol Pract Concept. 2025;15(4):5749 7 Pemphigoid? Oral Dis. 2025;31(4):1237-1240. DOI: 10.1111 /odi.15193. PMID: 39497341. 24. Chaidemenos G, Sidiropoulos T, Katsioula P, Koussidou- Eremondi T. Colchicine in the management of mucous membrane pemphigoid. Dermatol Ther. 2011;24(4):443-5. DOI: 10.1111/j.1529-8019.2011.01438.x. PMID: 21910802. 25. Fox RI. Mechanism of action of hydroxychloroquine as an an- tirheumatic drug. Semin Arthritis Rheum. 1993;23(2):82-91. DOI: 10.1016/s0049-0172(10)80012-5. PMID: 8278823. 26. Morel M, DeGrazia T, Ward L, Behshad S, Kim HJ, Feldman R. Single Center Retrospective Study of Patients with Ocular Mu- cous Membrane Pemphigoid (MMP). Ocul Immunol Inflamm. 2022 ;30(1):256-261. DOI: 10.1080/09273948.2020.1783322. PMID: 32835566. 27. Guerrero JCS, Vincenzi K, Buñay PGP, et al. Brunsting-Perry Cicatricial Pemphigoid of the Scalp. IJCMCR. 2025;48(3):005. DOI: 10.46998/IJCMCR.2025.49.001210. 28. Misra DP, Gasparyan AY, Zimba O. Benefits and adverse effects of hydroxychloroquine, methotrexate and colchicine: searching for repurposable drug candidates. Rheumatol Int. 2020;40(11):1741- 1751. DOI: 10.1007/s00296-020-04694-2. PMID: 32880032. 29. Sharma AN, Mesinkovska NA, Paravar T. Characterizing the adverse dermatologic effects of hydroxychloroquine: A sys- tematic review. J Am Acad Dermatol. 2020;83(2):563-578. DOI: 10.1016/j.jaad.2020.04.024. PMID: 32289395. 30. Smichowski AM, Caputo VD, Romeo C, Rivero E, Morales NS, Casado G. Ocular cicatricial pemphigoid: Methotrexate as an initial treatment? Reumatol Clin (Engl Ed). 2022;18(1):30-32. DOI: 10.1016/j.reumae.2020.10.003. PMID: 34088654. 31. Boedeker CC, Termeer CC, Staats R, Ridder GJ. Cicatricial pem- phigoid in the upper aerodigestive tract: diagnosis and manage- ment in severe laryngeal stenosis. Ann Otol Rhinol Laryngol. 2003;112(3):271-5. DOI: 10.1177/000348940311200314. PMID: 12656421. 32. Kaltwasser JP, Behrens F. Leflunomide: long-term clinical ex- perience and new uses. Expert Opin Pharmacother. 2005;6(5): 787-801. DOI: 10.1517/14656566.6.5.787. PMID: 15934905. 33. Askanase AD, Furie RA. A Narrative Review of Repository Cor- ticotropin Injection for the Treatment of Systemic Lupus Ery- thematosus. Adv Ther. 2022;39(7):3088-3103. DOI: 10.1007 /s12325-022-02160-y. PMID: 35641860. 34. Sharon Y, Anesi SD, Martinez CE, Huang AJW, Foster CS, Chu DS. Repository Corticotropin Injection as an Alternative Treatment for Refractory Ocular Mucous Membrane Pemphigoid. Cornea. 2022;41(1):45-51. DOI: 10.1097/ICO.000000000000277. PMID: 34050065. 35. Abbott KS, Palestine AG, Hauswirth SG, Gregory DG, Patnaik JL, Reddy AK. Treatment of Ocular Surface Disease in Ocular Cicatricial Pemphigoid. Ocul Immunol Inflamm. 2024; 32(10):2479-2485. DOI: 10.1080/09273948.2024.2413892. PMID: 39383489. 36. Surico PL, Kaufman AR, Lin J, Dehghani S, Dana R. Corneal Superficial Plaque Formation After Recombinant Human Nerve Growth Factor Use in a Patient With Neurotrophic Keratopa- thy and Limbal Stem Cell Deficiency From Mucous Membrane Pemphigoid. Cornea. 2024;43(7):899-902. DOI: 10.1097/ ICO.0000000000003442. PMID: 38015976. 37. Morelon E, Mamzer-Bruneel MF, Peraldi MN, Kreis H. Sirolimus: a new promising immunosuppressive drug. Towards a rationale for its use in renal transplantation. Nephrol Dial Transplant. 2001;16(1):18-20. Doi: 10.1093/ndt/16.1.18. PMID: 11208987. 10. Papaliodis GN, Chu D, Foster CS. Treatment of ocular inflam- matory disorders with daclizumab. Ophthalmology. 2003; 110(4):786-9. DOI: 10.1016/S0161-6420(02)01932-2. PMID: 12689903. 11. Razzaque MS, Ahmed BS, Foster CS, Ahmed AR. Effects of IL-4 on conjunctival fibroblasts: possible role in ocular cicatricial pemphigoid. Invest Ophthalmol Vis Sci. 2003;44(8):3417-23. DOI: 10.1167/iovs.02-1084. PMID: 12882790. 12. Saw VP, Offiah I, Dart RJ, et al. Conjunctival interleukin-13 expression in mucous membrane pemphigoid and functional effects of interleukin-13 on conjunctival fibroblasts in vitro. Am J Pathol. 2009;175(6):2406-15. DOI: 10.2353/ajpath.2009 .090579. PMID: 19910508. 13. Wang Z, Liu X, Ni J, Qi Y, Song Z, Piao Y. Successful Treatment of Mucous Membrane Pemphigoid with Dupilumab: A Case Re- port. Acta Derm Venereol. 2024;104:adv40162. DOI: 10.2340 /actadv.v104.40162. PMID: 39188088. 14. Raef HS, Elmariah SB. Successful Treatment of Brunsting-Perry Cicatricial Pemphigoid With Dupilumab. J Drugs Dermatol. 2021;20(10):1113-1115. DOI: 10.36849/JDD.6032. PMID: 34636516. 15. Corti L, Fanoni D, Venegoni L, Muratori S, Recalcati S, Berti E. Detection of IgE autoantibodies in mucous membrane pem- phigoid and their association with disease severity. G Ital Der- matol Venereol. 2020;155(6):754-759. DOI: 10.23736/S0392 -0488.18.06167-9. PMID: 30298707. 16. Yayli S, Pelivani N, Beltraminelli H, et al. Detection of lin- ear IgE deposits in bullous pemphigoid and mucous mem- brane pemphigoid: a useful clue for diagnosis. Br J Dermatol. 2011;165(5):1133-7. DOI: 10.1111/j.1365-2133.2011.10481.x. PMID: 21711326. 17. Natsuga K, Nishie W, Shinkuma S, et al. Circulating IgA and IgE autoantibodies in antilaminin-332 mucous membrane pemphi- goid. Br J Dermatol. 2010;162(3):513-7. DOI: 10.1111/j.1365 -2133.2009.09508.x. PMID: 19751242. 18. Alexandre M, Bohelay G, Gille T, et al. Rapid Disease Control in First-Line Therapy-Resistant Mucous Membrane Pemphigoid and Bullous Pemphigoid with Omalizumab as Add-On Therapy: A Case Series Of 13 Patients. Front Immunol. 2022;13:874108. DOI: 10.3389/fimmu.2022.874108. PMID: 35514989. 19. Williams GP, Nightingale P, Southworth S, et al. Conjuncti- val Neutrophils Predict Progressive Scarring in Ocular Mu- cous Membrane Pemphigoid. Invest Ophthalmol Vis Sci. 2016;57(13):5457-5469. DOI: 10.1167/iovs.16-19247. PMID: 27760272. 20. Murthy S, Patzelt S, Künstner A, Busch H, Schmidt E, Sadik CD. Intravenous Ig Ameliorates Disease in a Murine Model of Anti-Laminin 332 Mucous Membrane Pemphigoid. J Invest Dermatol. 2024;144(12):2671-2681.e1. DOI: 10.1016/j.jid .2024.02.038. PMID: 38692406. 21. Sardana K, Sinha S, Sachdeva S. Colchicine in Dermatology: Rediscovering an Old Drug with Novel Uses. Indian Dermatol Online J. 2020 Sep 19;11(5):693-700. DOI: 10.4103/idoj.IDOJ _475_20. PMID: 33235833. 22. Robertson S, Martínez GJ, Payet CA, et al. Colchicine therapy in acute coronary syndrome patients acts on caspase-1 to suppress NLRP3 inflammasome monocyte activation. Clin Sci (Lond). 2016;130(14):1237-46. DOI: 10.1042/CS20160090. PMID: 27129183. 23. Fribourg E, Chuy V, Fenelon M, Catros S, Fricain JC. Is There a Role for Colchicine in the Treatment of Oral Mucous Membrane 8 Review | Dermatol Pract Concept. 2025;15(4):5749 53. Fojnica A, Gromilic Z, Ali Mohamed YA, Akhtar S, Vranic S. The potential role of cyclosporine A in cancer treatment: a compre- hensive literature review. Contemp Oncol (Pozn). 2024;28(4): 271-282. DOI: 10.5114/wo.2024.147009. PMID: 39935757. 54. Benjanuwattra J, Chaiyawat P, Pruksakorn D, Koonrungse- somboon N. Therapeutic potential and molecular mechanisms of mycophenolic acid as an anticancer agent. Eur J Pharmacol. 2020;887:173580. DOI: 10.1016/j.ejphar.2020.173580. PMID: 32949604. 55. Nam HJ, Kim YE, Moon BS, et al. Azathioprine antagonizes aberrantly elevated lipid metabolism and induces apoptosis in glioblastoma. iScience. 2021;24(3):102238. DOI: 10.1016/j.isci .2021.102238. PMID: 33748720. 56. Goodman RS, Johnson DB, Balko JM. Corticosteroids and Can- cer Immunotherapy. Clin Cancer Res. 2023;29(14):2580-2587. DOI: 10.1158/1078-0432.CCR-22-3181. PMID: 36648402. 57. Huang S, Anderson HJ, Lee JB. Paraneoplastic pemphigus / paraneoplastic autoimmune multiorgan syndrome: Part II. Diag- nosis and management. J Am Acad Dermatol. 2024;91(1):13-22. DOI: 10.1016/j.jaad.2023.08.084. PMID: 37714216. 58. Antiga E, Bech R, Maglie R, et al. S2k guidelines on the manage- ment of paraneoplastic pemphigus/paraneoplastic autoimmune multiorgan syndrome initiated by the European Academy of Der- matology and Venereology (EADV). J Eur Acad Dermatol Vene- reol. 2023;37(11):2378-2379. DOI: 10.1111/jdv.19489. PMID: 36965110. 59. Tarnowietzki E, Peters T, Kraus L, Schmidt E, Scharffetter- Kochanek K. Remission of Anti-laminin 332 Mucous Mem- brane Pemphigoid Associated with Non-small Cell Lung Cancer after Therapy with Rituximab and Intravenous Immu- noglobulin. Acta Derm Venereol. 2020;100(17):adv00301. DOI: 10.2340/00015555-3621. PMID: 32852563. 60. Gitin A, Porta AD, Bisbee E, Braunlich K, Motaparthi K. Anti-laminin 332 mucous membrane pemphigoid in a young woman treated with rituximab. Dermatol Online J. 2022;28(4). DOI: 10.5070/D328458517. PMID: 36259856. 61. Hügel R, Lang A, Lhotta K, et al. Anti-laminin 332 mucous membrane pemphigoid with laryngeal involvement – adjuvant treatment with immunoadsorption and rituximab. J Dtsch Der- matol Ges. 2018;16(7):897-900. DOI: 10.1111/ddg.13569. PMID: 29927519. 62. Chou WH, McGregor B, Schmidt A, et al. Cyclophosphamide- associated bladder cancers and considerations for survivorship care: A systematic review. Urol Oncol. 2021;39(10):678-685. DOI: 10.1016/j.urolonc.2021.05.017. PMID: 34134927. 63. Hirunsatitpron P, Hanprasertpong N, Noppakun K, Pruksakorn D, Teekachunhatean S, Koonrungsesomboon N. Mycophenolic acid and cancer risk in solid organ transplant recipients: Systematic review and meta-analysis. Br J Clin Phar- macol. 2022;88(2):476-489. DOI: 10.1111/bcp.14979. PMID: 34240462. 64. Gordon H, Biancone L, Fiorino G, et al. ECCO Guidelines on Inflammatory Bowel Disease and Malignancies. J Crohns Colitis. 2023;17(6):827-854. DOU: 10.1093/ecco-jcc/jjac187. PMID: 36528797. 65. Peng Y, Tao Y, Zhang Y, Wang J, Yang J, Wang Y. CD25: A po- tential tumor therapeutic target. Int J Cancer. 2023;152(7): 1290-1303. DOI: 10.1002/ijc.34281. PMID: 36082452. 66. Ceesay MM, Matutes E, Taylor GP, et al. Phase II study on com- bination therapy with CHOP-Zenapax for HTLV-I associated 38. Atzori L, Conti B, Zucca M, Pau M. Bullous pemphigoid in- duced by m-TOR inhibitors in renal transplant recipients. J Eur Acad Dermatol Venereol. 2015;29(8):1626-30. DOI: 10.1111 /jdv.12662. PMID: 25174440. 39. Hwang S, Kuo SC. Corneal perforation in ocular cicatricial pem- phigoid: A CARE-compliant case report. Medicine (Baltimore). 2021;100(51):e28266. DOI: 10.1097/MD.0000000000028266. PMID: 34941105. 40. Stan C, Diaconu E, Hopirca L, Petra N, Rednic A, Stan C. Oc- ular cicatricial pemphigoid. Rom J Ophthalmol. 2020;64(2): 226-230. PMID: 32685792. 41. Wirta D, Lipsky W, Toyos M, et al. Recombinant human nerve growth factor (cenegermin) for moderate-to-severe dry eye: phase II, randomized, vehicle-controlled, dose-ranging trial. BMC Ophthalmol. 2024;24(1):290. DOI: 10.1186/s12886-024- 03564-w. PMID: 39020305. 42. Zhong M, Gadek TR, Bui M, et al. Discovery and Development of Potent LFA-1/ICAM-1 Antagonist SAR 1118 as an Oph- thalmic Solution for Treating Dry Eye. ACS Med Chem Lett. 2012;3(3):203-6. DOI: 10.1021/ml2002482. PMID: 24900456. 43. Kianfar N, Dasdar S, Camilleri MJ, Lehman JS. Mucous mem- brane pemphigoid and malignancy: Systematic review and meta-analysis of 1429 patients. JAAD Reviews. 2024;1:82-92. DOI:10.1016/j.jdrv.2024.07.003 44. Shi L, Li X, Qian H. Anti-Laminin 332-Type Mucous Membrane Pemphigoid. Biomolecules. 2022;12(10):1461. DOI: 10.3390 /biom12101461. PMID: 36291670. 45. Nonnast E, Mira E, Mañes S. The role of laminins in cancer patho- biology: a comprehensive review. J Transl Med. 2025;23(1):83. DOI: 10.1186/s12967-025-06079-0. PMID: 39825429. 46. Patzelt S, Schmidt E. Autoimmunity against laminin 332. Front Im- munol. 2023;14:1250115. DOI: 10.3389/fimmu.2023.1250115. PMID: 37638011. 47. Li X, Pas HH, Qian H, et al. Potential correlation between anti-laminin 332 autoantibodies and malignant tumours in anti-BP180-type mucous membrane pemphigoid. Clin Exp Dermatol. 2024;49(9):1075-1076. DOI: 10.1093/ced/llae124. PMID: 38634807. 48. Syal A, Lott DG, Karle WE. Radiation-Induced Laryngeal Mucous Membrane Pemphigoid. Ann Otol Rhinol Laryngol. 2023;132(10):1261-1264. DOI: 10.1177/00034894221139121. PMID: 36433793. 49. Kotnik N, Diercks GFH, Jalving H, et al. Pemphigoid diseases as immune-related adverse effect following immune checkpoint inhibitors: A clinical case series of a diverse spectrum. JAAD Case Rep. 2025;61:100-106. DOI: 10.1016/j.jdcr.2025.03.021. PMID: 40538786. 50. Nouri A, Olbrich H, Schmidt E, Ludwig RJ, Curman P. Increased risk of skin cancers in mucous membrane pemphigoid: a large-scale matched cohort study of 117 million US individu- als. Front Med (Lausanne). 2025;12:1585167. DOI: 10.3389 /fmed.2025.1585167. PMID: 40248080. 51. Eckembrecher DG, Eckembrecher FJ, Camacho I, et al. A re- view of heart transplant immunosuppressants and nonmela- noma skin cancer. Arch Dermatol Res. 2023;315(9):2491-2503. DOI: 10.1007/s00403-023-02646-x. PMID: 37256379. 52. Gu SL, Nath S, Markova A. Safety of Immunomodulatory Systemic Therapies Used in the Management of Immune-Related Cutane- ous Adverse Events. Pharmaceuticals (Basel). 2023;16(11):1610. DOI: 10.3390/ph16111610. PMID: 38004475. Review | Dermatol Pract Concept. 2025;15(4):5749 9 78. Ghorbanalipoor S, Emtenani S, Parker M, et al. Cutaneous kinase activity correlates with treatment outcomes following PI3K delta inhibition in mice with experimental pemphigoid diseases. Front Immunol. 2022;13:865241. DOI: 10.3389/fimmu.2022.865241. PMID: 36248903. 79. Patzelt S, Pigors M, Steenbock H, et al. Increased Fibrosis in a Mouse Model of Anti-Laminin 332 Mucous Membrane Pem- phigoid Remains Unaltered by Inhibition of Aldehyde Dehy- drogenase. Front Immunol. 2022;12:812627. DOI: 10.3389 /fimmu.2021.812627. PMID: 35197965. 80. Ahadome SD, Abraham DJ, Rayapureddi S, et al. Aldehyde dehydrogenase inhibition blocks mucosal fibrosis in human and mouse ocular scarring. JCI Insight. 2016;1(12):e87001. DOI: 10.1172/jci.insight.87001. PMID: 27699226. 81. Kumari S, Bhol KC, Rehman F, Foster CS, Ahmed AR. Inter- leukin 1 components in cicatricial pemphigoid. Role in intrave- nous immunoglobulin therapy. Cytokine. 2001;14(4):218-24. DOI: 10.1006/cyto.2001.0877. PMID: 11448121. 82. Letko E, Bhol K, Colon J, Foster CS, Ahmed AR. Biology of interleukin-5 in ocular cicatricial pemphigoid. Graefes Arch Clin Exp Ophthalmol. 2002;240(7):565-9. DOI: 10.1007/s00417 -002-0497-4. PMID: 12136288. 83. Suelves AM, Zhao TZ, Siddique SS, Foster CS. Profile of local interleukin expression in a cohort of ocular cicatricial pemphi- goid patients. Invest Ophthalmol Vis Sci. 2012;53(13):8112-7. DOI: 10.1167/iovs.11-9322. PMID: 23081979. 84. Caproni M, Calzolari A, Giomi B, Santucci M, Ficarra G, Fabbri P. IL-4, IL-5, TGF-beta1 and IFN-gamma mRNAs detected by a new in situ amplification system in cicatricial pemphigoid. Exp Dermatol. 2002;11(5):421-7. DOI: 10.1034/j.1600-0625 .2002.110505.x. PMID: 12366695. 85. Karakioulaki M, Eyerich K, Patsatsi A. Advancements in Bullous Pemphigoid Treatment: A Comprehensive Pipeline Update. Am J Clin Dermatol. 2024;25(2):195-212. DOI: 10.1007/s40257- 023-00832-1. PMID: 38157140. 86. Khalid SN, Khan ZA, Ali MH, Almas T, Khedro T, Raj Nagarajan V. A blistering new era for bullous pemphigoid: A scop- ing review of current therapies, ongoing clinical trials, and future directions. Ann Med Surg (Lond). 2021;70:102799. DOI: 10.1016 /j.amsu.2021.102799. PMID: 34540212. 87. Zhang J, Wang SH, Zuo YG. Paradoxical phenomena of bullous pemphigoid induced and treated by identical biologics. Front Im- munol. 2023;13:1050373. DOI: 10.3389/fimmu.2022.1050373. PMID: 36685489. 88. Tanaka A, Fujimura Y, Fuke S, Izumi K, Ujiie H. A case of bul- lous pemphigoid developing under treatment with benralizumab for bronchial asthma. J Dermatol. 2023;50(9):1199-1202. DOI: 10.1111/1346-8138.16811. PMID: 37122191. adult T-cell leukaemia/lymphoma (ATLL). Leuk Res. 2012;36(7): 857-61. DOI: 10.1016/j.leukres.2011.12.004. PMID: 22209076. 67. Iglesias-Escudero M, Arias-González N, Martínez-Cáceres E. Regulatory cells and the effect of cancer immunotherapy. Mol Cancer. 2023;22(1). DOI: 10.1186/s12943-023-01714-0. PMID: 36739406. 68. Ali ES, Mitra K, Akter S, et al. Recent advances and limitations of mTOR inhibitors in the treatment of cancer. Cancer Cell Int. 2022;22(1):284. DOI: 10.1186/s12935-022-02706-8.  PMID: 36109789. 69. Rubicondo M, Ciardelli G, Mattu C, Tuszynski JA. Recent ad- vancements in colchicine derivatives: Exploring synthesis, activ- ities, and nanoformulations for enhanced therapeutic efficacy. Drug Discovery Today. 2025;30(3):104312. DOI: 10.1016 /j.drudis.2025.104312. PMID: 39947582. 70. Yeh JJ, Liw PX, Wong YS, et al. The effect of colchicine on cancer risk in patients with immune-mediated inflammatory diseases: a time-dependent study based on the Taiwan’s National Health Insurance Research Database. Eur J Med Res. 2024;29(1):245. DOI: 10.1186/s40001-024-01836-1. PMID: 38649928. 71. Guo S, Wang L, Bu D, Liu F. Tumors in the setting of dup- ilumab use: A review of the literature. World Allergy Organ J. 2024;18(1):101006. DOI: 10.1016/j.waojou.2024.101006. PMID: 39758935. 72. Ferreira C, Freitas E, Torres T. Efficacy and safety of dupi- lumab in a patient with metastatic clear cell renal cell car- cinoma. J Int Med Res. 2024;52(11):3000605241297551. DOI: 10.1177/03000605241297551. PMID: 39575618. 73. Deeks ED, Lamb YN. Cenegermin: A Review in Neurotrophic Keratitis. Drugs. 2020;80(5):489-494. DOI: 10.1007/s40265- 020-01289-w. PMID: 32185680. 74. Hayes DF. Bevacizumab treatment for solid tumors: boon or bust? JAMA. 2011;305(5):506-8. DOI: 10.1001/jama.2011.57. PMID: 21285431. 75. Vultaggio A, Petrella MC, Tomao F, et al. The anti-IgE monoclonal antibody omalizumab as adjuvant treatment in desensitization to carboplatin in patients with ovarian cancer. Gynecol Oncol Rep. 2021;38:100880. DOI: 10.1016/j.gore.2021.100880. PMID: 34926761. 76. Neumann R, Tauber J, Foster CS. Remission and recurrence after withdrawal of therapy for ocular cicatricial pemphigoid. Ophthalmology. 1991;98(6):858-62. DOI: 10.1016/s0161- 6420(91)32209-7. PMID: 1866137. 77. Tofern S, Fähnrich A, Künzel S, et al. 075 Inhibition of phosphodiesterase-4 significantly decreases oral mucosa lesions in experimental anti-laminin 332 mucous membrane pemphi- goid. Journal of Investigative Dermatology. 2019;139(9):S227. DOI: 10.1016/j.jid.2019.07.078