Tapering biological agents in rheumatoid arthritis?

Many of my rheumatoid arthritis patients have been taking biological therapy for five or more years, primarily TNF-inhibitors, e.g. adalimumab (Humira). After six months of therapy their symptoms releived, inflammation decreased; later joint damage stopped, physical function and quality of life improved, most of them are even able to work. This clinically asymptomatic state (remission) has been maintained for many years now, and thus the question arises, whether the biological agents can be reduced or even stopped.

Rheumatoid arthritis (RA), which is a chronic inflammatory joint disease, affects 1% of the adult population, and without adequate treatment and management can lead to loss of physical activity and disability.

In the past few years remarkable progress has changed the diagnostic armamentarium and the therapeutic facilities of the disease. Biological therapy has become a reality. In the past, symptomatic treatment was the only possibility, to relieve symptoms, to control inflammation with non-steroid anti-inflammatory drugs and corticosteroids. Later conventional disease modifying agents (eg. methotrexate) arrived and in a way, causal treatment was realized (in the 1980s’), not only were symptoms relieved, but structural damage was prevented. A real breakthrough in therapy was achieved with the introduction of biological drugs* (in the 1990s’), which targeted not only the prevention of structural damage, but preserved physical function, improved quality of life and prevented comorbidities (atherosclerosis, osteoporosis), as well.

*Biological therapy means drugs that are of protein character and are produced by biological methods, they target special molecules or mechanisms of the RA process. The most widely used biological agents today are the tumour necrosis factor-a (TNF-a) inhibitors.

Early aggressive therapy is fundamentally important in the prevention of joint damage, loss of physical activity and poor outcome. Conventional treatment, often based on the GP’s  subjective judgement and experience has been shifted towards evidence-based strategies, such as treat-to-target (T2T) therapy of the disease, targeting remission (**DAS28<2,6) or low disease activity (**DAS28<3,2), on an internationally accepted and standardised scale (**disease activity score). Therapeutic recommendations of the EULAR (European League against Rheumatism) have been built on the strategy above (2010).

DAS28 score

With the application of biological agents and the „treat to target” strategy, remisssion has been achieved and maintained for many years in most of the patients. Tapering has become a reality and must be taken into consideration. According to the renewed therapeutic recommendation of the EULAR (2013), though reducing and stopping corticosteroids remain the first issue, but in the case of a long remission tapering biological agents is also recommended, meaning reducing the dose or increasing the interval. To our knowledge complete stopping of biological drugs – due to the relapse risk – is still not advised. Nevertheless, based on the agreement of the patient’s and his rheumatologist’s decision completion is also allowed. Continuation of the conventional disease modifiers, e.g. low dose methotrexate, is strictly recommended. The longer the remission maintenance is, the more successful tapering biological therapy will be.

As general advice, drug therapy should always be reduced gradually, alongside tight disease control, assessment of therapy should be followed by well-known disease scores (DAS28) and last but not least, only one drug should be reduced at a time.