Methotrexate-Corticosteroid Combo Therapy Tested in JIA

Italian researchers report that concomitant intra-articular corticosteroid plus methotrexate therapy is not superior to intra-articular corticosteroid therapy alone in patients with oligoarticular juvenile idiopathic arthritis. 

Italian researchers report that concomitant intra-articular corticosteroid plus methotrexate therapy is not superior to intra-articular corticosteroid therapy alone in patients with oligoarticular juvenile idiopathic arthritis.

In the study, published online February 2 in The Lancet, the research team explored how, if at all, oral methotrexate could increase the efficacy of intra-articular corticosteroid therapy in children.

Led by Angelo Ravelli, M.D., of the Istituto Giannina Gaslini in Italy, this randomized, open-label trial compared two strategies for treating oligoarticular juvenile idiopathic arthritis, with the primary outcome being remission of arthritis in all injected joints at 12 months.

“The addition of methotrexate did not reduce the prevalence of new onset of synovitis in previously unaffected joints,” wrote Dr. Ravelli and colleagues.

Treating juvenile idiopathic arthritis remains a challenge for rheumatologists because it is a diverse set of diseases with seven mutually exclusive categories. Oligoarticular juvenile idiopathic arthritis accounts for the majority of chronic arthritis in white children and is defined as arthritis that affects four or less joints during the first six months of illness. Although the 2011 recommendations from the American College of Rheumatology address initial plans of treatment for oligoarticular juvenile idiopathic arthritis, the most effective long-term treatment strategies for these patients remain unclear.

Intra-articular corticosteroid injections are commonly used as first-line therapy as a way to provide short-term relief from inflammation and to prevent the need for regular systemic therapy. Despite the efficacy of these injections, most children have recurrence of flares after a period of time.

Prior studies have demonstrated that methotrexate is a mainstay disease-modifying antirheumatic drug for treating juvenile idiopathic arthritis; however, these studies have been conducted with polyarthritis patients. Moreover, although methotrexate is widely-used in children with oligoarthritis, more research is needed on the effects of the drug in this patient population.

The study

This was a prospective, randomized trial conducted with 207 oligoarticular juvenile idiopathic arthritis patients from 10 hospitals in Italy. Children younger than 18 years that were eligible to receive an intra-articular corticosteroid injection in at least two joints were enrolled in the study between July 7, 2009 and March 31, 2013. Patients were randomly assigned (1:1) to intra-articular corticosteroids alone or intra-articular corticosteroids in combination with oral methotrexate (15 mg/m²; maximum 20 mg). Triamcinolone hexacetonide and methylprednisolone were the two corticosteroids used in the study. The primary endpoint was the proportion of patients in the intention-to-treat population who had remission of arthritis in all injected joints at 12 months.

Of the 207 patients in the study, 48 were injected with corticosteroids in one joint and 159 were injected in two or more joints. The main finding was 33 patients (32%) assigned to intra-articular corticosteroids alone and 39 patients (37%) assigned to intra-articular corticosteroids plus methotrexate therapy had remission of arthritis in all injected joints (p=0·48).

“Although our results in the intention-to-treat population were not statistically significant, we feel that these findings lend support to those of previous non-controlled studies and indicate that the outcome of intra-articular corticosteroid therapy might be improved if this procedure was combined with the administration of methotrexate,” wrote Dr. Ravelli and his team.

Disclosures:

Funding

This research was funded by the Italian Agency of Drug Evaluation.

Disclosures

AR reports personal fees from AbbVie, Bristol-Myers Squibb, Novartis, Pfizer, Roche, and Johnson & Johnson. AP reports personal fees from Boehringer, Omniprex, and Novartis. FDB reports grants from

Hoffmann-La Roche, Bristol-Myers Squibb, Novimmune, Novartis, Abbot, Pfizer, and Sobi. NR reports personal fees from AbbVie, Amgen, Biogenidec, Alter, AstraZeneca, Baxalta Biosimilars, Biogenidec,

Boehringer, Bristol-Myers Squibb, Celgene, CrescendoBio, EMD Serono, Hoffman-La Roche, Italfarmaco, Janssen, MedImmune, Medac, Novartis, Novo Nordisk, Pfizer, Sanofi-Aventis, Servier, Takeda, and UCB

Biosciences; and other financial relationships from Bristol-Myers Squibb, GlaxoSmithKline, Hoffman-La Roche, Novartis, Pfizer, Sanofi-Aventis, Schwarz Biosciences, Abbott, Francesco Angelini SPA, Sobi, and Merck Serono. AM reports personal fees from Abbvie, Boehringer, Celgene, CrescendoBio, Janssen, Meddimune, Novartis, NovoNordisk, Pfizer, Sanofi-Aventis, Vertex, and Servier; and other financial relationships from BMS, GlaxoSmithKline, Hoffman-La Roche, Novartis, Pfizer, Sanofi-Aventis, Schwarz Biosciences, Abbott, Francesco Angelini SPA, Sobi, and Merck Serono.

References:

Angelo Ravelli, Sergio Davì, Giulia Bracciolini, et al. "Intra-articular corticosteroids versus intra-articular corticosteroids plus methotrexate in oligoarticular juvenile idiopathic arthritis: a multicentre, prospective, randomised, open-label trial,” The Lancet. Published online February 2, 2017. DOI: 10.1016/S0140-6736(17)30065-X.