Effects of one-year tofacitinib therapy on bone metabolism in rheumatoid arthritis.

Janus kinase (JAK) inhibitors are used to treat rheumatoid arthritis (RA). We assessed the effects of tofacitinib on bone density and bone markers in association with clinical and laboratory parameters in RA. Tofacitinib stabilized bone density and resulted in a positive balance of bone turnover. INTRODUCTION: Janus kinase (JAK) inhibitors emerged as new therapeutic options in rheumatoid arthritis (RA). We have little information on how it affects areal and volumetric bone mineral density (BMD) and bone turnover markers. The aim of this study was to assess the effects of 1-year tofacitinib therapy on bone metabolism in RA. METHODS: Thirty RA patients with active disease were treated with either 5 mg bid or 10 mg bid tofacitinib for 12 months. We determined DAS28, CRP, IgM rheumatoid factor (RF), and anti-cyclic citrullinated peptide (CCP) levels, as well as serum levels of sclerostin, osteocalcin (OC), P1NP, DKK-1, OPG, RANKL, and 25-hydroxy-vitamin D3. Areal and volumetric BMD were assessed by DXA and peripheral quantitative CT (QCT), respectively. RESULTS: Twenty-six patients (13 on each arm) completed the study. Tofacitinib was clinically effective by suppressing DAS28, CRP, and HAQ. This was accompanied by the attenuation of further bone loss. Tofacitinib therapy significantly increased OC, OPG, and vitamin D3, while decreased CTX levels (p < 0.05). Age and multiple bone markers (OC, CTX, P1NP, RANKL) inversely correlated with L2-4 and femoral neck BMD by DXA. CRP, DAS28, and RANKL inversely determined volumetric BMD by QCT. Age, CRP, anti-CCP, and DKK-1 influenced the effects of tofacitinib therapy on BMD changes. CONCLUSIONS: One-year tofacitinib treatment stabilized BMD in RA patients and resulted in a positive balance of bone turnover as indicated by bone biomarkers. Further studies are needed to evaluate the potential beneficial effects of JAK inhibitors on inflammatory bone loss.

Treatment of ankylosing spondylitis with biologics and targeted physical therapy: positive effect on chest pain, diminished chest mobility, and respiratory function.

OBJECTIVE: Biologics are highly effective in ankylosing spondylitis (AS). In this self-controlled study, we assessed the additive value of complex physiotherapy in decreasing chest pain and tenderness and improving respiratory function in AS patients treated with tumor necrosis factor α (TNF-α) inhibitors. PATIENTS AND METHODS: The trial consisted of 2 parts. In study I, clinical data of AS patients with (n=55) or without biological therapy (n=20) were retrospectively analyzed and compared. Anthropometrical data, duration since diagnosis and patient assessment of disease activity, pain intensity, tender points, sacroiliac joint involvement determined by X-ray, functional condition, and physical activity level were recorded. Subjective, functional, and physical tests were performed. In study II, 10 voluntary patients (6 men and 4 women, age 52.4 ± 13.6 years) with definite AS and receiving anti-TNF therapy were recruited. It was a prospective, non-randomized physiotherapeutic trial. BASFI (Bath Ankylosing Spondylitis Functional Index), BASDAI (Bath Ankylosing Spondylitis Disease Activity Index), modified Schober Index, occiput-to-wall distance, and fingertip-to-floor distance were evaluated. Forced vital capacity, forced 1-s expiratory volume, peak expiratory flow, and maximum voluntary ventilation were recorded. Furthermore, typical tender points were recorded. A targeted physiotherapy program was conducted twice a week for 12 weeks and all above parameters were recorded at baseline and after 12 weeks. RESULTS: Differences in patient assessment of disease activity (p=0.019) and pain intensity (p=0.017) were found in study I. Pain and tenderness of the thoracic spine were observed in both groups. Back pain without biologic therapy was slightly higher than other group. In study II, we found that patient assessment of disease activity and pain intensity significantly improved after the physical therapy program (p=0.002 and p<0.001). BASFI and BASDAI increased after treatment (p=0.004 and p<0.001). The finger-to-floor distance, chest expansion, and modified Schober index increased (p=0.008, p<0.001, and p=0.031, respectively). The respiratory functional parameters showed a tendency towards improvement. CONCLUSION: AS patients already receiving biological therapy may benefit from additional targeted physiotherapy. Physical therapy may be of important additive value in AS patients being treated with biological. The exercise program presented here showed an improvement in functional parameters as well as spine and chest mobility, thereby enhancing the favorable effects of biological therapy.