Characteristics,Management,and Outcomes of Latent Tuberculosis Reactivation Following the Use of Biologics for Psoriasis: A Systematic Review

Abstract

Keywords

Mycobacterium tuberculosis TB reactivation biologics psoriasis TNF-alpha inhibitors IL-17 inhibitors IL-23 inhibitors IL-12/23 inhibitors

To the Editor,

Biologics have shown favourable efficacy and safety in treating psoriasis. However, increasing reports of latent Mycobacterium tuberculosis (TB) reactivation have emerged in association with these therapies.^1,2 This systematic review examines the characteristics, management, and outcomes of TB reactivation in patients receiving biologics for psoriasis.

Following PRISMA guidelines, Embase and MEDLINE databases were searched using specific keywords (Supplemental Table I). Study quality was appraised using the Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence. After independent screening by 2 reviewers, 22 articles were included, encompassing 34 patients (Supplemental Figure 1 and Supplemental Table II). Evidence included randomized controlled trials (45.5%, 10/22), cohort studies (4.5%, 1/22), and case reports (50%, 11/22).

Among studies reporting demographic data, the mean patient age was 48.9 years (range: 27-79), with 66.7% (16/24) identifying as female and 33.3% (8/24) as male (Supplemental Table III). Most patients (83.9%; 26/31) had confirmed positive TB screening results, and 66.7% (22/33) received TB prophylaxis, primarily with isoniazid monotherapy (77.8%, 14/18). Only 2 patients (5.9%) received Bacillus Calmette–Guérin vaccinations. Extrapulmonary TB cases were more commonly reported (61.5%; 16/26) than pulmonary TB (38.5%; 10/26).

The mean duration from biologic initiation to TB reactivation was 445.2 days. Among patients, 14.7% (5/34) used prior biologic therapies, and 32.4% (11/34) received previous systemic treatments. Following reactivation, 47.1% (16/34) discontinued biologics, while 1 patient (2.9%) continued ustekinumab. Adalimumab was the biologic most commonly associated with TB reactivation, occurring in 26.5% of cases (9/34). Other biologics included etanercept (20.6%, 7/34), infliximab (17.6%, 6/34), secukinumab (14.7%, 5/34), ustekinumab (8.8%, 3/34), ixekizumab (2.9%, 1/34), and guselkumab (2.9%, 1/34). Two cases used combination therapies, involving etanercept with efalizumab (2.9%, 1/34) and etanercept with adalimumab (2.9%, 1/34).

TB resolution was achieved in 56.3% of cases (18/32), with the rifampin, isoniazid, pyrazinamide, and ethambutol (RIPE) regimen leading to resolution in 83.3% of those treated with it (10/12). The average treatment duration was 31.9 weeks. Psoriasis relapse was noted in 4 (12.5%) cases, primarily with RIPE therapy (16.7%, 2/12). No cases of TB reactivation were reported post-resolution. Adverse effects were uncommon, with one (3.1%) case reporting pyrazinamide-related intolerance and another (3.1%) reporting right anterior uveitis and bilateral retinal vasculitis during RIPE therapy. The mean follow-up period was 18.7 months.

Our findings highlight several cases of latent TB reactivation in patients receiving biologics for psoriasis, particularly TNF-α inhibitors. TNF-α is essential for granuloma formation and maintenance, which helps contain latent TB.³ Its inhibition compromises granuloma integrity, increasing the risk of reactivation.³ We also observed reactivation with IL-17, IL-23, and IL-12/23 inhibitors. IL-17 facilitates neutrophil recruitment and mucosal immunity, while IL-23 promotes IFN-γ production by innate-like lymphocytes, which are important for mycobacterial containment.^4,5 By disrupting these immune pathways, these agents may increase the risk of reactivation.^4,5 Although the RIPE regimen often led to resolution, cases of psoriasis relapse after treatment emphasize the need for tailored strategies to manage both conditions effectively.

Study limitations include incomplete follow-up data and potential selection bias. Nonetheless, our findings emphasize the need for clinical vigilance when using biologics in patients with latent TB. Further research is needed on this phenomenon and management strategies.

Supplemental Material

sj-docx-1-cms-10.1177_12034754251351851 – Supplemental material for Characteristics, Management, and Outcomes of Latent Tuberculosis Reactivation Following the Use of Biologics for Psoriasis: A Systematic Review

Supplemental material, sj-docx-1-cms-10.1177_12034754251351851 for Characteristics, Management, and Outcomes of Latent Tuberculosis Reactivation Following the Use of Biologics for Psoriasis: A Systematic Review by Darshana Seeburruth, Jazlyn McGuinty, Siddhartha Sood, Tatiana Lapa, Edgar Akuffo-Addo and Vincent Piguet in Journal of Cutaneous Medicine and Surgery

Supplemental Material

sj-docx-2-cms-10.1177_12034754251351851 – Supplemental material for Characteristics, Management, and Outcomes of Latent Tuberculosis Reactivation Following the Use of Biologics for Psoriasis: A Systematic Review

Supplemental material, sj-docx-2-cms-10.1177_12034754251351851 for Characteristics, Management, and Outcomes of Latent Tuberculosis Reactivation Following the Use of Biologics for Psoriasis: A Systematic Review by Darshana Seeburruth, Jazlyn McGuinty, Siddhartha Sood, Tatiana Lapa, Edgar Akuffo-Addo and Vincent Piguet in Journal of Cutaneous Medicine and Surgery

Supplemental Material

sj-docx-3-cms-10.1177_12034754251351851 – Supplemental material for Characteristics, Management, and Outcomes of Latent Tuberculosis Reactivation Following the Use of Biologics for Psoriasis: A Systematic Review

Supplemental material, sj-docx-3-cms-10.1177_12034754251351851 for Characteristics, Management, and Outcomes of Latent Tuberculosis Reactivation Following the Use of Biologics for Psoriasis: A Systematic Review by Darshana Seeburruth, Jazlyn McGuinty, Siddhartha Sood, Tatiana Lapa, Edgar Akuffo-Addo and Vincent Piguet in Journal of Cutaneous Medicine and Surgery

Supplemental Material

sj-docx-4-cms-10.1177_12034754251351851 – Supplemental material for Characteristics, Management, and Outcomes of Latent Tuberculosis Reactivation Following the Use of Biologics for Psoriasis: A Systematic Review

Supplemental material, sj-docx-4-cms-10.1177_12034754251351851 for Characteristics, Management, and Outcomes of Latent Tuberculosis Reactivation Following the Use of Biologics for Psoriasis: A Systematic Review by Darshana Seeburruth, Jazlyn McGuinty, Siddhartha Sood, Tatiana Lapa, Edgar Akuffo-Addo and Vincent Piguet in Journal of Cutaneous Medicine and Surgery

Supplemental Material

sj-docx-5-cms-10.1177_12034754251351851 – Supplemental material for Characteristics, Management, and Outcomes of Latent Tuberculosis Reactivation Following the Use of Biologics for Psoriasis: A Systematic Review

Supplemental material, sj-docx-5-cms-10.1177_12034754251351851 for Characteristics, Management, and Outcomes of Latent Tuberculosis Reactivation Following the Use of Biologics for Psoriasis: A Systematic Review by Darshana Seeburruth, Jazlyn McGuinty, Siddhartha Sood, Tatiana Lapa, Edgar Akuffo-Addo and Vincent Piguet in Journal of Cutaneous Medicine and Surgery

Supplemental Material

sj-pdf-6-cms-10.1177_12034754251351851 – Supplemental material for Characteristics, Management, and Outcomes of Latent Tuberculosis Reactivation Following the Use of Biologics for Psoriasis: A Systematic Review

Supplemental material, sj-pdf-6-cms-10.1177_12034754251351851 for Characteristics, Management, and Outcomes of Latent Tuberculosis Reactivation Following the Use of Biologics for Psoriasis: A Systematic Review by Darshana Seeburruth, Jazlyn McGuinty, Siddhartha Sood, Tatiana Lapa, Edgar Akuffo-Addo and Vincent Piguet in Journal of Cutaneous Medicine and Surgery

Footnotes

Data Availability

Data available upon request to the corresponding author.

Declaration of Conflicting Interests

The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The authors Ms. Seeburruth, Ms. McGuinty, Mr. Sood, Dr. Lapa, and Dr. Akuffo-Addo have no conflicts of interest to declare. Dr. Piguet has received grants from AbbVie, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Incyte, Janssen, LEO Pharma, L’Oréal, Novartis, Organon, Pfizer, Sandoz, and Sanofi; received payment or honoraria for speaking engagement from Sanofi; participated on an advisory board for LEO Pharma, Novartis, Sanofi, Union Therapeutics, Abbvie, and UCB; and received equipment donation from L’Oréal.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iDs

Darshana Seeburruth

Siddhartha Sood

Edgar Akuffo-Addo

Vincent Piguet

Supplemental Material

Supplemental Material for this article is available online.

References

Lopez-Trujillo

Pesqué

Sanchez

, et al. Active tuberculosis in a cohort of patients with psoriasis on biologic therapy: learnings from real-life medical practice. J Eur Acad Dermatol Venereol. 2022;36(9):e689-e691. doi:10.1111/jdv.18131

Yuan

Lin

, et al. Safety of biologics for psoriatic patients with latent tuberculosis. Clin Cosmet Investig Dermatol. 2023;16:2333-2336. doi:10.2147/ccid.s426253

Lin

Plessner

Voitenok

Flynn

. Tumor necrosis factor and tuberculosis. J Investig Dermatol Symp Proc. 2007;12(1):22-25. doi:10.1038/sj.jidsymp.5650027

Philippot

Ogishi

Bohlen

, et al. Human IL-23 is essential for IFN-γ–dependent immunity to mycobacteria. Sci Immunol. 2023;8(80):eabq5204. doi:10.1126/sciimmunol.abq5204

Torrado

Cooper

. IL-17 and Th17 cells in tuberculosis. Cytokine Growth Factor Rev. 2010;21(6):455-462. doi:10.1016/j.cytogfr.2010.10.004

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.01 MB

0.11 MB

0.01 MB

0.03 MB

0.00 MB