Gut instinct: Using tofacitinib to treat alopecia areata in the context of comorbid inflammatory bowel disease

Abstract

Alopecia areata (AA) is an autoimmune form of hair loss characterized by T-cell-mediated damage to hair follicles.1Xing L. Dai Z. Jabbari A. et al.Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition.Nat Med. 2014; 20: 1043-1049Crossref PubMed Scopus (454) Google Scholar Inflammatory bowel disease (IBD) is an autoimmune disease of the bowel characterized by dysregulation of T cells, increased production of proinflammatory cytokines (eg, interleukin [IL] 6, IL-23, IL-12, and IL-21), and intestinal epithelial dysfunction.2Salas A. Hernandez-Rocha C. Duijvestein M. et al.JAK–STAT pathway targeting for the treatment of inflammatory bowel disease.Nat Rev Gastroenterol Hepatol. 2020; 17: 323-337Crossref PubMed Scopus (96) Google Scholar Genome-wide association studies, performed separately in AA and IBD populations, reveal overlapping susceptibility loci in AA and Crohn disease (PRDX5 and IL-2RA) and AA and ulcerative colitis (UC) (IL-2/IL-21).3Festen E.A.M. Goyette P. Scott R. et al.Genetic variants in the region harbouring IL2/IL21 associated with ulcerative colitis.Gut. 2009; 58: 799-804Crossref PubMed Scopus (118) Google Scholar,4Petukhova L. Duvic M. Hordinsky M. et al.Genome-wide association study in alopecia areata implicates both innate and adaptive immunity.Nature. 2010; 466: 113-117Crossref PubMed Scopus (479) Google Scholar The incidence of comorbid AA and IBD is unknown. Despite the success of biologics for the treatment of IBD, it may be that some biologics, in particular tumor necrosis factor α inhibitors, precipitate AA. The Janus kinase (JAK) inhibitor tofacitinib is approved for the treatment of UC, and there are several ongoing trials of other JAK inhibitors for IBD. JAK inhibitors are an emerging treatment for AA.1Xing L. Dai Z. Jabbari A. et al.Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition.Nat Med. 2014; 20: 1043-1049Crossref PubMed Scopus (454) Google Scholar,5Liu L.Y. Craiglow B.G. Dai F. King B.A. Tofacitinib for the treatment of severe alopecia areata and variants: a study of 90 patients.J Am Acad Dermatol. 2017; 76: 22-28Abstract Full Text Full Text PDF PubMed Scopus (159) Google Scholar In this study, we describe the results of treatment of patients with comorbid IBD and AA with tofacitinib. We conducted a retrospective chart review of patients aged ≥18 years seen in the clinic of B.A.K. between July 2014 and August 2019 who had a diagnosis of both AA and either UC or Crohn disease and who underwent treatment with tofacitinib. The patients had been referred for AA. Physician notes documenting patient encounters were reviewed. After discussing treatment options with the patients and their gastroenterologists, tofacitinib was started. Information regarding age, gender, disease course, and therapies was obtained. The patients' IBD status (ie, controlled or not) during treatment with tofacitinib was determined by the gastroenterologist. A total of 9 patients with both AA and IBD underwent treatment with tofacitinib (Table I). The average age of onset of AA was 21.8 years (standard deviation, 13.2). The median severity of alopecia tool score was 100 (range, 45-100). Eight patients had a diagnosis of UC, and 1 had a diagnosis of Crohn disease. The onset of AA relative to that of IBD and vice versa was mixed (IBD developed prior to AA in 55.6% of the patients, AA developed first in 33.3%, and the order of the onset was unknown in 11.1%). Six of 7 patients with active IBD (85.7%) achieved remission of both IBD and AA with tofacitinib; 3 of these patients received concomitant therapy for their IBD, and 2 received concomitant therapy for their AA (Table I). One patient (patient 5) did not experience control of either her UC or AA with tofacitinib.Table ICharacteristics and outcomes of patients with comorbid AA and IBD treated with tofacitinibPatientDxSexAge (years) (at the time of chart review)Onset of AA relative to IBDIBD control with tofacitinib (Y/N)Dose of tofacitinib, duration of tofacitinib treatmentConcomitant IBD therapiesSALT scores (prior to tofacitinib/during tofacitinib)Other comorbidities1UCF21AA then UCYTofacitinib 10 mg BID, 34 monthsNone100/02Crohn diseaseF36Crohn disease then AAYInvestigational JAK inhibitor (for 6 months) followed by tofacitinib 5 mg BID, 10 monthsNone100/03UCF22AA then UCYTofacitinib 5 mg BID, 30 monthsMesalamine45/04UCM53UC then AAN/A – UC in remission for years prior to tofacitinib for AATofacitinib 5 mg BID, 42 monthsNone100/55UCF35UnknownNTofacitinib 15 mg QD, 5 monthsNone100/100Atopic dermatitis, juvenile RA6UCF62UC then AAN/A – UC inactive prior to tofacitinib for AA (s/p colectomy)Tofacitinib 5 mg BID, 31 months (taking for RA)None100/100Atopic dermatitis, celiac disease, hypothyroidism, RA7UCF21UC then AAYTofacitinib 5 mg QD (tapered from 10 mg BID), 27 months∗Patient 7 was treated with intralesional triamcinolone as needed, and patient 9 was treated with minoxidil 2.5 mg twice daily plus intralesional triamcinolone as needed.Vedolizumab100/0Atopic dermatitis8UCM50AA then UCYTofacitinib 5 mg BID (tapered from 10 mg BID), 24 monthsNone50/09UCM37UC then AAYTofacitinib 10 mg BID, 14 months∗Patient 7 was treated with intralesional triamcinolone as needed, and patient 9 was treated with minoxidil 2.5 mg twice daily plus intralesional triamcinolone as needed.Infrequent mesalamine99/15VitiligoAA, Alopecia areata; BID, twice a day; Dx, diagnosis; F, female; IBD, inflammatory bowel disease; JAK, Janus kinase; M, male; N, no; N/A, not available; QD, daily; RA, rheumatoid arthritis; SALT, severity of alopecia tool; s/p, status post; UC, ulcerative colitis; Y, yes.∗ Patient 7 was treated with intralesional triamcinolone as needed, and patient 9 was treated with minoxidil 2.5 mg twice daily plus intralesional triamcinolone as needed. Open table in a new tab AA, Alopecia areata; BID, twice a day; Dx, diagnosis; F, female; IBD, inflammatory bowel disease; JAK, Janus kinase; M, male; N, no; N/A, not available; QD, daily; RA, rheumatoid arthritis; SALT, severity of alopecia tool; s/p, status post; UC, ulcerative colitis; Y, yes. This study was limited by the relatively small number of patients, possible selection bias, and generalizability, as the patients came from a single provider clinic. Autoimmune comorbidities are common in patients with AA. While it is unknown how often IBD and AA co-occur in the same patient, in our experience IBD (UC, in particular) is not rare in patients with AA. Indeed, the pathobiology of AA and IBD may overlap,1Xing L. Dai Z. Jabbari A. et al.Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition.Nat Med. 2014; 20: 1043-1049Crossref PubMed Scopus (454) Google Scholar, 2Salas A. Hernandez-Rocha C. Duijvestein M. et al.JAK–STAT pathway targeting for the treatment of inflammatory bowel disease.Nat Rev Gastroenterol Hepatol. 2020; 17: 323-337Crossref PubMed Scopus (96) Google Scholar, 3Festen E.A.M. Goyette P. Scott R. et al.Genetic variants in the region harbouring IL2/IL21 associated with ulcerative colitis.Gut. 2009; 58: 799-804Crossref PubMed Scopus (118) Google Scholar, 4Petukhova L. Duvic M. Hordinsky M. et al.Genome-wide association study in alopecia areata implicates both innate and adaptive immunity.Nature. 2010; 466: 113-117Crossref PubMed Scopus (479) Google Scholar and data support a therapeutic role for JAK inhibitors in the treatment of both diseases.1Xing L. Dai Z. Jabbari A. et al.Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition.Nat Med. 2014; 20: 1043-1049Crossref PubMed Scopus (454) Google Scholar,2Salas A. Hernandez-Rocha C. Duijvestein M. et al.JAK–STAT pathway targeting for the treatment of inflammatory bowel disease.Nat Rev Gastroenterol Hepatol. 2020; 17: 323-337Crossref PubMed Scopus (96) Google Scholar,5Liu L.Y. Craiglow B.G. Dai F. King B.A. Tofacitinib for the treatment of severe alopecia areata and variants: a study of 90 patients.J Am Acad Dermatol. 2017; 76: 22-28Abstract Full Text Full Text PDF PubMed Scopus (159) Google Scholar Indeed, our data show successful treatment of both IBD and AA in a small cohort of patients. It is notable that the majority of the patients had UC, and clinical trial data supports use of tofacitinib for patients with UC. The one patient with Crohn disease also responded, but, in general, there is conflicting evidence regarding the treatment of Crohn disease with tofacitinib. Therapeutic decision-making can be complex in patients with multiple autoimmune diseases, such as AA and IBD. In such patients, it would be preferable to treat more than 1 disease with a single agent. Toward this end, JAK inhibitors should be considered in patients with comorbid AA and IBD.