Rheumatoid arthritis (RA) is a chronic rheumatic disease that affects approximately 0.5%–1% of the adult population. It leads to functional disability, affects many organs, worsens the quality of life, and increases the risk of premature death.1 The disease and its treatment are associated with high medical and social costs. So far, the etiopathogenesis of RA has not been fully elucidated2 and a complete cure of the disease is still not achievable.3
However, significant progress has been made in pharmacological treatment. A number of potent biological disease-modifying antirheumatic drugs (bDMARDs), mainly cytokine blockers, have been introduced in addition to conventional disease-modifying drugs (csDMARDs), such as methotrexate (Mtx), leflunomide, sulfosalazine, or hydroxychloroquine. Furthermore, in the last 5 years targeted synthetic DMARDs (tsDMARDs) that are Janus kinase inhibitors have become available.3,4 Glucocorticosteroids and symptomatic drugs, mainly non-steroidal anti-inflammatory drugs, are used frequently all the time. The current management recommendations reflect the balance of clinical efficacy, safety, and costs of treatment, and indicate remission or low disease activity as the treatment target (treat to target strategy [T2T]).5,6 So far, this has not been an easy goal to achieve. Moreover, the remission in RA can be defined in various ways.7 In daily routine, remissions are usually defined by disease activity scores, such as disease activity score using 28 joint count (DAS 28), Clinical Disease Activity Index (CDAI), Simple Disease Activity Index, and less frequently by the Boolean-based European League Against Rheumatism / American College of Rheumatology criteria.5,7 The most beneficial and difficult to achieve is sustained drug-free remission, lasting at least 6 months without progressive joint destruction.8
We currently use a group of drugs with different mechanisms of action and follow the evidence-based recommendations for therapeutic management,5,6 but do we achieve the assumed therapeutic goals in everyday practice in a given country?
Randomized clinical trials (RCTs) of consecutive bDMARDs and tsDMARDs with Mtx as a comparator, conducted in carefully selected groups of RA patients indicated the possibility of achieving remission in the Mtx monotherapy group in an average of about 28% (7.6%–50%) of patients after 24–26 weeks, while bDMARDs and tsDMARDs induced the remission in about 40% to 60% of patients.9 Patient selection criteria, concomitant medication, remission definitions (DAS 28 ≤2.6, CDAI ≤2.8, etc.), and other factors in RCTs are different and the comparison of results is often questionable. A better analysis of the effectiveness and safety of treatment is provided by large, comprehensive national registers,4,8 which mainly concern groups of patients receiving second-line therapies with expensive bDMARDs and tsDMARDs, while data on the effectiveness of treatment of most RA patients with commonly used csDMARDs in the real world are rather limited or derived from older studies.9-11
In this issue of Polish Archives of Internal Medicine, Batko et al12 present a prospective observational study evaluating the actual effectiveness of treatment with csDMARDs in routine RA care conducted by 82 rheumatologists in Poland. The rates of low disease activity and remission achieved at 3 and 6 months in a cohort of 780 outpatients with RA were assessed. The authors, however, did not investigate the efficacy of individual DMARDs. Their aim was to identify potential clinical and demographic predictors conducive to achieving the therapeutic target, that is, DAS 28 below or equal to 3.2. It turned out that after 3 months of treatment, 9% of the patients achieved remission or low disease activity, and after 6 months either of these were achieved in 35% of patients. Compared with other reports, the rate of adequate disease control was shown to be low.12
The negative effects of undoubtedly important factors reported by Batko et al,12 such as smoking or BMI above 25 kg/m2 on achieving the therapeutic target do not appear to sufficiently explain why 65% of the patients did not achieve the T2T goals. When delving into the analysis of the causes of the treatment failure, it seems most desirable to investigate the impact of the missing factors, such as the dosage and route of Mtx administration (because underuse of Mtx at doses below 15 mg/week is quite common)13, and the dosing of other csDMARDs, presence of early erosions, comedication, and comorbidities, that is, an important factor in daily practice, almost eliminated in drug RCTs.14,15 It is also unclear if any treatment-naive patients were enrolled by Batko et al.12 It could have mattered because “a percentage of patients fails one or more DMARDs, before achieving remission.”3 It would also be worth answering the question whether all of the 82 rheumatologists participating in the study followed the current recommendations and the T2T strategy,5 and whether the patient compliance was sufficient. Finding the right answers to these questions is essential, because in many countries, as in Poland, the overwhelming majority of RA patients are treated with csDMARDs only, and access to bDMARDs and tsDMARDs is very limited.
Real-life studies assessing the effectiveness of treatment of this chronic rheumatic disease are highly desirable, and the work of Batko et al12 provides valuable information and corroborates investigations seeking ways to definitely improve the outcomes of our current therapy for RA. Undoubtedly, the implementation of the T2T strategy in daily care is crucial. There is also a hope that much better access to bDMARDs and tsDMARDs for RA patients, the adoption of personalized medicine principles in our daily routine, and possibly the implementation of machine learning prediction models in the future may change our treatment outcomes.3
Piotr Głuszko, MD, PhD, National Institute of Geriatrics, Rheumatology and Rehabilitation, ul. Spartańska 1, 02-637 Warszawa, Poland, phone: +48 12 670 92 12, email: zruj@mp.pl
September 1, 2022.
September 2, 2022.
September 26, 2022.
The opinions expressed by the author(s) are not necessarily those of the journal editors, Polish Society of Internal Medicine, or publisher.
None declared.
Głuszko P. The news is clear: real-life studies show the actual effectiveness of treatment. Pol Arch Intern Med. 2022; 132: 16338. doi:10.20452/pamw.16338
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