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It remains a great challenge to treat the complexity of systemic rheumatic diseases in clinical practice. In contrast to what one may think, these challenges are not so much related to a lack of eff ective treatments, as many powerful drugs are available for treating rheumatoid arthritis, many of which became licensed over the course of the past decade [1]. Th e use of any of these new - as well as of the ‘older’ - drugs is scientifi cally based on results of randomized controlled trials. Th e classical design of these trials, however, is what makes the step into clinical practice so challenging. With the strict inclusion and exclusion criteria of these trials, the patient populations tested in those trials are in sharp contrast to patients requiring treatment in clinical practice. Th is is further supported by the fact that only a fraction of patients in a rheumatology practice would fulfi ll the criteria to enter phase II/III trials [2]. A central reason for this is that patients with potential risk factors for an adverse reaction to an investigative drug are excluded from the beginning to make the trial safer; but this group of patients constitutes a large portion of those who will ultimately require treatment in clinical practice. Until the recent calls for more pragmatic trials [3] that address patient populations with all the risk factors faced in daily practice have manifested in actual trial designs, physicians will often need to make their own decisions, weighing expected (but sometimes unknown) risks against the possible benefi ts. Although a number of management guidelines for

Considering comorbidity in managing rheumatic diseases: going where trials cannot go