tacrolimus and laquinimod

With advancement in our understanding of pathogenic mechanisms in systemic lupus erythematosus (SLE), there is tremendous enthusiasm in examining drugs, old and new, to improve outcomes. This review highlights recent trials' successes and impasses that have come to fore.. Among B-cell therapies, belimumab continues its run of successes with sustained safety and tolerability documented in a long-term extension as well as the likely approval of a subcutaneous formulation in the near future. With greater antibody-dependent cytotoxicity and less immunogenicity, there is hope for obinituzumab to succeed where its anti-CD 20 predecessors have failed. Drugs targeting type I interferons - sifalimumab and anifrolumab - have been efficacious albeit with an increase in incidence of Herpes zoster infections. There is also renewed interest in evaluating the efficacy of calcineurin inhibitors, specifically tacrolimus in the induction and maintenance of lupus nephritis. Introspection into clinical trial designs have highlighted the effects of entry criteria, end points, background medications and geographical differences on study outcomes.. There are at least 50 drugs and targets being evaluated in SLE. In addition to developing new drugs to treat lupus, future trials have to focus on more effective study designs to improve chances of trial success.

Topics: Abatacept; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; B-Lymphocytes; Clinical Trials as Topic; Cyclosporine; Herpes Zoster; Humans; Immunosuppressive Agents; Interferon Type I; Lupus Erythematosus, Systemic; Lupus Nephritis; Maintenance Chemotherapy; Peptide Fragments; Plasma Cells; Quinolones; Recombinant Fusion Proteins; Remission Induction; T-Lymphocytes; Tacrolimus; Treatment Outcome

Systemic lupus erythematosus (SLE) is a ripe area for drug development. There are great unmet needs, especially for those with lupus nephritis, in which good responses occur only in the minority of treated patients. An expanded understanding of immunopathogenesis of SLE coupled with the availability of sophisticated bioengineering technologies has resulted in the ability to supply the lupus community with the reagents needed to perform clinical trials. However, drug development in SLE has proven to be particularly challenging. Only one drug, belimumab, has been approved for patients with SLE through the traditional route of randomized controlled trials. The basis for our failures is unknown, but most assuredly relates to trial design issues, confounding by background medicines, and the multiplicity of active biologic pathways in this disease. Off-label use of failed trial drugs such as mycophenolate mofetil and rituximab paradoxically has become routine in many parts of the world. Despite the obstacles, there currently is unprecedented clinical trial activity in lupus nephritis, which most likely will lead to at least one drug approval in years to come.

Topics: Abatacept; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Biological Products; Boron Compounds; Bortezomib; Clinical Trials as Topic; Drug Discovery; Glycine; Humans; Immunologic Factors; Immunosuppressive Agents; Infliximab; Isoxazoles; Leflunomide; Lupus Nephritis; Mycophenolic Acid; Off-Label Use; Oligonucleotides; Quinolones; Recombinant Fusion Proteins; Rituximab; Tacrolimus; Treatment Outcome