Background: Interstitial lung disease (ILD) is a common extra-articular manifestation of rheumatoid arthritis (RA). The increase in all-cause mortality following ILD development in patients with RA who have initialised treatment with a biologic/targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD), and how it relates to the corresponding increase in the general population following incident ILD, remains unknown.

Objectives: To assess and compare the five-year mortality in RA patients with and without ILD, and in the general population with and without ILD.

Methods: Patients with RA initiating a first b/tsDMARD were identified from rheumatology registers from Denmark, Finland, Iceland, Norway and Sweden. General population subjects were available from four countries. Incident ILD (index cases) were identified through linkage to national hospital registers and defined as two or more hospital registration of an ICD10-code for ILD. Cases with ILD prior to date of study inclusion, were excluded. All-cause mortality was assessed through Cause of Death registers. Each case of incident ILD in the RA cohort was matched to five age-, gender- and country matched RA subjects who had not been diagnosed with incident ILD during the observation period. Similarly, subjects in the general population with incident ILD were matched to five subjects free from ILD. Baseline for each group of index case and 5 matched controls was defined as the time-point when the index case received the second ILD-diagnosis. For each of the four cohorts (RA with and without ILD, general population with and without ILD), we calculated the crude mortality during a maximum of five years of follow-up, and compared these using Cox regression, taking age at baseline, sex and country into account.

Results: A total of 239 cases of incident ILD in the RA cohort were matched to 1,195 RA patients without ILD. 378 population subjects with incident ILD were matched to 1,890 subjects without ILD (Table 1). At baseline, 995 (69%) of all 1,434 RA patients were treated with b/tsSDMARD (678 (47%) on TNF inhibitors, 155 (11%) on Rituximab, 162 (11%) on other b/tsDMARDs).

During a 5-year follow-up from baseline, 187 of the patients with RA and 236 in the general population died, respectively (Figure 1). Compared to background risk, among those with RA, ILD conferred a three-fold increase in all-cause mortality (HR=3.6 (2.6, 4.8)), while in the general population, ILD conferred an eight-fold increase (HR=8.3 (6.4, 10.8)) (Table 1). The interaction term for RA and ILD revealed a lower all-cause mortality than expected from each of RA and ILD (p for interaction < 0.001).

Figure 1.

RA; rheumatoid arthritis, ILD; Interstitial lung disease

Conclusion: ILD confers a substantial increase in mortality in RA patients as well as in the general population, but combination of the two (RA and ILD) does not increase mortality beyond that expected from each factor. The difference in mortality of ILD in b/tsDMARD treated RA patients and in the general population could reflect different subtypes of ILD, referral bias, or with a selection bias in RA patients included.

REFERENCES: NIL.

Acknowledgements: NIL.

Disclosure of Interests: Sella Aarrestad Provan Pfizer and Boehringer Ingelheim, Boehringer Ingelheim, Eirik Ikdahl: None declared, Lotta Ljung SRQ has through Karolinska University hospital during the last five years entered agreements with Abbvie, Amgen, Eli Lilly, Galapagos, Novartis, Pfizer, Sanofi, Sobi, UCB, Janssen, BMS, GSK, and Otsuka, with the register holder for SRQ as the principal investigator., Brigitte Michelsen Novartis Research grant paid to employer, Till Uhlig Galapagos, Lilly, Pfizer, SOBI, UCB, Thorarinn Jonmundsson: None declared, Joe Sexton: None declared, Bjorn Gudbjornsson Novartis,

Nordic-Pharma, Novartis, Daniela Di Giuseppe: None declared, Merete Lund Hetland Pfizer, Medac, Sandoz (No personal income, paid to institution), MLH has chaired the steering committee of the Danish Rheumatology Quality Registry (DANBIO, DRQ), which receives public funding from the hospital owners and funding from pharmaceutical companies. MLH co-chairs EuroSpA, which generates real-world evidence of treatment of psoriatic arthritis and axial spondylorthritis based on secondary data and is partly funded by Novartis. Advisory board: Abbvie (No personal income, paid to institution), Reserach grant paid to institution: AbbVie, Biogen, BMS,Celltrion, Eli Lilly, Janssen Biologics B.V, Lundbeck Foundation, MSD, Pfizer, Roche, Samsung Biopies, Sandoz, Novartis. Research Grant. Institutions: Nordforsk Research Grant, institution, Lene Dreyer Contract with BMS and Abbvie outside the present work (payment to Department), Janssen UCB Boehringer Ingelheim, Guðrún Björk Reynisdóttir: None declared, Bente Glintborg BMS, Sandoz, AbbVie. Research grants paid to institution, Heikki Relas UCB, Abbvie, Pfizer, Mylan, Janssen, Kalle Aaltonen: None declared, Tore K. Kvien Grünenthal, Sandoz], NOR-DMARD supported by AbbVie, BMS, Galapagos, Novartis, Pfizer and UCB, TKK has received consultancy fees from: AbbVie, Gilead, Janssen, Novartis, Pfizer, Sandoz, UCB], Johan Askling Abbvie, BMS, Eli Lilly, Galapagos, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi. Agreements between Karolinska Institutet (with JA as PI) and the listed entities, mainly for the national safety monitoring of rheumatology immunomodulators in Sweden (ARTIS).