Objective Patients with immunological diseases exhibit distinct comorbidity patterns, categorized into low comorbidity, polyautoimmunity, and polyinflammation clusters. This retrospective cohort study aimed to validate these profiles in rheumatoid arthritis (RA), examine their longitudinal trajectories, and assess their impact on treatment persistence.

Methods RA patients receiving targeted therapies, and their associated treatments, were identified from the French pharmacy dispensing database LRx. Comorbidity clusters were assigned using a multinomial regression model, and state sequence analysis with hierarchical clustering was used to define temporal trajectories. Cox regression models evaluated DMARD persistence across trajectories.

Results Among 15,189 RA patients (maximum follow-up: 10 years), initial comorbidity profiles included low comorbidity (61.9%), polyautoimmunity (24.7%), and polyinflammation (13.4%). Four trajectory patterns emerged: stable low comorbidity (50%), dominant polyautoimmune (31%), stable polyinflammatory (9%), and low comorbidity switching to polyinflammation (polyinflammation switchers, 10%). The prevalence of polyautoimmunity and polyinflammation increased with age by 2.5% and 3.8% per decade, respectively.

Patients with stable polyinflammation had the lowest classical synthetic DMARD persistence (HR: 1.79 [1.33–2.42], reference: polyinflammation switchers). Stable low comorbidity patients had the highest biological and targeted synthetic DMARD persistence (polyinflammation switchers aHR: 1.32 [1.09–1.60], reference: stable low comorbidity).

Conclusion Comorbidity trajectories in RA influence DMARD persistence, reflecting distinct etiopathological subgroups with potential theranostic relevance.

Signe Hassler, Julie Aste, Francis Berenbaum, Michelle Rosenzwajg, David Klatzmann and Milka Maravic declare no conflicts of interest. Jeremie Sellam declares consultancies, honoraria, advisory board, and speakers fees from Biogen, Celltrion, Pfizer, BMS, MSD, Abbvie, Lilly, IBSA, Janssen, Novartis, Fresenius Kabi.

This study was supported by Institut Carnot@ AP-HP, by IQVIA and a Laboratory of Excellence grant (n◦ANR-11-IDEX-0004-02).

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The TRANSIMMUNOM study was performed according to the principles of the Helsinki declaration, written informed consent was collected for each patient and the study was approved by the local ethics committee in Ile de France (CPP-IdFVI approval number 48-15). The LRx database was authorized by the French Data Protection Authority (CNIL) on the 21st of October 2011 [reference: DE-2011-097] and updated on July 2018 for compliance with the GDPR [reference: DE-2018-289].

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

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This study was supported by Institut Carnot@ AP-HP, by IQVIA and a Laboratory of Excellence grant (n⍰ANR-11-IDEX-0004-02).

Conflicts of interest:

Signe Hässler, Julie Aste, Francis Berenbaum, Michelle Rosenzwajg, David Klatzmann and Milka Maravic declare no conflicts of interest.

Jérémie Sellam declares consultancies, honoraria, advisory board, and speakers’ fees from Biogen, Celltrion, Pfizer, BMS, MSD, Abbvie, Lilly, IBSA, Janssen, Novartis, Fresenius Kabi.

All data produced in the present study are available upon reasonable request to the authors