Reviews & Analysis

Noncommercial, investigator-initiated trials are an essential part of clinical research. In this Viewpoint, the author describes the burden of current legislation on investigator-initiated trials and explores possible solutions.

Emerging data implicate a novel subset of CD4⁺ T cells, termed T_H17 cells, in the pathogenesis of several autoimmune diseases. In this Viewpoint article, the authors discuss the role of T_H17 cells in systemic lupus erythematosus and discuss their potential as a therapeutic target.

Although osteoarthritis is the most common form of joint disease, an effective treatment for this disease is lacking. In this Review, the authors outline the potential use of strategies based on mesenchymal stem cells, which can differentiate into cells of the chondrogenic lineage, in the regeneration and maintenance of damaged articular cartilage.

Systematic reviews, although they can highlight important findings in the literature, often raise even more questions. In this Viewpoint, Prof Smolen and Prof Aletaha discuss approaches to comprehensive reviews in general, and to those involving rheumatoid arthritis in particular, from the clinical trialist's point of view.

Even well-performed systematic reviews do not necessarily provide informative guidance for patient care. In this Viewpoint, Professor Pincus and colleagues argue that evidence from observational research and clinical experience is needed to supplement clinical trials to improve health and outcomes for people with rheumatoid arthritis.

The author of this Viewpoint argues that there is currently insufficient evidence to guide the choice of therapy in rheumatoid arthritis, and highlights the need for large, simple, pragmatic trials designed to determine the best way to treat early or established rheumatoid arthritis, how aggressively to approach comorbidity, and how patients should be monitored.

Signaling from Toll-like receptor (TLR) molecules induces the expression of several molecules that are involved in both innate and adaptive immunity. Targeting TLRs, their co-receptors or their downstream adaptors might be a more selective therapeutic approach for rheumatoid arthritis or systemic lupus erythematosus than inhibiting more global signals, such as nuclear factor κB, as outlined in this Review.

In the treatment of rheumatoid arthritis, where can clinicians find the information to help them decide which drugs to use in what combination and when to use them? In this Viewpoint, the author argues that there is a need to look beyond short-term efficacy studies, and highlights several unanswered questions still to be addressed.

New, noninvasive imaging techniques that can determine various components of bone strength are being developed to assess the risk of fracture in patients with osteoporosis. These techniques, which include three-dimensional assessments of bone density, geometry and microarchitecture, and integrated measurements of bone strength by engineering analyses, are outlined in this article.

Undifferentiated connective tissue disease is characterized by a mild clinical picture, with a low level of disease activity during the entire disease course, and by the absence of manifestations specific to any major connective tissue disease. In this Case Study, Drs Mosca, Tani and Bombardieri present a case of stable undifferentiated connective tissue disease and argue that this condition might constitute a distinct clinical entity.

Drugs that inhibit tumor necrosis factor (TNF) provide considerable benefit in treatment of rheumatoid arthritis (RA); however, there is an unmet medical need for alternative therapies with higher clinical benefit and lower safety risk and cost. The potential to treat RA by targeting TNF-converting enzyme, which promotes the release of soluble TNF from its membrane-bound precursor, is outlined in this Review.

Several randomized controlled trials have investigated the effects of a number of drugs on the reduction of fracture risk in women with postmenopausal osteoporosis. Meanwhile, algorithms have become available to identify women at the highest risk of fractures. In this context, this article outlines patient- and drug-related determinants that contribute to the clinical decision about initiating and choosing drug therapy for the prevention of fractures.

The biology of disc degeneration is complex. Some remarkable advances in molecular and cellular biology have recently been achieved in this rapidly evolving field and biological technologies for intervertebral disc repair are currently being developed. In this Viewpoint, Dr Peng discusses the problems that need to be resolved before these technologies can advance from the laboratory to clinical trials.

Cyclophosphamide is an important therapy for patients with severe rheumatic diseases; it is, however, responsible for gonadal toxicity. There are a number of interventions aimed at reducing this toxicity, including estrogen-containing oral contraceptives, hormone agonists and antagonists of gonadal receptors in females, and testosterone therapy and storage of gametes for male patients. These strategies are outlined in this article.

Palmar fasciitis and polyarthritis syndrome can mimic other rheumatic conditions, and the underlying mechanism for its development has not yet been defined. This syndrome is an uncommon paraneoplastic presentation. In this Case Study, Dr Haroon and Dr Phelan discuss a patient diagnosed with palmar fasciitis and polyarthritis syndrome associated with pancreatic carcinoma.

Early-onset systemic lupus erythematosus (SLE) is thought to be associated with an increased risk to cardiovascular health as well as a severe disease phenotype. As outlined in this article, inflammatory and immune abnormalities that are intrinsic to SLE, primary dyslipidemias and secondary effects of treatments such as corticosteroids, might all contribute to premature atherosclerosis.

Several different surgical treatment options are available to patients with rheumatoid arthritis, with the aims of restoring function and quality of life, preventing joint deterioration, relieving pain, and correcting deformity, as discussed in this article. In addition, a number of factors and specialists should be involved in deciding if and when to proceed with surgical intervention.

A major source of genetic heterogeneity is derived from single base-pair alterations in the DNA sequence. The presence of these single-nucleotide polymorphisms can be measured and analyzed, and can potentially be used, therefore, to investigate genetic heterogeneity, to identify disease-associated variants and, in the future, to develop tailored clinical approaches for individual patients with rheumatic diseases.

Autoimmune inflammatory myopathies are a heterogeneous group of chronic inflammatory muscle diseases that result in progressive inflammatory muscle damage and weakness. As discussed in this Review, damage-induced enhancement of autoantigen expression and adjuvant activity might contribute to pathogenic mechanisms in these diseases.