Short-term response in new users of anti-TNF predicts long-term productivity and non-disability: analysis of Czech ATTRA ankylosing spondylitis biologic registry

ABSTRACT

Objectives: To assess the role of short-term response to first anti-TNF in long-term prediction of disability.

Methods: In nationwide registry ATTRA, we identified ankylosing spondylitis patients starting anti-TNF between 01/2003 and 12/2016. Full disability and work impairment (WI; WPAI questionnaire) were predicted via the Cox- and lagged-parameter mixed-effect regression.

Results: 2,274 biologicals-naïve patients newly indicated to anti-TNF were prospectively followed (6,333 patient-years; median follow-up 1.9 years). Reaching BASDAI < 4 (77.4%) and ASDAS-CRP < 2.1 (61.1%) after 3 months of anti-TNF both decreased the risk of future disability by ≈2.5-fold. ASDAS-CRP < 2.1 predicted non-disability better than BASDAI < 4 & CRP < 5 mg/L (p = 0.032). BASDAI < 4 & CRP < 5 mg/L was comparable to BASDAI < 4 (p = 0.941) and to BASDAI change by >50% or by >2 points (p = 0.902). ASDAS-CRP change >1.1 and >2.0 both failed to predict non-disability. Once on anti-TNF therapy, the strongest predictor of WI was Pain (SF36). Yearly increase in indirect costs remains below €3,000 in those reaching ASDAS-CRP < 2.1.

Conclusions: Low disease activity measured by ASDAS-CRP ≤ 2.1 should be used to measure the outcome of new anti-TNF therapy. Continuous WI could be decreased through pain management.

KEYWORDS:

• Ankylosing spondylitis
• BASDAI
• ASDAS
• anti-TNF
• work impairment
• disability
• predictive power
• multivariate modeling

Author contributions

Jakub Závada managed the registry. Tomáš Doležal, Jiří Vencovský, and Karel Pavelka prepared the protocol for data extraction. Lucie Nekvindová, Zlatuše Křístková, Michal Svoboda, and Michal Uher had access to the registry and extracted the data for analysis according to the protocol. Jan Tužil, Tomáš Mlčoch, and Tomáš Doležal wrote the manuscript and Jan Tužil had primary responsibility for the final content. Jan Tužil designed the statistical analysis. Jan Tužil and Jitka Jirčíková prepared and analyzed the data. Lucie Nekvindová, Zlatuše Křístková, Michal Svoboda, and Michal Uher performed the statistical review, Tomáš Mlčoch performed the HTA review, Tomáš Doležal, Jakub Závada, and Karel Pavelka all worked on the continuous medical review of the manuscript.

Patient involvement

Patient consent with collection and processing of personal information was signed at the inclusion into the ATTRA-AS by each patient. Patients had the right to withdraw from the registry, for any reason, at any time. The handling of personal information followed Regulation (EU) 2016/679 and (CZ) Act No. 101/2000 Coll. Patients reported on their quality of life, disease burden, and work impairment at any visit during the interview with their treating physician and also via paper questionnaires. Patients are aware of the scientific purpose of the registry. The results of analyses from ATTRA are communicated via publications for both medical and lay public. More details on http://attra.registry.cz/index.php?pg=gdpr.

NCA and ethics approval

Project ATTRA was approved and is supervised by multicentric ethics committee and competent authority under the identifier 1011290000. All records are anonymized. Personal data include birth date, gender, and initials.

Declaration of interest

K Pavelka has received honoraria for lectures and consultations from Roche, AbbVie, MSD, BMS, Pfizer, Biogen, and UCB. J Vencovský has received honoraria for lectures and consultations from AbbVie, Biogen, Eli Lilly, GSK, MSD, Novartis, Pfizer, Roche, Sanofi, UCB. J Závada has received honoraria for lectures and consultations from AbbVie, Elli-Lilly, BMS, Pfizer, Biogen, and UCB. There was no financial reward related to this article. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

The supplementary data for this article can be accessed here.

Notes

1. Diagnosis of AS according to the modified New York or ASAS criteria; disease activity BASDAI ≥ 4 at two consecutive checkups in a period of at least 4 weeks; CRP > 10 mg/l; failure of conventional therapy in patients with polyarthritis (4 weeks of NSAIDs, 6 months of sulfasalazine); 1 glucocorticoid local injection for monoarthritis; positive expert opinion; absence of a contraindication for treatment [36].

2. Patients with partial disability (n = 66) were considered to remain at-risk of complete disability.

3. Stage 2 prior to 2010 and stage 3 after 2010.

4. Note that patients indicated for anti-TNF represent a specific subset, where advanced disease states were more prevalent compared to average AS patients.

5. Mann–Whitney test for absolute change adjusted for age and calendar year at anti-TNF therapy initiation, gender, baseline disease duration, and also disease activity and stage at visits 1 and 2 (using CRP, BASDAI and radiological staging). Baseline cohort characteristics stratified by radiological stage (0–5) are available as online Supplementary Table 2.

Additional information

Funding

The work of the authors was supported by the Czech Ministry of Health – Conceptual Development of Research Organization 00023728 (Institute of Rheumatology).