(1) Background: Gut microbiota (GM) is the set of microorganisms inhabiting the gastroenteric tract that seems to have a role in the pathogenesis of rheumatic diseases. Recently, many authors proved that GM may influence pharmacodynamics and pharmacokinetics of several drugs with complex interactions that are studied by the growing field of pharmacomicrobiomics. The aim of this review is to highlight current evidence on pharmacomicrobiomics applied to the main treatments of Rheumatoid Arthritis and Spondyloarthritis in order to maximize therapeutic success, in the framework of Personalized Medicine. (2) Methods: We performed a narrative review concerning pharmacomicrobiomics in inflammatory arthritides. We evaluated the influence of gut microbiota on treatment response of conventional Disease Modifying Anti-Rheumatic drugs (cDMARDs) (Methotrexate and Leflunomide) and biological Disease Modifying Anti-Rheumatic drugs (bDMARDs) (Tumor necrosis factor inhibitors, Interleukin-17 inhibitors, Interleukin 12/23 inhibitors, Abatacept, Janus Kinase inhibitors and Rituximab). (3) Results: We found a great amount of studies concerning Methotrexate and Tumor Necrosis Inhibitors (TNFi). Conversely, fewer data were available about Interleukin-17 inhibitors (IL-17i) and Interleukin 12/23 inhibitors (IL-12/23i), while none was identified for Janus Kinase Inhibitors (JAKi), Tocilizumab, Abatacept and Rituximab. We observed that microbiota and drugs are influenced in a mutual and reciprocal way. Indeed, microbiota seems to influence therapeutic response and efficacy, whereas in the other hand, drugs may restore healthy microbiota. (4) Conclusions: Future improvement in pharmacomicrobiomics could help to detect an effective biomarker able to guide treatment choice and optimize management of inflammatory arthritides.
BackgroundThe course of systemic sclerosis associated interstitial lung disease (SSc-ILD) is highly variable. The SSc-ILD progression (SILPRO) project aims at developing a disease specific model to define SSc-ILD progression predicting long-term, severe SSc-ILD. The evaluation of currently used definitions of severity, progression and outcomes recorded in SSc-ILD represents the highly needed first step to achieve this aim.ObjectivesTo identify definitions of progression, severity and outcomes related to SSc-ILD in the literature.MethodsA systematic literature review was conducted according to PRISMA guidelines in Medline, EMBASE and the Cochrane Library up to 31/12/2021. Eligible papers included > 10 adult SSc patients, with ILD as primary target (at least one of population, exposure, outcome). Original papers in English were considered, while papers related to secondary lung involvement, ILD onset as an outcome or reviews were excluded. Two reviewers independently identified eligible studies and extracted data, including the abovementioned definitions used.ResultsWe identified 299/8444 eligible papers, mostly reporting results of retrospective cohort studies (n=126, 42%), prospective cohort studies (n=120, 40%) and randomized clinical trials (n=24, 8%).A definition of SSc-ILD severity was included in 138 (46%) papers: it was based on high-resolution computed tomography (HRCT) data in 72 (52%) studies, on forced vital capacity (FVC) changes in 29 (21%), on combined FVC and carbon monoxide diffusing capacity (DLCO) changes in 14 (10%), on DLCO changes in 11 (8%). After combining some similar categories, 42 distinct definitions of SSc-ILD severity were identified (Figure 1 shows the most used).Figure 1.Most commonly used definitions of SSc-ILD severity (n papers).Sixty-one of 169 studies (36%) provided a definition of SSc-ILD “progression” referred to combined DLCO and FVC changes, 49 (29%) to FVC changes, 23 (14%) to DLCO changes, 18 (11%) to ILD extent on HRCT, 6 (4%) to combination of pulmonary function test (PFT), clinical signs and HRCT data, 5 (3%) to vital capacity decline, 5 (3%) to combination of PFT and HRCT data and 2 (1%) to other aspects (Table 1).Table 1.Most frequently used definitions of SSc-ILD progressionSSc mixed cohortsSSc-ILD cohortsTime, months(n papers)n patients (n papers)n ILD patients (n papers)n progressors(n papers)Time, months(n papers)n patients (n papers)n progressors (n papers)decline FVC>10%12 (8)24 (3)36 (3)>60 (2)Unk (3)3347 (17)1779 (16)605 (17)6 (3)12 (3)24 (4)>60 (4)1544 (14)263 (13)decline FVC>5%Unk (1)138 (1)100 (1)49 (1)12 (2)24 (1)Unk (1)836 (4)179 (3)decline FVC>3.3%----12 (2)Unk (1)734 (2)349 (2)decline DLCO>15%12 (2)24 (1)60 (2)568 (5)445 (5)135 (5)6 (2)12 (2)36 (1)60 (2)505 (7)168 (7)decline DLCO>10%12 (2)55 (1)>60 (1)Unk (2)340 (5)112 (2)86 (5)24 (1)14 (1)9 (1)decline FVC>10% or DLCO>15%6 (1)12 (6)24 (2)>36 (4)>60 (1)Unk (6)6170 (17)2327 (13)1144 (14)12 (8)24 (4)36 (1)>60 (3)Unk (8)1516 (20)449 (16)decline FVC >10% or DLCO>10%6 (1)12 (2)>36 (4)60 (1)531336181 (8)24 (1)36 (2)>36 (2)472 (5)47 (4)decline FVC≥10% or DLCO≥15% or ILD extent increase>20%12 (1)36 (1)24 (1)12 (1)56 (1)58 (1)12 (1)increased ILD extent>10%12 (2)347 (2)213 (2)6 (2)24 (2)145 (2)5 (2)increased ILD extent>20%---24 (1)Unk (1)22 (2)8 (2)increased ILD extent12 (1)37 (1)62 (1)1024 (3)440 (3)99 (3)12 (1)75 (1)34 (1)Among all articles, 47 outcomes related to SSc-ILD were identified from 153 papers. The most frequent outcomes represented hard endpoints, such as mortality (131 papers), end stage lung disease (8 papers), hospitalization (6 papers) and malignancies (4 papers).ConclusionThe studies reporting a definition of SSc-ILD “progression”, “severity” and “outcome” show a large heterogeneity. These results emphasize the need for developing a standardized, consensus definition of severe SSc-ILD, to link a disease specific definition of progression as a surrogate outcome for clinical trials and clinical practice.Acknowledgementson behalf of the SILPRO project investigators.Disclosure of InterestsLiubov Petelytska Grant/research support from: received research grant from Swiss National Research Foundation/Scholars at risk, Francesco Bonomi: None declared, Carlo Cannistrà: None declared, Elisa Fiorentini: None declared, Silvia Peretti: None declared, SARA Torracchi: None declared, Pamela Bernardini: None declared, Carmela Coccia: None declared, Riccardo De Luca: None declared, Alessio Economou: None declared, Juela Levani: None declared, Marco Matucci-Cerinic Speakers bureau: Actelion, Janssen, Inventiva, Bayer, Biogen, Boehringer, CSL Behring, Corbus, Galapagos, Mitsubishi, Samsung, Regeneron, Acceleron, MSD, Chemomab, Lilly, Pfizer, Roche., Consultant of: Actelion, Janssen, Inventiva, Bayer, Biogen, Boehringer, CSL Behring, Corbus, Galapagos, Mitsubishi, Samsung, Regeneron, Acceleron, MSD, Chemomab, Lilly, Pfizer, Roche., Oliver Distler Speakers bureau: 4P-Pharma, Abbvie, Acceleron, Alcimed, Altavant, Amgen, AnaMar, Arxx, AstraZeneca, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galderma, Galapagos, Glenmark, Gossamer, iQvia, Kymera, Lupin, Medscape, Merck, Miltenyi Biotec, Mitsubishi Tanabe; Novartis, Prometheus, Redxpharna, Roivant and Topadur in the area of potential treatments of scleroderma and its complications, Consultant of: 4P-Pharma, Abbvie, Acceleron, Alcimed, Altavant, Amgen, AnaMar, Arxx, AstraZeneca, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galderma, Galapagos, Glenmark, Gossamer, iQvia, Kymera, Lupin, Medscape, Merck, Miltenyi Biotec, Mitsubishi Tanabe; Novartis, Prometheus, Redxpharna, Roivant and Topadur in the area of potential treatments of scleroderma and its complications, Grant/research support from: 4P-Pharma, Abbvie, Acceleron, Alcimed, Altavant, Amgen, AnaMar, Arxx, AstraZeneca, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galderma, Galapagos, Glenmark, Gossamer, iQvia, Kymera, Lupin, Medscape, Merck, Miltenyi Biotec, Mitsubishi Tanabe; Novartis, Prometheus, Redxpharna, Roivant and Topadur in the area of potential treatments of scleroderma and its complications. Research grants: Kymera, Mitsubishi Tanabe, Cosimo Bruni Speakers bureau: Eli-Lilly, Consultant of: Boehringer Ingelheim, Grant/research support from: Gruppo Italiano Lotta alla Sclerodermia (GILS), European Scleroderma Trials and Research Group (EUSTAR), Foundation for research in Rheumatology (FOREUM), Scleroderma Clinical Trials Consortium (SCTC). Educational grants from AbbVie.
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